caffeine

Research Excerpts

Overview

Caffeine is a central nervous system stimulant and acts in the brain through adenosine receptors, influencing attention, alertness, and anxiety. It is a widely consumed psychostimulant with several mechanisms of action and various positive and negative effects on organisms.

Excerpt	Reference	Relevance
"Caffeine (CF) is a member of the methylxanthine family with numerous biological activities, which may contribute to the prevention of human disease but also may be potentially harmful. "	( Studies on the interaction of caffeine with bovine hemoglobin. Wang, YQ; Zhang, HM; Zhou, QH, 2009)	2.08
"Caffeine is a neuroactive compound that affects both the behaviour and physiology of several animal species, from humans to insects."	( Cascading effects of caffeine intake by primary consumers to the upper trophic level. Hance, T; Tougeron, K, 2022)	1.76
"Caffeine is a widely used nootropic drug, but its effects on memory in healthy participants have not been sufficiently evaluated. "	( How does caffeine influence memory? Drug, experimental, and demographic factors. Madan, CR; Zhang, RC, 2021)	2.48
"Caffeine is a widely consumed psychostimulant with several mechanisms of action and various positive and negative effects on organisms. "	( Simultaneous determination of caffeine and its metabolites in rat plasma by UHPLC-MS/MS. Kertys, M; Kmeťová, K; Maráková, K; Mokrý, J; Pršo, K; Žideková, N, 2021)	2.35
"Caffeine is a contaminant frequently detected in water bodies. "	( Sublethal effects of environmental concentrations of caffeine on a neotropical freshwater fish. Almeida, RM; Barros, N; Bialetzki, A; Dos Santos, JA; Lobo, H; Quadra, GR; Reis, JL; Rocha, VN; Roland, F; Soranço, L, 2022)	2.41
"Caffeine is a central nervous system stimulant and acts in the brain through adenosine receptors, influencing attention, alertness, and anxiety."	( Caffeine-related genes influence anxiety disorders in children and adults with ADHD. Bandeira, CE; Bau, CHD; Contini, V; da Silva, BS; Dresch, F; Fraporti, TT; Genro, JP; Grevet, EH; Hutz, MH; Martins-Silva, T; Rohde, LA; Rovaris, DL; Tovo-Rodrigues, L, 2022)	2.89
"Caffeine is a commonly consumed psychoactive substance whose addictive potential has long been reported. "	( UPLC-MS/MS method for the simultaneous quantification of caffeine and illicit psychoactive drugs in hair using a single-step high-speed grinding extraction - Insights into a cut-off value for caffeine abuse. Chen, J; Di, B; Jiang, S; Qiao, H; Su, M; Zhong, Y, 2022)	2.41
"Caffeine is an antagonist of adenosine receptors and may enhance antidepressant effects through downstream dopaminergic targets."	( Habitual caffeine consumption moderates the antidepressant effect of dorsomedial intermittent theta-burst transcranial magnetic stimulation. Bodén, R; Frick, A; Persson, J, 2021)	1.76
"d9-Caffeine is a deuterated isotopologue of caffeine with the nine hydrogens contained in the 1, 3, and 7 methyl groups of caffeine substituted with deuterium."	( Pharmacokinetic, pharmacological, and genotoxic evaluation of deuterated caffeine. Burdock, GA; Parente, RM; Sippy, BC; Tarantino, PM, 2022)	1.47
"Caffeine serves as a neurochemical model to demonstrate neural signal transmission."	( Electrophysiological Monitoring of Neurochemical-Based Neural Signal Transmission in a Human Brain-Spinal Cord Assembloid. Cho, HY; Choi, JW; Ha, T; Lee, SN; Park, SJ; Son, J, 2022)	1.44
"Caffeine acts as a repellent agent against rice pathogens."	( Intracellular Ca Cho, MH; Kim, KM; Lee, GS; Lee, SW; Lee, TH; Lim, H; Park, JC; Sano, H; Win, KTYS; Yoo, Y; Yun, S, 2022)	1.44
"Caffeine is a characteristic bioactive compound in tea and coffee plants, which is synthesized and accumulated extensively in leaves and seeds. "	( Metabolite Profiling and Transcriptome Analysis Revealed the Conserved Transcriptional Regulation Mechanism of Caffeine Biosynthesis in Tea and Coffee Plants. Chi, N; Fu, J; Guo, T; Inayat, MA; Li, F; Li, L; Li, P; Ma, S; Shen, Y; Tang, D; Ye, Z; Zhang, Y; Zhao, J; Zhou, Q, 2022)	2.38
"Caffeine is a common stressor, and its consumption during pregnancy is widespread."	( Differential expression of placental 11β-HSD2 induced by high maternal glucocorticoid exposure mediates sex differences in placental and fetal development. Fang, M; Ge, C; Wang, H; Yu, P; Zhang, Y; Zhou, J, 2022)	1.44
"Caffeine is a psycho-active stimulant that can improve physical and cognitive performance. "	( Acute caffeine supplementation and live match-play performance in team-sports: A systematic review (2000-2021). Arguedas-Soley, A; Betts, J; Hengist, A; Townsend, I, 2022)	2.64
"Caffeine is a worldwide popularly consumed constituent in foods that can exert physiological effects. "	( The Inverted U-Shaped Association of Caffeine Intake with Serum Uric Acid in U.S. Adults. Geng, Q; Jiang, C; Liu, A; Liu, Q; Ma, H; Yin, H; Zhou, H, 2022)	2.44
"Caffeine is a widely consumed high-potency antioxidant and may be of interest for the prevention of the disease."	( The human lens: An antioxidant-dependent tissue revealed by the role of caffeine. Findl, O; Kronschläger, M; Ruiss, M, 2022)	1.68
"Caffeine is a naturally occurring alkaloid and it is metabolized to paraxanthine, theophylline and theobromine. "	( Simultaneous quantification of caffeine and its main metabolites by gas chromatography mass spectrometry in horse urine. Dirikolu, L; Göktaş, EF; Güneş, E; Kabil, E; Yatanaslan, L, 2022)	2.45
"Caffeine is a psychostimulant substance that is mostly used to prevent fatigue, increase alertness, and ameliorate sleep loss situations. "	( Chronic caffeine consumption improves the acute sleep deprivation-induced spatial memory impairment while altering N-methyl-D-aspartate receptor subunit expression in male rats. Cevik, OS; Keloglan, SM; Sahin, L, 2022)	2.6
"Caffeine is a routinely prescribed pharmacological active compound in neonatal intensive care units (NICU) for treating apnea of prematurity (AOP), which also decreases the risk of bronchopulmonary dysplasia and cerebral palsy in neonates. "	( Relationship of caffeine regimen with osteopenia of prematurity in preterm neonates: a cohort retrospective study. Ali, A; Ambreen, G; Hussain, K; Khan, M; Khan, MA; Khan, WA; Kumar, M; Naz, F; Salat, MS; Saleem, SM; Sohail, S, 2022)	2.51
"Caffeine is a psychoactive compound used widely to enhance cognitive functions in human or animal studies. "	( Effect of intranasal administration of caffeine on mPFC ischemia‑induced cognitive impairment in BALB/c mice. Farajdokht, F; Farhoudi, M; Farokhi-Sisakht, F; Kahfi-Ghaneh, R; Mahmoudi, J; Sadigh-Eteghad, S, 2022)	2.43
"Caffeine is a psychoactive substance used worldwide. "	( Caffeine intoxication: Behavioral and electrocorticographic patterns in Wistar rats. Araújo, DB; Azevedo, JEC; Barbas, LAL; da Silva, ALM; Hamoy, AO; Hamoy, M; Lopes, DCF; Lopez, MEC; Mello, VJ; Nascimento, CP; Pereira, RG; Rodrigues, SF; Vieira, LR, 2022)	3.61
"Caffeine consumption is a risk factor for chronic daily headache but few studies have addressed relationships between pediatric patient caffeine levels and headache severity. "	( Caffeine consumption as a risk factor for childhood and adolescence migraine. Goda, H; Hikita, T; Ito, K; Kudo, T; Ogawa, Y, 2023)	3.8
"Caffeine content is a crucial attribute of coffee. "	( Variability of caffeine content in green and roasted Árvay, J; Belej, Ľ; Bobko, M; Bobková, A; Capcarová, M; Demianová, A; Hegedűsová, A; Jurčaga, L; Lidiková, J; Poláková, K, 2022)	2.52
"Caffeine is a central nervous system stimulant. "	( Assessment of caffeine consumption behavior among Jazan University students in the south of Saudi Arabia: A cross-sectional study. Abuageelah, BM; Alfaifi, AJ; Alfaifi, MH; Alfaifi, SM; Alsam, HA; Gosadi, IM; Shajeri, MA; Tawhari, FY, 2022)	2.52
"Caffeine is a kind of psychostimulant that naturally exist in foods. "	( Trends of caffeine intake from food and beverage among Chinese adults: 2004-2018. Song, Y; Sui, H; Xiao, X; Yang, D; Ye, C; Yong, L, 2023)	2.76
"Caffeine is a widely consumed stimulant, known for its positive effects on physical and mental performance. "	( Caffeine-Supplemented Diet Prevents Fatigue-Like Behavior in Tumor-Bearing Mice. Ferdaos, N; Harada, A; Horaguchi, T; Kasai, S; Masuda, E; Yoshizawa, K, 2023)	3.8
"Caffeine is a natural compound found in plant seeds that after consumption by humans effects the central nervous system as well as the cardiovascular system. "	( Caffeine Biodegradation by Cytochrome P450 1A2. What Determines the Product Distributions? de Visser, SP; Mokkawes, T, 2023)	3.8
"Caffeine is a widely consumed substance, and there is a discussion about its effects when ingested by women during pregnancy and lactation. "	( Genotoxic effects of caffeine in female mice exposed during pregnancy and lactation period and their offspring. Bahia Franca, I; Da Silva, J; Lummertz Magenis, M; Martins Longaretti, L; Moraes de Andrade, V; Paganini Damiani, A; Ricardo Cantareli da Silva, A; Rodrigues Boeck, C; Souza de Marcos, P, 2023)	2.67
"Caffeine (CAF) is an alkaloid, which acts as a central nervous system (CNS) stimulant drug. "	( Integrative approach to elucidate the embryological effects of caffeine in Cyprinus carpio: Bioconcentration and alteration of oxidative stress-related gene expression patterns. Casas-Hinojosa, I; Dublán-García, O; Elizalde-Velázquez, GA; Galar-Martínez, M; Gómez-Oliván, LM; Gracía-Medina, S; Gutierrez-Noya, VM; Hernández-Navarro, MD; Islas-Flores, H; Orozco-Hernández, JM; Rosales-Pérez, KE, 2023)	2.59
"Caffeine is a very common kind of nervous stimulant, and it is primarily metabolized by Cytochrome P450 1A2 (CYP1A2) in the human body. "	( Active Binding Modes of Caffeine with Cytochrome P450 1A2 Determine Its Metabolite Profiles. Lyu, L; Sun, M; Zheng, Q, 2023)	2.66
"Caffeine is an emerging contaminant in aquatic environments. "	( Development of a trace quantitative method to investigate caffeine distribution in the Yellow and Bohai Seas, China, and assessment of its potential neurotoxic effect on fish larvae. Li, K; Li, Y; Lin, A; Lu, Z; Niu, D; Tang, J; Yan, Z; Yang, X; Zhang, H; Zhang, T; Zhao, J; Zhao, X, 2023)	2.6
"Caffeine is a trimethylxanthine found in coffee and several other foods and beverages. "	( Caffeine and sport. Barreto, G; da Costa, LR; de Souza, RAS; Marticorena, FM; Saunders, B, 2023)	3.8
"Caffeine is an adenosine receptor antagonist."	( Caffeine-folic acid-loaded-chitosan nanoparticles combined with methotrexate as a novel HepG2 immunotherapy targeting adenosine A2A receptor downstream cascade. Gaber, M; Ghareeb, D; Hamed, A; Hamed, M; Mohamed, TM; Nofal, MS, 2023)	3.07
"Caffeine is a psychoactive substance widely consumed worldwide, mainly via sources such as coffee and tea. "	( Caffeine Intake, Plasma Caffeine Level, and Kidney Function: A Mendelian Randomization Study. Cronje, HT; de La Harpe, R; Gill, D; Giontella, A; Larsson, SC; Woolf, B; Zagkos, L, 2023)	3.8
"Caffeine is a natural component that affects the cardiovascular system, while the mechanisms of its effects are not fully established."	( The effects of caffeine supplementation on blood pressure in adults: A systematic review and dose-response meta-analysis. Abbas-Hashemi, SA; Asbaghi, O; Hosseininasab, D; Rastgoo, S; Shiraseb, F, 2023)	1.98
"Caffeine is a powerful metabolic stimulant in the skeletal muscle that has ergogenic effects, including enhanced muscle power output and endurance capacity."	( The Effects of Caffeine on Metabolomic Responses to Muscle Contraction in Rat Skeletal Muscle. Egawa, T; Hayashi, T; Tsuda, S, 2019)	1.59
"Caffeine is a popular and widely consumed sporting ergogenic aid. "	( Are low doses of caffeine as ergogenic as higher doses? A critical review highlighting the need for comparison with current best practice in caffeine research. Kiely, J; Pickering, C, )	1.91
"Caffeine is a well-established ergogenic aid, with its performance-enhancing effects replicated across a variety of exercise types. "	( Are caffeine's performance-enhancing effects partially driven by its bitter taste? Pickering, C, 2019)	2.51
"caffeine is a major constituent in numerous foods, beverages, dietary supplements and medications.Angelica dahurica (Hoffm.) Benth. "	( Caffeine/Angelica dahurica and caffeine/Salvia miltiorrhiza metabolic inhibition in humans: In vitro and in vivo studies. Alehaideb, ZI; Law, FCP; Sheriffdeen, MM, 2019)	3.4
"Caffeine is a well-established ergogenic aid, with its performance-enhancing effects demonstrated across a wide variety of exercise modalities. "	( Is Coffee a Useful Source of Caffeine Preexercise? Grgic, J; Pickering, C, 2020)	2.29
"Caffeine is a popular nutritional supplement among athletes. "	( Effect of caffeine supplementation on exercise performance, power, markers of muscle damage, and perceived exertion in trained CrossFit men: a randomized, double-blind, placebo-controlled crossover trial. Bottaro, M; Dos Santos, WD; Fogaça, LJ; Gentil, P; Mota, JF; Naves, JP; Pimentel, GD; Santos, SL; Soares, RC, 2020)	2.4
"Caffeine is a naturally occurring alkaloid, where its major consumption occurs with beverages such as coffee, soft drinks and tea. "	( Evolutionary engineering and molecular characterization of a caffeine-resistant Saccharomyces cerevisiae strain. Arslan, M; Çakar, ZP; Holyavkin, C; Kısakesen, Hİ; Sürmeli, Y; Topaloğlu, A, 2019)	2.2
"Caffeine is a well-established ergogenic aid, although research to date has predominantly focused on anhydrous caffeine, and in men. "	( Coffee Ingestion Improves 5 km Cycling Performance in Men and Women by a Similar Magnitude. Clarke, ND; Kirwan, NA; Richardson, DL, 2019)	1.96
"Caffeine is a popular psychostimulant, which is frequently consumed with ethanol. "	( Caffeine Potentiates Ethanol-Induced Neurotoxicity Through mTOR/p70S6K/4E-BP1 Inhibition in SH-SY5Y Cells. Dharmasaroja, P; Sangaunchom, P, )	3.02
"Caffeine, which is a competitive inhibitor of adenosine receptors, is commonly used as treatment for preterm apnoea in clinical settings."	( Defining a Time Window for Neuroprotection and Glia Modulation by Caffeine After Neonatal Hypoxia-Ischaemia. Ådén, U; Blomgren, K; Bocchetta, E; Di Martino, E; Harris, RA; Mukai, T; Tsuji, S, 2020)	1.52
"Caffeine seems to be a valid bitter compound for regional testing using taste strips and may be used alternatively to quinine."	( Bitter Taste Perception of the Human Tongue Mediated by Quinine and Caffeine Impregnated Taste Strips. Besser, G; Liu, DT; Mueller, CA; Oeller, F; Renner, B, 2020)	2.24
"Caffeine is a psychostimulant and excessive use predisposes to cell damage and neurotoxicity."	( Neferine and lianzixin extracts have protective effects on undifferentiated caffeine-damaged PC12 cells. Chen, J; Jiang, Y; Liu, B; Liu, M; Liu, S; Tang, M, 2020)	1.51
"Caffeine is a major component of xanthine alkaloids and commonly consumed in many popular beverages. "	( Identification and characterization of N9-methyltransferase involved in converting caffeine into non-stimulatory theacrine in tea. Abe, I; Cao, ZQ; Ding, K; Duan, WJ; Gong, HB; He, RR; Hu, D; Kurihara, H; Li, YF; Lu, X; Ouyang, SH; Sun, WY; Tan, L; Wang, Y; Xie, C; Xie, G; Zhang, YH; Zhang, ZM, 2020)	2.23
"Caffeine is a common treatment for neonatal intensive care management of the developmental complication of apnea of prematurity in preterm infants. "	( Caffeine for the Treatment of Apnea in the Neonatal Intensive Care Unit: A Systematic Overview of Meta-Analyses. Abushanab, D; Al-Badriyeh, D; Al-Shaibi, S; Alhersh, E, 2020)	3.44
"Caffeine (CA) is a common xanthine alkaloid found in tea leaves, coffee beans, and other natural plants, and is the most widely used psychotropic substance in the world. "	( Detection of caffeine and its main metabolites for early diagnosis of Parkinson's disease using micellar electrokinetic capillary chromatography. Han, Y; Hu, S; Shi, H; Sun, Z; Wang, X; Xu, X; Xun, L; Yang, S, 2020)	2.37
"Caffeine is a drug used to treat apnea in premature infants."	( Caffeine prevents hyperoxia-induced lung injury in neonatal mice through NLRP3 inflammasome and NF-κB pathway. Chen, S; Du, L; Li, C; Wu, Q; Zhong, D, 2020)	2.72
"Caffeine is a naturally occurring plant alkaloid and is found in plant constituents such as coffee and cocoa beans, tea leaves, guarana berries and the kola nut [...]."	( Caffeine and Doping-What Have We Learned since 2004. Diel, P, 2020)	3.44
"Caffeine, which is a known neuroprotectant, can potentially act as an adjunct to minimise adverse effects of L-DOPA."	( Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Manalo, RVM; Medina, PMB, 2020)	2.72
"Caffeine citrate is a commonly used methylxanthine for pharmacologic treatment of apnea of prematurity. "	( Population pharmacokinetic study of caffeine citrate in Chinese premature infants with apnea. Di, X; Fan, J; Guo, A; Hu, X; Huang, L; Xie, H; Xue, J; Zhao, P; Zhu, Z, 2020)	2.28
"Caffeine is a habit-forming substance consumed daily by the majority of pregnant women. "	( Maternal caffeine consumption and pregnancy outcomes: a narrative review with implications for advice to mothers and mothers-to-be. James, JE, 2021)	2.48
"Caffeine is an exercise performance enhancer widely used by individuals engaged in training or competition under heat-stressed conditions. "	( Caffeine Exacerbates Hyperventilation and Reductions in Cerebral Blood Flow in Physically Fit Men Exercising in the Heat. Amano, T; Dobashi, K; Fujii, N; Fujimoto, T; Matsutake, R; Nishiyasu, T; Watanabe, K; Yinhang, C, 2021)	3.51
"Caffeine is an adenosine receptor antagonist with effects on the brain, lung and other systems."	( Neurodevelopmental outcomes after neonatal caffeine therapy. Grunau, RE; Synnes, A, 2020)	1.54
"Caffeine is a common stimulant consumed daily worldwide and available in a wide variety of over-the-counter formulations. "	( The importance of early use of beta blockers and gastric decontamination in caffeine overdose: A case report. Ajjampur, K; Subramaniam, A, 2021)	2.29
"Caffeine is an effective treatment for apnea of prematurity and has several important benefits, including decreasing respiratory morbidity and motor impairment. "	( Caffeine for preterm infants: Fixed standard dose, adjustments for age or high dose? Patel, RM; Saroha, V, 2020)	3.44
"Caffeine treatment is a preferred treatment choice."	( Therapy for Apnoea of Prematurity: A Retrospective Study on Effects of Standard Dose and Genetic Variability on Clinical Response to Caffeine Citrate in Chinese Preterm Infants. Chen, F; Cheng, R; Guo, HL; He, X; Jia, WW; Li, L; Liu, Y; Lu, KY; Ni, MM; Qiu, JC; Xu, J, 2021)	1.55
"Caffeine is a common stimulant widely existed in food and has stimulatory effects on the central nervous system, shift-work individuals often rely on caffeine to maintain attention and keep awake. "	( Caffeine-related effects on cognitive performance: Roles of apoptosis in rat hippocampus following sleep deprivation. Huang, P; Huang, X; Li, H; Wang, P; Xie, G, 2021)	3.51
"Caffeine is a well-established ergogenic aid, with its performance-enhancing effects demonstrated across a variety of sports and exercise types. "	( A time and a place: A framework for caffeine periodization throughout the sporting year. Grgic, J; Pickering, C, 2021)	2.34
"Caffeine is a popular ergogenic aid due to its primary physiological effects that occur through antagonism of adenosine receptors in the central nervous system. "	( Novel insights on caffeine supplementation, CYP1A2 genotype, physiological responses and exercise performance. Barreto, G; Grecco, B; Gualano, B; Merola, P; Reis, CEG; Saunders, B, 2021)	2.4
"Caffeine is a widely used dietary stimulant, and cases of caffeine overdoses, sometimes leading to death, are increasing. "	( Suicidal attempt with caffeine overdose treated with dexmedetomidine: a case report. Kitano, T; Noda, T; Okajima, M; Sato, K; Taniguchi, T, 2021)	2.38
"Caffeine is a natural stimulant most commonly found in coffee and tea."	( Caffeine promotes the expression of telomerase reverse transcriptase to regulate cellular senescence and aging. Diao, A; Li, Y; Liu, Z; Niu, X; Tao, L; Zhang, M; Zhang, W; Zhang, Y; Zhao, Q, 2021)	2.79
"Caffeine is a known inhibitor of Clozapine metabolism mediated by inhibition of CYP1A2. "	( Caffeine-clozapine interaction associated with severe toxicity and multiorgan system failure: a case report. Peisah, C; Yartsev, A, 2021)	3.51
"Caffeine is a food supplement widely consumed by athletes, but it has not been established. "	( Caffeine Health Claims on Sports Supplement Labeling. Analytical Assessment According to EFSA Scientific Opinion and International Evidence and Criteria. Estevan Navarro, P; Gil-Izquierdo, A; González-Díaz, C; Jiménez-Alfageme, R; Martínez-Sanz, JM; Medina, S; Perales, A; Sospedra, I, 2021)	3.51
"Caffeine is a plant alkaloid present in food and beverages consumed worldwide. "	( Novel Facet of an Old Dietary Molecule? Direct Influence of Caffeine on Glucose and Biogenic Amine Handling by Human Adipocytes. Ahmed, WH; Boulet, N; Briot, A; Carpéné, C; Henehan, GTM; Kinsella, GK; Les, F; Mercader-Barceló, J; O'Sullivan, J; Ryan, BJ, 2021)	2.31
"Caffeine is an active ingredient found in coffee and energy beverages. "	( Caffeine prevents oxalate-induced epithelial-mesenchymal transition of renal tubular cells by its anti-oxidative property through activation of Nrf2 signaling and suppression of Snail1 transcription factor. Kanlaya, R; Nanthawuttiphan, S; Subkod, C; Thongboonkerd, V, 2021)	3.51
"Caffeine is a commonly used stimulant of the central nervous system that reduces fatigue, increases alertness, and exerts positive effects on emotion through actions on various brain structures. "	( Estrous cycle modulates the anxiogenic effects of caffeine in the elevated plus maze and light/dark box in female rats. Cueto-Escobedo, J; Guillén-Ruiz, G; Hernández-López, F; Herrera-Huerta, EV; Rivera-Aburto, LE; Rodríguez-Landa, JF, 2021)	2.32
"Caffeine is a well-established performance enhancing nutritional supplement in a young healthy population, however far less is known about how its ergogenicity is affected by increasing age. "	( Is the Ergogenicity of Caffeine Affected by Increasing Age? The Direct Effect of a Physiological Concentration of Caffeine on the Power Output of Maximally Stimulated EDL and Diaphragm Muscle Isolated from the Mouse. Cox, VM; Duncan, MJ; James, RS; Tallis, J, 2017)	2.21
"Caffeine is a widely used dietary stimulant that can reverse the effects of fatigue on cognitive, motor and oculomotor function. "	( Caffeine increases the velocity of rapid eye movements in unfatigued humans. Connell, CJW; Gant, N; Hess, RF; Thompson, B; Turuwhenua, J, 2017)	3.34
"Caffeine is a non-selective adenosine antagonist; therefore, it can modulate metabolic pathways in these tissues."	( The perinatal effects of maternal caffeine intake on fetal and neonatal brain levels of testosterone, estradiol, and dihydrotestosterone in rats. Bayrak, S; Erdem, A; Erdogan, G; Ergun, EL; Karaismailoglu, S; Tuncer, M, 2017)	1.46
"Caffeine is a highly catabolic dietary stimulant. "	( Acute high-caffeine exposure increases autophagic flux and reduces protein synthesis in C2C12 skeletal myotubes. Baumgarner, BL; Crocker, CL; Downs, RM; Hughes, MA; Kinsey, ST; Webb, GW, 2017)	2.29
"Caffeine is a known ergogenic aid that could be dosed at 3 mg·kg to maximize benefits of mental alertness while limiting potential side effects."	( Fueling the Triathlete: Evidence-Based Practical Advice for Athletes of All Levels. Getzin, AR; Harkins, M; Milner, C, )	0.85
"Caffeine is a psychostimulant frequently consumed by adults and children, often in combination with high levels of sugar. "	( The behavioral effects of chronic sugar and/or caffeine consumption in adult and adolescent rats. Cornish, JL; Franklin, JL; Homewood, J; Wearne, TA, 2017)	2.15
"Caffeine is a widely used psychostimulant that is associated with increased acetylcholine levels in mammalian brain and acetycholinesterase antagonism. "	( Acute caffeine ingestion affects surround suppression of perceived contrast. Hew, SA; Ly, J; McKendrick, AM; Nguyen, BN; Shin, HY; Wong, JC; Yeung, E, 2018)	2.4
"Caffeine is a widely consumed psychoactive substance, but little is known about the effects of caffeine stimulation on global gene expression changes in neurons. "	( Acute doses of caffeine shift nervous system cell expression profiles toward promotion of neuronal projection growth. Bieder, A; Daub, CO; Einarsdottir, E; Falk, A; Fredholm, BB; Katayama, S; Kere, J; Mileti, E; Raman, A; Tapia-Páez, I; Yu, NY, 2017)	2.25
"Caffeine is an emerging contaminant considered to be an indicator of human contamination that has been widely detected in various aquatic systems, especially in continental waters. "	( Does the presence of caffeine in the marine environment represent an environmental risk? A regional and global study. Barceló, D; Cáceres, N; Dafouz, R; de Miguel, ÁG; López de Alda, M; Mastroianni, N; Rodríguez-Gil, JL; Valcárcel, Y, 2018)	2.24
"Caffeine is an adenosine receptor antagonist and a possible cause of inadequate stress perfusion. "	( Disagreement between splenic switch-off and myocardial T1-mapping after caffeine intake. Kaandorp, TAM; Kuijpers, D; Oudkerk, M; van Assen, M; van der Harst, P; van Dijk, R; van Dijkman, PRM; Vliegenthart, R, 2018)	2.16
"Caffeine is a methylxanthine derived from plant foods such as coffee beans and tea leaves, and has multiple biological activities against physiological response and several diseases. "	( Caffeine-Stimulated Intestinal Epithelial Cells Suppress Lipid Accumulation in Adipocytes. Ashida, H; Harada, K; Mitani, T; Nagano, T; Yamashita, Y, 2017)	3.34
"Caffeine is a substance present in several foods and drinks of common western diet. "	( Different effects of caffeine on behavioral neurophenotypes of two zebrafish populations. Ardais, AP; Costa, FV; Fontana, BD; Porciúncula, LO; Quadros, VA; Rosa, LV; Rosemberg, DB, 2018)	2.24
"Caffeine is a nonselective competitive inhibitor of adenosine2A-receptors, which might hamper the vasodilator effect of adenosine stress, potentially yielding false-negative results."	( Effects of caffeine on the detection of ischemia in patients undergoing adenosine stress cardiovascular magnetic resonance imaging. Abu-Zaid, E; Birkmeier, S; Greulich, S; Kaesemann, P; Mahrholdt, H; Sechtem, U; Seitz, A; Vecchio, F, 2017)	1.57
"Caffeine is a molecule free of serious adverse effects when consumed at low doses."	( Severe Sympathomimetic Toxidrome in a French Soldier: How Caffeine Overdose Can Lead to Severe Consequences. Delacour, H; Dubost, C; Lahutte, B; Laitselart, P; Plantamura, J; Saguin, E, 2018)	1.45
"Caffeine is a common psychoactive substance with a documented addictive potential. "	( Caffeine use disorder: An item-response theory analysis of proposed DSM-5 criteria. Ágoston, C; Demetrovics, Z; Richman, MJ; Urbán, R, 2018)	3.37
"Caffeine is a respiratory stimulant used during removal of infants from ventilation but has shown surprising long-term benefits, leading to consideration as a therapy for HI of prematurity."	( Behavioral and neuroanatomical outcomes in a rat model of preterm hypoxic-ischemic brain Injury: Effects of caffeine and hypothermia. Fitch, RH; Potter, M; Rosenkrantz, T, 2018)	1.41
"Caffeine is a widely consumed pharmacologically active product. "	( Caffeine inhibits STAT1 signaling and downregulates inflammatory pathways involved in autoimmunity. Iris, M; Sawalha, AH; Tsou, PS, 2018)	3.37
"Caffeine is a widely used ergogenic aid with most research suggesting it confers the greatest effects during endurance activities. "	( The Effect of Acute Caffeine Ingestion on Endurance Performance: A Systematic Review and Meta-Analysis. Ali, A; Rutherfurd-Markwick, KJ; Southward, K, 2018)	2.25
"Caffeine is a common active adulterant found in illicit drugs of abuse, including coca paste (CP). "	( Caffeine as an adulterant of coca paste seized samples: preclinical study on the rat sleep-wake cycle. Falconi, A; Lagos, P; Schwarzkopf, N; Scorza, C; Torterolo, P, 2018)	3.37
"Caffeine is a well-established ergogenic aid, demonstrated to enhance performance across a wide range of capacities through a variety of mechanisms. "	( What Should We Do About Habitual Caffeine Use in Athletes? Kiely, J; Pickering, C, 2019)	2.24
"Caffeine is a common pharmaceutical and personal care product pollutant in wastewater. "	( Chemical nanosensors based on molecularly-imprinted polymers doped with silver nanoparticles for the rapid detection of caffeine in wastewater. Hu, R; Lu, F; Tang, R; Xu, J, 2018)	2.13
"Caffeine is a central nervous system stimulant occurring naturally in some foods and used to treat primary apnoea in premature babies."	( Effects of maternal caffeine consumption on the breastfed child: a systematic review. Bird, S; Brown, LJ; Chen, YF; McCreedy, A; Shaw-Stewart, J, 2018)	1.53
"Caffeine is a substance that is consumed worldwide, and it may exert neuroprotective effects against various cerebral insults, including neurotrauma, which is the most prevalent injury among military personnel. "	( Caffeine attenuates brain injury but increases mortality induced by high-intensity blast wave exposure. Chen, JF; Chen, X; Li, P; Liu, D; Ning, YL; Peng, Y; Tian, HK; Wang, ZG; Yang, N; Zhang, XZ; Zhao, Y; Zhao, ZA; Zhou, YG, 2019)	3.4
"Caffeine is a widely consumed stimulant, and caffeine-containing products are increasingly available on the market. "	( Evaluation of a 24-Hour Caffeine Intake Assessment Compared with Urinary Biomarkers of Caffeine Intake among Young Adults in Canada. Acton, RB; Hammond, D; Kirkpatrick, SI; Pao, CI; Reid, JL; Rybak, ME; Vanderlee, L; White, CM, 2018)	2.23
"Caffeine is a widely studied psychostimulant, even though its exact effect on brain activity remains to be elucidated. "	( The effect of caffeine on cerebral metabolism during alpha-chloralose anesthesia differs from isoflurane anesthesia in the rat brain. Chiu, H; Chung, YH; Huang, CW; Peng, SL; Shen, WC; Shih, CT; Wu, CY, 2019)	2.32
"Caffeine is a bioactive compound worldwide consumed with effect into the brain. "	( Caffeine Neuroprotection Decreases A2A Adenosine Receptor Content in Aged Mice. Alves, MC; Boeck, CR; Damiani, AP; de Abreu, LL; de Andrade, VM; Garcez, ML; Pacheco, R; Rodrigues, L, 2019)	3.4
"Caffeine is a crucial secondary metabolic product in tea plants. "	( Caffeine Content and Related Gene Expression: Novel Insight into Caffeine Metabolism in Camellia Plants Containing Low, Normal, and High Caffeine Concentrations. Chen, LB; Deng, WW; Han, J; Lu, M; Zhang, J; Zhang, ZZ; Zhu, B, 2019)	3.4
"Caffeine is a psychoactive substance that may affect the normal course of pregnancy, therefore its intake during that time should not exceed 200 mg/day. "	( Caffeine Intake During Pregnancy and Neonatal Anthropometric Parameters. Jarosz, M; Wierzejska, R; Wojda, B, 2019)	3.4
"Caffeine is a widely utilized performance-enhancing supplement used by athletes and non-athletes alike. "	( Caffeine and Exercise: What Next? Grgic, J; Pickering, C, 2019)	3.4
"Caffeine is a compound that can exert physiological-beneficial effects in the organism. "	( Genotoxic effect of caffeine in Yarrowia lipolytica cells deficient in DNA repair mechanisms. Arredondo-Mendoza, GI; Campos-Góngora, E; Jiménez-Salas, Z; Larriba-Calle, G; Quiñones-González, CA; Ruiz-Herrera, J, 2019)	2.28
"Caffeine is a secondary plant metabolite found in some nectars that affects foraging in pollinators."	( Resource profitability, but not caffeine, affects individual and collective foraging in the stingless bee Grüter, C; Nascimento, F; Peng, T; Segers, FHID, 2019)	1.52
"Caffeine is a methylxanthine with multiple actions in vascular smooth muscle cells (VSMCs), including the increase in the intracellular Ca"	( Activation of Ca Cortes, SF; Garcia, DCG; Lemos, VS; Lopes, MJ; Mbiakop, UC, 2019)	1.96
"Caffeine is a competitive antagonist of adenosine."	( Impact of caffeine on myocardial perfusion reserve assessed by semiquantitative adenosine stress perfusion cardiovascular magnetic resonance. Bekeredjian, R; Chatzitofi, M; Greulich, S; Kaesemann, P; Löbig, S; Mahrholdt, H; Sechtem, U; Seitz, A; Tauscher, G, 2019)	1.64
"Caffeine is a widely used inhibitor of the protein kinases that play a central role in the DNA damage response. "	( Caffeine suppresses homologous recombination through interference with RAD51-mediated joint molecule formation. Essers, J; Kanaar, R; Ristic, D; Sanchez, H; van Rossum-Fikkert, SE; Vidic, I; Wyman, C; Zelensky, AN, 2013)	3.28
"Caffeine is an alkaloid with a stimulant effect in the body. "	( Caffeine inhibits acetylcholinesterase, but not butyrylcholinesterase. Dobes, P; Pohanka, M, 2013)	3.28
"Caffeine is a commonly used stimulant thought to have ergogenic properties. "	( Acute and chronic caffeine administration increases physical activity in sedentary adults. Panek, LM; Schrader, P; Temple, JL, 2013)	2.17
"Caffeine acts as a central nervous stimulant by blocking A1 and A2A adenosine receptors. "	( Is dietary caffeine involved in seizure precipitation? Bråthen, G; Brodtkorb, E; Helde, G; Reimers, A; Samsonsen, C, 2013)	2.22
"Caffeine is a highly consumed psychoactive substance present in our daily drinks. "	( Inhibition of parathyroid hormone secretion by caffeine in human parathyroid cells. Bränström, R; Farnebo, LO; Larsson, C; Lu, M, 2013)	2.09
"Caffeine acts as a MAO inhibitor with Ki values of 0.70 mM and 3.83 mM for the inhibition of MAO-A and MAO-B, respectively. "	( The interactions of caffeine with monoamine oxidase. Petzer, A; Petzer, JP; Pienaar, A, 2013)	2.16
"Caffeine is a substance that has been used in our society for generations, primarily for its effects on the central nervous system that causes wakefulness. "	( Caffeine and glucose homeostasis during rest and exercise in diabetes mellitus. Riddell, MC; Zaharieva, DP, 2013)	3.28
"Caffeine is a central nervous system stimulant that is consumed by large numbers of people on a routine basis, usually in the form of coffee or tea. "	( Fatal caffeine overdose: a case report and review of literature. Hanly, MG; Jabbar, SB, 2013)	2.31
"Caffeine is a nonspecific adenosine receptor antagonist used in premature neonates to treat apnea of prematurity. "	( Caffeine induces alveolar apoptosis in the hyperoxia-exposed developing mouse lung. Dayanim, S; Grewal, S; Londhe, VA; Lopez, B; Maisonet, TM, 2014)	3.29
"Caffeine is a widely consumed substance affecting the metabolism of adenosine and cellular metabolism of calcium. "	( The effect of caffeine on hearing in a guinea pig model of acoustic trauma. Daniel, SJ; Gasbarrino, K; Mujica-Mota, MA; Rappaport, JM; Shapiro, RS, )	1.93
"Caffeine is a naturally occurring methylxanthine that acts as a non-selective adenosine receptor antagonist. "	( Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway. Edling, CE; Falasca, M; Ghonaim, R; Maffucci, T; Selvaggi, F, 2014)	3.29
"Caffeine is a methylxanthine known as a non-selective inhibitor of A2A and A1 adenosine receptors in the brain and shown to be a neuroprotective drug."	( Caffeine neuroprotective effects on 6-OHDA-lesioned rats are mediated by several factors, including pro-inflammatory cytokines and histone deacetylase inhibitions. Cavalheiro, EA; Cerqueira, GS; Correia, AO; de Barros Viana, GS; de Castro Brito, GA; Machado-Filho, JA; Montenegro, AB; Naffah-Mazzacoratti, Mda G; Neves, KR; Nobre, ME, 2014)	2.57
"Caffeine is a commonly consumed substance that has been thought to play a role in the development of tinnitus, but prospective data are lacking. "	( A prospective study of caffeine intake and risk of incident tinnitus. Curhan, GC; Curhan, SG; Glicksman, JT, 2014)	2.16
"Caffeine is a psychostimulant drug that blocks adenosine A₁ and A₂A receptors (A₁Rs and A₂ARs). "	( Sensorimotor gating is disrupted by acute but not chronic systemic exposure to caffeine in mice. Dubroqua, S; Singer, P; Yee, BK, 2014)	2.07
"Caffeine is an interesting compound showing anticancer and protective effects upon topical administration, although its penetration through the skin is compromised by its hydrophilicity."	( Design of solid lipid nanoparticles for caffeine topical administration. Bonina, F; Curreri, S; Offerta, A; Perrotta, RE; Puglia, C; Tarico, MS; Tirendi, GG, 2016)	1.42
"Caffeine is a secondary metabolite of tea and coffee plants. "	( The effects of caffeine on the cholinergic system. Pohanka, M, 2014)	2.2
"Caffeine is an ergogenic aid widely used before and during prolonged exercise. "	( Ingestion of a moderately high caffeine dose before exercise increases postexercise energy expenditure. Del Coso, J; Fernández-Elías, VE; Hamouti, N; Mora-Rodríguez, R; Muñoz, G; Muñoz-Guerra, J; Ortega, JF, 2015)	2.15
"The caffeine in coffee is a bioactive compound with stimulatory effects on the central nervous system and a positive effect on long-term memory."	( Impact of caffeine and coffee on our health. Gonzalez de Mejia, E; Ramirez-Mares, MV, 2014)	1.29
"Caffeine is a major component of coffee and is used widely in food and beverage industries."	( Metabolic engineering of Saccharomyces cerevisiae for caffeine and theobromine production. Bhuiya, MW; Deng, W; Han, J; Jin, L; Li, M; Liu, X; Wang, M; Yu, O; Zhang, Z, 2014)	1.37
"Caffeine is a metabolite of great economic importance, especially in coffee, where it influences the sensorial and physiological impacts of the beverage. "	( Differential regulation of caffeine metabolism in Coffea arabica (Arabica) and Coffea canephora (Robusta). Bedon, L; Husson, J; Lepelley, M; Mathieu, G; Michaux, S; Mueller, L; Perrois, C; Privat, I; Strickler, SR, 2015)	2.16
"Caffeine is a safe, rapidly absorbable molecule that can be linked to other compounds to improve their cell permeability."	( Desferrioxamine-caffeine (DFCAF) as a cell permeant moderator of the oxidative stress caused by iron overload. Alta, EC; Espósito, BP; Goswami, D; Machini, MT; Nomura, CS; Silvestre, DM, 2014)	1.47
"Caffeine is a commonly found ingredient in many beverages. "	( School pupils and university students surveyed for drinking beverages containing caffeine. Górnicka, M; Kaniewska, E; Kossakowska, K; Pierzynowska, J; Woźniak, A, 2014)	2.07
"Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. "	( Exercise and sport performance with low doses of caffeine. Spriet, LL, 2014)	2.1
"Caffeine is a metabolite from coffee genus and some other plants. "	( Caffeine alters oxidative homeostasis in the body of BALB/c mice. Pohanka, M, 2014)	3.29
"Caffeine acts as a weak psychostimulant and is known to cause trouble with sleeping. "	( Unexpected occurrence of caffeine in sleep-inducing herbal teas. Bieri, S; Christen, P; Edder, P; Mathona, C, 2014)	2.15
"Caffeine is an easily available drug which is generally regarded as being safe. "	( Caffeine intoxication successfully treated by hemoperfusion and hemodialysis. Fukasawa, H; Furuya, R; Ishigaki, S; Kinoshita-Katahashi, N; Kumagai, H; Yasuda, H, 2014)	3.29
"Caffeine is a widely used nutritional supplement which has been shown to enhance both physical and cognitive performance in younger adults. "	( The effect of caffeine ingestion on functional performance in older adults. Clarke, ND; Duncan, MJ; Guimarães-Ferreira, L; Leddington Wright, S; Tallis, J, 2014)	2.21
"Caffeine is a widely consumed substance present in several beverages. "	( Dose-dependent effects of caffeine in human Sertoli cells metabolism and oxidative profile: relevance for male fertility. Alves, MG; Barros, A; Bernardino, RL; Dias, TR; Martins, AD; Moreira, AC; Oliveira, PF; Silva, BM; Silva, J; Sousa, M, 2015)	2.16
"Caffeine is a common additive to SSB, and through dependence effects, it has the potential to promote the consumption of caffeine-containing foods."	( Caffeine increases sugar-sweetened beverage consumption in a free-living population: a randomised controlled trial. Keast, RS; Riddell, LJ; Sayompark, D; Swinburn, BA; Whitelock, S, 2015)	2.58
"Caffeine is a common additive in formulated beverages, including sugar-sweetened beverages. "	( Australian children's consumption of caffeinated, formulated beverages: a cross-sectional analysis. Beckford, K; Grimes, CA; Riddell, LJ, 2015)	1.86
"Caffeine is an active alkaloid that can cause damage to bones in formation during prenatal life into adulthood. "	( Osteogenic potential of osteoblasts from neonatal rats born to mothers treated with caffeine throughout pregnancy. Goes, AM; Ocarino, Nde M; Reis, AM; Ribeiro, LG; Serakides, R, 2015)	2.08
"Caffeine is a widely consumed psychoactive stimulant and is of epidemiologic interest. "	( Urine excretion of caffeine and select caffeine metabolites is common in the U.S. population and associated with caffeine intake. Ahluwalia, N; Pao, CI; Pfeiffer, CM; Rybak, ME; Sternberg, MR, 2015)	2.19
"Caffeine is an active adulterant found in several drugs of abuse including coca paste (CP). "	( Caffeine enhances and accelerates the expression of sensitization induced by coca paste indicating its relevance as a main adulterant. Abin-Carriquiry, JA; Galvalisi, M; López-Hill, X; Meikle, MN; Prieto, JP; Scorza, C, 2015)	3.3
"Caffeine is an increasingly popular nutritional supplement due to the legal, significant improvements in sporting performance that it has been documented to elicit, with minimal side effects. "	( What can isolated skeletal muscle experiments tell us about the effects of caffeine on exercise performance? Duncan, MJ; James, RS; Tallis, J, 2015)	2.09
"Caffeine is an alkaloid that can be toxic to insects and is hypothesized to act as a defence mechanism to inhibit herbivory."	( Gut microbiota mediate caffeine detoxification in the primary insect pest of coffee. Brodie, EL; Ceja-Navarro, JA; Hao, Z; Infante, F; Jenkins, S; Karaoz, U; Kosina, P; Lim, HC; Northen, TR; Vega, FE, 2015)	1.45
"Caffeine is a closely related xanthine derivative."	( Design and rationale of TROCADERO: A TRial Of Caffeine to Alleviate DyspnEa Related to ticagrelOr. Braun, OÖ; Christersson, C; Grove, EL; Halvorsen, S; James, SK; Lindholm, D; Storey, RF; Varenhorst, C, 2015)	1.4
"Caffeine is a widely used stimulant with potentially beneficial effects on cognition as well as vasoconstrictive properties. "	( Caffeine differentially alters cortical hemodynamic activity during working memory: a near infrared spectroscopy study. Heilbronner, U; Heinze, HJ; Hinrichs, H; Zaehle, T, 2015)	3.3
"Caffeine is a pharmacologically promising substance that deserves big consideration in the current research and development."	( The perspective of caffeine and caffeine derived compounds in therapy. Pohanka, M, 2015)	1.47
"Caffeine is a potent psychostimulant that can have significant and widely variable effects on the activity of multiple neuronal pathways. "	( Caffeine stimulates locomotor activity in the mammalian spinal cord via adenosine A1 receptor-dopamine D1 receptor interaction and PKA-dependent mechanisms. Acevedo, J; Cabezas-Bou, E; Díaz-Ríos, M; Marrero-Cordero, LR; Matos-Vergara, N; Santana-Almansa, A, 2016)	3.32
"Caffeine is an important naturally occurring compound which can be degraded by bacteria. "	( Application of response surface methodology for optimising caffeine-degrading parameters by Leifsonia sp. strain SIU. Abdul Khalil, K; Ahmad, SA; Halmi, MI; Ibrahim, S; Shukor, MY; Syed, MA, 2015)	2.1
"Caffeine, which is an ATM (ataxia telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3-related protein) kinase inhibitor, and KU55933, which is an ATM kinase inhibitor, were equally effective in rescuing the etoposide-induced cell-cycle blocks."	( Effect of ATM and HDAC Inhibition on Etoposide-Induced DNA Damage in Porcine Early Preimplantation Embryos. Cui, XS; Kim, NH; Kwon, J; Lee, IW; Lin, Z; Luo, Y; Wang, H, 2015)	1.14
"Caffeine is a natural alkaloid present in coffee, tea and soft drinks with well-known antibacterial properties."	( The coffee-machine bacteriome: biodiversity and colonisation of the wasted coffee tray leach. Iglesias, A; Porcar, M; Vilanova, C, 2015)	1.14
"Caffeine is an alkaloid that is widely consumed due to its presence in drugs, coffee, tea, and chocolate. "	( Inhibition of the osteogenic differentiation of mesenchymal stem cells derived from the offspring of rats treated with caffeine during pregnancy and lactation. Boeloni, JN; Ferreira, Ada F; Goes, AM; Gomes, DA; Ocarino, Nde M; Reis, AM; Serakides, R, 2016)	2.09
"Caffeine is a common component of everyday diet but also a popular ingredient of some analgesics. "	( THE INFLUENCE OF EXCIPIENTS ON PHYSICAL PROPERTIES OF TABLETS AND DISSOLUTION OF CAFFEINE. Belniak, P; Poleszak, E; Świader, K; Szumiło, M; Wojciechowska, J, )	1.8
"Caffeine is a white crystalline xanthine alkaloid found in the seeds of coffee plants and leaves of the tea bush. "	( Caffeine prevents LPS-induced inflammatory responses in RAW264.7 cells and zebrafish. Hwang, JH; Kim, KJ; Lee, BY; Ryu, SJ, 2016)	3.32
"Caffeine is a commonly used drug for apnea of prematurity. "	( Caffeine Prevents Hyperoxia-Induced Functional and Structural Lung Damage in Preterm Rabbits. Allegaert, K; Croubels, S; De Baere, S; Deprest, JA; Jiménez, J; Nagatomo, T; Naulaers, G; Richter, J; Toelen, J; Vanoirbeek, J, 2016)	3.32
"Caffeine is a commonly used psychoactive substance and consumption by children and adolescents continues to rise. "	( Adolescent caffeine consumption increases adulthood anxiety-related behavior and modifies neuroendocrine signaling. Archuleta, S; Bachtell, RK; Campeau, S; Levis, SC; Newsom, RJ; O'Neill, CE; Scott, T; Spencer, RL; Stafford, J, 2016)	2.27
"Caffeine is a non-selective antagonist at the adenosine receptors, which is expected to reverse both the intended (coronary vasodilation) and unintended (hypotension, flushing) effects of exogenously administered adenosine and adenosine-related compounds. "	( Caffeine reduces the sensitivity of vasodilator MPI for the detection of myocardial ischaemia: Pro. Reyes, E, 2016)	3.32
"Caffeine is a commonly used food additive found naturally in many products. "	( Caffeine inhibits TGFβ activation in epithelial cells, interrupts fibroblast responses to TGFβ, and reduces established fibrosis in ex vivo precision-cut lung slices. Barnes, J; Goodwin, A; Habgood, A; Jenkins, G; McAnulty, RJ; Tatler, AL, 2016)	3.32
"Caffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. "	( Caffeine and cardiovascular diseases: critical review of current research. Hayes, A; Klimas, J; Kobyliak, N; Kruzliak, P; Kubatka, P; La Rocca, G; Loftus, H; Novak, J; Pohanka, M; Qaradakhi, T; Smith, RM; Soucek, M; Uehara, Y; Zagatina, A; Zulli, A, 2016)	3.32
"Caffeine is a plant-derived psychostimulant and a common additive found in a wide range of foods and pharmaceuticals. "	( Quantitative Proteomic Analysis of the Orbital Frontal Cortex in Rats Following Extended Exposure to Caffeine Reveals Extensive Changes to Protein Expression: Implications for Neurological Disease. Cornish, JL; Franklin, JL; Goodchild, AK; Haynes, PA; Homewood, J; Mirzaei, M; Wearne, TA, 2016)	2.09
"Caffeine is an adenosine analog and acts as a nonselective adenosine receptor antagonist."	( Therapeutic Opportunities for Caffeine and A2A Receptor Antagonists in Retinal Diseases. Ambrósio, AF; Boia, R; Santiago, AR, 2016)	1.44
"Caffeine is a component with many applications and its penetration into the epidermis is controversially discussed in the literature."	( Confocal Raman microscopy and multivariate statistical analysis for determination of different penetration abilities of caffeine and propylene glycol applied simultaneously in a mixture on porcine skin ex vivo. Choe, C; Darvin, ME; Lademann, J; Maksimov, GV; Meinke, MC; Mujica Ascencio, S; Müller, RH; Wigger-Alberti, W, 2016)	1.36
"Caffeine is an adenosine receptor antagonist that may influence fertility by affecting ovulation, menstrual characteristics, or sperm quality. "	( Caffeine and caffeinated beverage consumption and fecundability in a preconception cohort. Hahn, KA; Hatch, EE; Mahalingaiah, S; Mikkelsen, EM; Rothman, KJ; Wesselink, AK; Wise, LA, 2016)	3.32
"Caffeine is a methylxanthine known as a non-specific inhibitor of adenosine (A2A and A1) receptors in the cerebrum and demonstrated to be a neuroprotective medication."	( Dose-dependent neuroprotective effect of caffeine on a rotenone-induced rat model of parkinsonism: A histological study. Fathalla, AM; Moustafa, AA; Soliman, AM, 2016)	1.42
"If caffeine consumption is a concern, it is important to inform consumers about the caffeine content of all caffeine containing beverages, including coffee and tea."	( Consumption of caffeinated beverages and the awareness of their caffeine content among Dutch students. Benson, S; Mackus, M; Scholey, A; van de Loo, AJAE; Verster, JC, 2016)	1.19
"Caffeine is an alkaloid which belongs to the family of methylxanthines and is present in beverages, food and drugs. "	( [Mechanisms of caffeine-induced diuresis]. Jouret, F; Marx, B; Scuvée, É; Scuvée-Moreau, J; Seutin, V, 2016)	2.23
"Caffeine, which is an antagonist of adenosine receptors, is the most widely consumed psychoactive drug in the world."	( Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma. Agudo-Barriuso, M; Ambrósio, AF; Madeira, MH; Nadal-Nícolas, F; Ortin-Martinez, A; Santiago, AR; Vidal-Sanz, M, 2016)	2.6
"Caffeine is a component of several beverages such as coffee and tea. "	( Effect of taurine and caffeine on plasma c-reactive protein and calcium in Wistar rats. Alashi, Y; Biliaminu, SA; Owoyele, BV; Oyewole, AL, 2015)	2.17
"Caffeine is a natural methylxanthine widespread throughout the food industry. "	( The influence of caffeine administered at 10°C on bone tissue development. Burdan, F; Dworzański, W; Olchowik, G; Tomaszewska, M; Tomaszewski, M, 2016)	2.22
"Caffeine is a psychostimulant commonly consumed with high levels of sugar. "	( Extended exposure to sugar and/or caffeine produces distinct behavioral and neurochemical profiles in the orbitofrontal cortex of rats: Implications for neural function. Cornish, JL; Franklin, JL; Goodchild, AK; Haynes, PA; Homewood, J; Mirzaei, M; Wearne, TA, 2016)	2.16
"Caffeine is a plant-derived alkaloid that is generally known as a central nervous system (CNS) stimulant. "	( Effects of Caffeine on Olfactory Learning in Crickets. Matsumoto, Y; Mizunami, M; Okada, J; Sugimachi, S, 2016)	2.27
"Caffeine is a widely consumed stimulant that has previously been shown to promote cytotoxic stress and even cell death in numerous mammalian cell lines. "	( Inhibiting c-Jun N-terminal kinase partially attenuates caffeine-dependent cell death without alleviating the caffeine-induced reduction in mitochondrial respiration in C2C12 skeletal myotubes. Baumgarner, BL; Downs, RM; Hughes, MA; Johnson, MC; Kinsey, ST, 2016)	2.12
"Caffeine is an adrenergic antagonist that enhances neuronal activity. "	( Protective effect of low dose caffeine on psychological stress and cognitive function. Akakın, D; Ellek, N; Hamamcı, R; Kasimay Cakir, O; Kayalı, DG; Keleş, H; Özbeyli, D; Salehin, N; Yüksel, M, 2017)	2.19
"Caffeine is a mild stimulant with significant potential for abuse, being consumed in larger doses with the widespread availability of energy drinks and by novel routes of administration such as inspired powder, oral sprays and electronic cigarettes. "	( Measurement of caffeine and its three primary metabolites in human plasma by HPLC-ESI-MS/MS and clinical application. Chen, F; Hu, ZY; Laizure, SC; Parker, RB, 2017)	2.25
"Caffeine is a methylxanthine that is widely used to treat apnea of prematurity (AOP). "	( Caffeine for apnea of prematurity: Effects on the developing brain. Atik, A; Cheong, J; De Matteo, R; Doyle, LW; Harding, R; Kondos-Devcic, D; Tolcos, M, 2017)	3.34
"Caffeine acts as an antagonist of A1 and A2A adenosine receptors and was shown to have a dose-dependent biphasic effect on locomotion in mice."	( Effects of caffeine on locomotor activity in streptozotocin-induced diabetic rats. Bădescu, SV; Georgescu, EL; Kobylinska, L; Tătaru, CP; Zăgrean, AM; Zăgrean, L; Zahiu, DM, )	1.24
"Caffeine is a competitive antagonist for adenosine receptors; however, it is unclear whether this antagonism affects FFR values."	( Effects of caffeine on fractional flow reserve values measured using intravenous adenosine triphosphate. Chikamori, T; Hijikata, N; Ito, R; Kimura, Y; Kobori, Y; Nakayama, M; Sato, H; Uchiyama, T; Yamashina, A; Yuhara, M, 2018)	1.59
"Caffeine is a widely consumed stimulant with the potential to enhance physical performance through multiple mechanisms. "	( The effect of caffeine on skeletal muscle anabolic signaling and hypertrophy. Adams, AJ; Ashby, CK; Bray, JK; Chen, T; Harris, AM; Kump, KJ; Laird, DW; Moore, TM; Mortensen, XM; Thomson, DM, 2017)	2.26
"Caffeine is a small amphiphilic molecule, which is widely consumed as a stimulant to prevent fatigue, but is also used as a common drug adjuvant in modern medicine. "	( Partitioning of caffeine in lipid bilayers reduces membrane fluidity and increases membrane thickness. Alsop, RJ; Backholm, M; Dhaliwal, A; Khondker, A; Rheinstädter, MC; Shi, AC; Tang, J, 2017)	2.24
"Caffeine is a promising drug for the management of neurodegenerative diseases such as Parkinson's disease (PD), demonstrating neuroprotective properties that have been attributed to its interaction with the basal ganglia adenosine A2A receptor (A2AR). "	( Synthesis and Characterization of a New Bivalent Ligand Combining Caffeine and Docosahexaenoic Acid. Azuaje, J; Ciruela, F; Cordobilla, B; Domingo, JC; Fernández-Dueñas, V; Morató, X; Sotelo, E, 2017)	2.13
"Caffeine is a well-known stimulant that can be used to increase alertness and performance especially in low arousal situations such as monotonous highway driving or after sleep deprivation. "	( Effects of caffeine on alertness as measured by infrared reflectance oculography. Johns, M; Michael, N; Owen, C; Patterson, J, 2008)	2.18
"Caffeine is an adenosine receptor antagonist that is commonly used in the clinic as a respiratory stimulant to treat apnea of prematurity. "	( Adenosinergic modulation of respiratory activity: developmental plasticity induced by perinatal caffeine administration. Bairam, A; Kinkead, R; Montandon, G, 2008)	2.01
"Caffeine is a widely used psychostimulant freely crossing the placental barrier. "	( Maternal caffeine ingestion during gestation and lactation influences respiratory adaptation to acute alveolar hypoxia in newborn rats and adenosine A2A and GABA A receptor mRNA transcription. Guénin, S; Larnicol, N; Perrin, Y; Picard, N, 2008)	2.21
"Caffeine is a common treatment for apnea of prematurity. "	( Enhancement of the breathing frequency response to hypoxia by neonatal caffeine treatment in adult male rats: the role of testosterone. Bairam, A; Joseph, V; Kinkead, R; Lajeunesse, Y; Montandon, G, 2009)	2.03
"Caffeine is a competitive antagonist at the adenosine receptors, but it is unclear whether caffeine in coffee alters the actions of exogenous adenosine, and whether the antagonism can be surmounted by increasing the adenosine dose."	( High-dose adenosine overcomes the attenuation of myocardial perfusion reserve caused by caffeine. Anagnostopoulos, C; Donovan, J; Harbinson, M; Loong, CY; Reyes, E; Underwood, SR, 2008)	2.01
"Caffeine is a well described and characterized ryanodine receptor (RyR) activator. "	( Caffeine inhibits InsP3 responses and capacitative calcium entry in canine pulmonary arterial smooth muscle cells. Hume, JR; McAllister, CE; Wilson, SM, )	3.02
"Caffeine is a proven ergogenic aid, increasing athletic performance, endurance, and mental chronometry at doses as low as 1-3 mg.kg-1. "	( Consumption of dietary caffeine and coffee in physically active populations: physiological interactions. Erdman, KA; Lun, V; Reimer, RA; Shearer, J; Tunnicliffe, JM, 2008)	2.1
"Caffeine is a commonly used neurostimulant that also produces cerebral vasoconstriction by antagonizing adenosine receptors. "	( The effect of daily caffeine use on cerebral blood flow: How much caffeine can we tolerate? Addicott, MA; Burdette, JH; Burnett, LR; Chen, MY; Hayasaka, S; Kraft, RA; Laurienti, PJ; Maldjian, JA; Peiffer, AM; Yang, LL, 2009)	2.12
"Caffeine acts as a stimulant, in which approximately 90% of people in the United States consume daily. "	( D-ribose--an additive with caffeine. Herrick, J; Shecterle, LM; St Cyr, JA, 2009)	2.09
"Caffeine is a popular psychostimulant, typically found in beverages. "	( Caffeine dose effect on activation-induced BOLD and CBF responses. Chen, Y; Parrish, TB, 2009)	3.24
"Caffeine is a widely used psychoactive substance in both adults and children that is legal, easy to obtain, and socially acceptable to consume. "	( Caffeine use in children: what we know, what we have left to learn, and why we should worry. Temple, JL, 2009)	3.24
"Caffeine is an opener to increase the calcium release channel open probability of sarcoplasmic reticulum (SR) in contraction phase."	( [Calcium leak of sarcoplasmic reticulum induces degradation of troponin I in skeletal muscle fibers.]. Jiao, B; Li, H; Li, Q; Wang, YY; Yu, ZB, 2009)	1.07
"Caffeine is a central nervous system stimulant that produces its primary effects via antagonism of the A(1) and A(2A) adenosine receptor subtypes. "	( Sex differences in caffeine neurotoxicity following chronic ethanol exposure and withdrawal. Berry, JN; Butler, TR; Prendergast, MA; Sharrett-Field, LJ; Smith, KJ, )	1.9
"Caffeine is a widely self-administered psychostimulant with purported neuroprotective and procognitive effects in rodent models of aging. "	( Caffeine elicits c-Fos expression in horizontal diagonal band cholinergic neurons. Fadel, JR; Pasumarthi, RK; Reznikov, LR, 2009)	3.24
"Caffeine is a natural alkaloid methylxanthine that is found in various plants such as coffee or tea. "	( A case of fatal caffeine poisoning. Knudsen, K; Rudolph, T, 2010)	2.15
"Caffeine is a commonly consumed drug during pregnancy with the potential to affect the developing fetus. "	( Caffeine intake during pregnancy, late miscarriage and stillbirth. Alwan, N; Boylan, S; Cade, JE; Charvill, J; Chipps, KC; Cooke, MS; Dolby, VA; Greenwood, DC; Hay, AW; Kassam, S; Kirk, SF; Konje, JC; Potdar, N; Shires, S; Simpson, N; Taub, N; Thomas, JD; Walker, J; White, KL; Wild, CP, 2010)	3.25
"Caffeine is a widely used and accepted pharmacologically active substance. "	( Maternal caffeine intake from coffee and tea, fetal growth, and the risks of adverse birth outcomes: the Generation R Study. Bakker, R; Hofman, A; Jaddoe, VW; Obradov, A; Raat, H; Steegers, EA, 2010)	2.22
"Caffeine is an antagonist at A1 and A2A adenosine receptors and epidemiological evidence suggests that caffeine consumption reduces the risk of Alzheimer's and Parkinson's diseases. "	( Caffeine attenuates lipopolysaccharide-induced neuroinflammation. Brothers, HM; Marchalant, Y; Wenk, GL, 2010)	3.25
"Caffeine is a psychostimulant with positive effects on cognition. "	( Caffeine prevents disruption of memory consolidation in the inhibitory avoidance and novel object recognition tasks by scopolamine in adult mice. Ardais, AP; Botton, PH; Costa, MS; da Rocha, JB; Mioranzza, S; Porciúncula, LO; Souza, DO, 2010)	3.25
"Caffeine is a methylxanthine alkaloid that can cause various supraventricular and ventricular arrhythmias."	( Caffeine-related atrial fibrillation. Arora, R; Artin, B; Jawad, E; Khosla, S; Richeh, C; Singh, M, )	2.3
"Caffeine is a neuroprotective drug known to inhibit the cell cycle, suggesting that its neuroprotective nature may rely, at least in part, on preventing tau abnormalities secondary to its inhibitory effect on neuronal cell cycle-related pathways."	( Caffeine modulates tau phosphorylation and affects Akt signaling in postmitotic neurons. Canuet, L; Currais, A; Ishii, R; Kato, K; Soriano, S; Takeda, M; Tanaka, T, 2011)	2.53
"Caffeine is a methylated-derivate of xanthine with profound effects on the onset and quality of sleep episodes."	( Purine molecules as hypnogenic factors role of adenosine, ATP, and caffeine. Díaz-Muñoz, M; Salín-Pascual, R, 2010)	1.32
"Caffeine is a silver bullet in neonatology. "	( Caffeine impact on neonatal morbidities. Aranda, JV; Beharry, K; Davis, J; Natarajan, G; Valencia, GB, 2010)	3.25
"Caffeine is a widespread known psychoactive substance that is present mainly in coffee, tea, soft and energy drinks. "	( [Coffee and caffeine - enemies or alliantes of a cardiologist?]. Anielska, E; Burdan, F; Dworzański, W; Jaskólska, A; Szumiło, M, 2011)	2.19
"Caffeine is a widely consumed psychoactive drug, which is emerging as a protective agent against AD progression and in aging associated deficits."	( Modulating Alzheimer's disease through caffeine: a putative link to epigenetics. Batalha, VL; Lopes, LV; Marques, S; Outeiro, TF, 2011)	1.36
"Caffeine is an antagonist at A(1) and A(2) adenosine receptors but it remains unclear whether anxiety is mediated by one or both of these."	( Adenosine A1, but not A2, receptor blockade increases anxiety and arousal in Zebrafish. Herculano, AM; Lima, MG; Maximino, C; Olivera, KR; Picanço-Diniz, DL, 2011)	1.09
"Caffeine is a psychostimulant with intake through foods or beverages tending to increase from childhood through adolescence. "	( Acute and adaptive motor responses to caffeine in adolescent and adult rats. Huggler, AL; Rhoads, DE; Rhoads, LJ, 2011)	2.08
"Caffeine is a mildly addictive psychoactive chemical and controversial additive to sugar-sweetened beverages (SSBs). "	( The influence of caffeine on energy content of sugar-sweetened beverages: 'the caffeine-calorie effect'. Keast, RS; Riddell, LJ; Sacks, G; Sayompark, D; Swinburn, BA, 2011)	2.15
"Caffeine is a "model" substance of dependence; coffee drinks are driving the recent increase in fast food sales."	( Is fast food addictive? Garber, AK; Lustig, RH, 2011)	1.09
"Caffeine, which is a widely consumed neural stimulant and vasoactive agent, has been found to decrease the amplitude and correlation of resting-state BOLD fluctuations, and hence is an important factor to consider in functional connectivity studies."	( Caffeine increases the temporal variability of resting-state BOLD connectivity in the motor cortex. Liu, TT; Rack-Gomer, AL, 2012)	2.54
"Caffeine is a source-specific indicator for wastewater, consumed and discharged in quantities allowing detection in a karst spring."	( Caffeine as an indicator for the quantification of untreated wastewater in karst systems. Geyer, T; Hillebrand, O; Licha, T; Nödler, K; Sauter, M, 2012)	2.54
"Caffeine use seemed to be an important factor for his atrial tachycardia, since his arrhythmia became worse during caffeine load testing and was ameliorated after the cessation of caffeine."	( A case of atrial tachycardia sensitive to increased caffeine intake. Kinugawa, T; Kurita, T; Nohara, R; Smith, ML, 2011)	1.34
"Caffeine is a widely consumed substance that occurs in numerous dietary sources, but teratogenic effects of caffeine intake during embryonic development are still not clear. "	( Caffeine treatment disturbs the angiogenesis of zebrafish embryos. Chang, CY; Chen, YH; Cheng, CC; Liao, YF; Tsai, JN; Wang, YH; Wen, CC; Yeh, CH, 2012)	3.26
"Caffeine is a widely used substance with effects on several systems, presenting characteristic of pharmacokinetic and pharmacodynamic which cause interactions with several drugs. "	( Caffeine in the treatment of pain. Sakata, RK; Tavares, C, )	3.02
"Caffeine use is a public health issue and its risks and benefits are regularly considered in scientific literature and the lay media."	( Caffeine use among active duty US Army soldiers. Hadden, L; Lieberman, HR; Marriott, BP; McGraw, S; Stavinoha, T; White, A, 2012)	2.54
"Caffeine is a constituent of many non-alcoholic beverages. "	( Caffeine attenuates metabolic syndrome in diet-induced obese rats. Brown, L; Kauter, K; Panchal, SK; Ward, LC; Wong, WY, 2012)	3.26
"Caffeine is a non-selective adenosine antagonist commonly used to facilitate effortful tasks, and thus may affect decisions involving effort costs in humans."	( Caffeine increases psychomotor performance on the effort expenditure for rewards task. de Wit, H; Treadway, MT; Wardle, MC, 2012)	2.54
"Caffeine is a globally consumed psychostimulant but can be fatal to cells at overdose exposures. "	( Arachidonic acid enhances caffeine-induced cell death via caspase-independent cell death. Kuwayama, H, 2012)	2.12
"Caffeine is a stimulant of central nervous system and therefore is probably the most commonly used psychoactive substance in the world."	( [Caffeine--common ingredient in a diet and its influence on human health]. Wierzejska, R, 2012)	2.01
"Caffeine is a definite factor of intrauterine growth retardation (IUGR). "	( A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion. Chen, LB; Lei, YY; Liu, F; Liu, J; Liu, YS; Magdalou, J; Ping, J; Qin, J; Shen, L; Wang, H; Wu, Y; Xu, D; Zhang, C, 2012)	2.02
"Caffeine is a methylxanthine which permeates the placenta. "	( Use of X-ray microprobe to diagnose bone tissue demineralization after caffeine administration. Burdan, F; Olchowik, G; Tomaszewska, M; Tomaszewski, M, 2012)	2.05
"Caffeine is a methylxanthine alkaloid with a reported canine oral median lethal dose (MLD(50)) of 140 mg/kg (range 120-200 mg/kg)."	( Death by caffeine: presumptive malicious poisoning of a dog by incorporation in ground meat. Albin, T; Poppenga, RH; Puschner, B; Stump, S; Tawde, SN, 2012)	1.52
"Caffeine is a nonselective adenosine receptor antagonist; chronic consumption has proved protective toward neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. "	( Effects of chronic caffeine intake in a mouse model of amyotrophic lateral sclerosis. Armida, M; Ferrante, A; Matteucci, A; Pèzzola, A; Popoli, P; Potenza, RL; Puopolo, M, 2013)	2.16
"Caffeine dependence is a frequent cause of chronic daily headache. "	( [Chronic daily headaches caused by too much caffeine]. Schonewille, WJ, 2002)	2.02
"Caffeine is an analgesic adjuvant, but also has panicogenic properties. "	( The moderating effect of anxiety sensitivity on caffeine-induced hypoalgesia in healthy women. Chaloner, N; Keogh, E, 2002)	2.01
"Caffeine is an efficient inhibitor of cellular DNA repair, likely through its effects on ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) kinases. "	( Evidence that the retroviral DNA integration process triggers an ATR-dependent DNA damage response. Daniel, R; Favorova, O; Greger, JG; Kao, G; Katz, RA; Merkel, G; Skalka, AM; Taganov, K; Yen, TJ, 2003)	1.76
"Caffeine is a key component of many popular drinks, especially tea and coffee. "	( Induction of apoptosis by caffeine is mediated by the p53, Bax, and caspase 3 pathways. Bode, AM; Dong, Z; Hashimoto, T; He, Z; Ma, WY; Yang, CS, 2003)	2.06
"Caffeine is a receptor antagonist for adenosine that might interfere with the neuroprotective effect of adenosine in ischemic-hypoxic conditions."	( Caffeine impairs short-term neurological outcome after concussive head injury in rats. Ahmad Khan, H; Al Deeb, S; Al Moutaery, K; Tariq, M, 2003)	2.48
"Caffeine is a factor, as regular ingestion of caffeine has been shown to potentially lead to a physical desire to habitually ingest caffeine."	( Adolescent caries: a discussion on diet and other factors, including soft drink consumption. Majewski, RF, 2001)	1.03
"Caffeine is a marker drug for testing the activity of CYP1A2 (3-N-demethylation) in humans and rats. "	( Influence of classic and atypical neuroleptics on caffeine oxidation in rat liver microsomes. Daniel, WA; Kot, M; Wójcikowski, J, )	1.83
"Caffeine acts as an antagonist to both types of receptors."	( Caffeine as a psychomotor stimulant: mechanism of action. Borgkvist, A; Fisone, G; Usiello, A, 2004)	2.49
"Caffeine is a major biologically active constituent in coffee and tea. "	( Caffeine inhibits cell proliferation by G0/G1 phase arrest in JB6 cells. Bode, AM; Dong, Z; Hashimoto, T; He, Z; Ma, WY; Schmid, PC; Yang, CS, 2004)	3.21
"IV caffeine appears to be an effective treatment for PH in children with sedation-induced PH. "	( Oral and intravenous caffeine for treatment of children with post-sedation paradoxical hyperactivity. Bartko, M; Baskin, KM; Cahill, AM; Kaye, RD; Rubin, JT; Towbin, RB, 2004)	1.26
"Caffeine is a compound with documented ergogenicity in various exercise modalities, while ephedrine and related alkaloids have not been shown, as yet, to result in any significant performance improvements."	( Caffeine and ephedrine: physiological, metabolic and performance-enhancing effects. Kavouras, SA; Magkos, F, 2004)	2.49
"As caffeine is a non-selective adenosine receptor antagonist the ability of adenosine A(1) and A(2A) receptor blockade to attenuate ethanol-induced motor incoordination was determined."	( Adenosine A1 receptor blockade mimics caffeine's attenuation of ethanol-induced motor incoordination. Connole, L; Harkin, A; Maginn, M, 2004)	1.11
"Caffeine is an efficient inhibitor of DNA repair and DNA damage-activated checkpoints. "	( Caffeine inhibits human immunodeficiency virus type 1 transduction of nondividing cells. Argyris, E; Daniel, R; Marusich, E; Pomerantz, RJ; Skalka, AM; Zhao, RY, 2005)	3.21
"Caffeine is a non-selective adenosine receptor antagonist in vitro, but involvement of different adenosine receptor subtypes, particularly adenosine A1 and A 2A receptors, in the central effects of caffeine remains a matter of debate."	( Involvement of adenosine A1 receptors in the discriminative-stimulus effects of caffeine in rats. Antoniou, K; Ferré, S; Goldberg, SR; Hockemeyer, J; Justinova, Z; Müller, CE; Pappas, LA; Quarta, D; Segal, PN; Solinas, M; Wertheim, C, 2005)	2
"Caffeine is a widely used psychoactive substance that has the potential to contribute to many psychiatric symptoms. "	( Caffeine and psychiatric symptoms: a review. Benjamin, AB; Broderick, P, 2004)	3.21
"Caffeine is a mild central nervous stimulant that occurs naturally in coffee beans, cocoa beans and tea leaves. "	( Fatal caffeine overdose: two case reports. Kerrigan, S; Lindsey, T, 2005)	2.25
"Caffeine is a constituent of a variety of beverages (coffee, tea and caffeinated soft drinks) and of numerous food products (chocolate, pastries and dairy desserts)."	( Anthropic pollution in aquatic environment: development of a caffeine indicator. da Cunha, Cde L; Ferreira, AP, 2005)	1.29
"Caffeine is a methylxanthine that inhibits phosphodiesterase enzyme and results in a higher concentration of intracellular cAMP."	( Evaluation of the efficacy of topical caffeine in the treatment of psoriasis vulgaris. Asilian, A; Khalesi, E; Khoddami, L; Mohammady, M; Shahtalebi, M; Vali, A, 2005)	1.32
"Caffeine is a very common CNS stimulant that has been of interest to physiologists because of its direct effects on skeletal muscle in vitro, as well as ergogenic effects on laboratory tests of human performance. "	( The influence of caffeine on voluntary muscle activation. Kalmar, JM, 2005)	2.11
"Caffeine is an ingredient in a variety of beverages (coffee, tea, and caffeinated soft drinks) and numerous food products (chocolate, pastries, and dairy desserts)."	( Caffeine as an environmental indicator for assessing urban aquatic ecosystems. Ferreira, AP, )	2.3
"Caffeine is a widely consumed stimulant, although its cardiovascular safety remains controversial and its effect on MBF is unknown."	( Caffeine decreases exercise-induced myocardial flow reserve. Delaloye, R; Fleischmann, SP; Gaemperli, O; Grathwohl, R; Kaufmann, PA; Klainguti, M; Koepfli, P; Namdar, M; Schepis, T; Siegrist, PT; Wyss, CA, 2006)	3.22
"Caffeine is a mixed adenosine receptor antagonist, therefore its effects could be due to a different action on adenosine receptor subtypes; an additional mechanism of action cannot be excluded."	( Biphasic effect of chronic postnatal caffeine treatment on cortical epileptic afterdischarges during ontogeny in rats. Kubová, H; Mares, P; Tchekalarova, J, 2006)	1.33
"Caffeine is a member of the methylxanthine family of drugs, and is the most widely consumed behaviourally active substance in the western world. "	( Immunomodulatory effects of caffeine: friend or foe? Connor, TJ; Horrigan, LA; Kelly, JP, 2006)	2.07
"Caffeine was found to be a suppressor of fat absorption, while chlorogenic acid was found to be partially involved in the suppressive effect of GCBE that resulted in the reduction of hepatic TG level."	( Inhibitory effect of green coffee bean extract on fat accumulation and body weight gain in mice. Aitani, M; Seki, E; Shimoda, H, 2006)	1.06
"Caffeine is an adenosine receptor antagonist commonly used as a respiratory stimulant to treat neonatal apneas of premature newborn. "	( Long-term consequences of neonatal caffeine on ventilation, occurrence of apneas, and hypercapnic chemoreflex in male and female rats. Bairam, A; Kinkead, R; Montandon, G, 2006)	2.05
"Caffeine is a naturally occurring substance that is widely consumed in a variety of forms. "	( Caffeine as an ergogenic aid. Armsey, TD; Keisler, BD, 2006)	3.22
"Caffeine is a ubiquitous compound in raw, domestic wastewater with typical per capita loads of approximately 16 mg person(-1) d(-1)."	( Combined sewer overflows to surface waters detected by the anthropogenic marker caffeine. Buerge, IJ; Buser, HR; Müller, MD; Poiger, T, 2006)	1.28
"Caffeine is a natural purine analogue that elicits pleiotropic effects leading ultimately to cell's death by a largely uncharacterized mechanism. "	( Investigating the caffeine effects in the yeast Saccharomyces cerevisiae brings new insights into the connection between TOR, PKC and Ras/cAMP signalling pathways. François, J; Kuranda, K; Leberre, V; Palamarczyk, G; Sokol, S, 2006)	2.11
"Caffeine is a methylxanthine present in the coffee tree, tea plant, and other naturally occurring sources and is among the most commonly consumed drugs worldwide. "	( A taste receptor required for the caffeine response in vivo. Jiao, Y; Köttgen, M; Montell, C; Moon, SJ; Xu, H, 2006)	2.06
"Caffeine is a safe and effective strategy to enhance cognitive performance and is an ingredient in some tube foods."	( Caffeinated tube food effect on pilot performance during a 9-hour, simulated nighttime U-2 mission. Doan, BK; Fischer, JR; Hickey, PA; Lieberman, HR, 2006)	1.06
"Caffeine is a commonly used probe to assess the metabolic activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO)."	( Differential alteration of drug-metabolizing enzyme activities after cyclophosphamide/adriamycin administration in breast cancer patients. Altundag, K; Babaoglu, MO; Bozkurt, A; Dincel, AK; Elkiran, T; Guler, N; Harputluoglu, H; Ozisik, Y; Yasar, U, )	0.85
"Caffeine is a nonselective competitive blockade of adenosine A1 and A2A receptors. "	( Effects of caffeine on the freezing of gait in Parkinson's disease. Houzen, H; Kitagawa, M; Tashiro, K, 2007)	2.17
"Caffeine acts as a non-selective adenosine receptor antagonist in the central nervous system."	( [Caffeine: a nutrient, a drug or a drug of abuse]. Alvarez García, Y; Barral Tafalla, D; Farré Albaladejo, M; Pardo Lozano, R, 2007)	1.97
"Caffeine is a well-known stimulant that is added as an ingredient to various carbonated soft drinks. "	( Caffeine content of prepackaged national-brand and private-label carbonated beverages. Bell, LN; Chou, KH, 2007)	3.23
"Caffeine is a nonselective adenosine receptor antagonist that blocks 2 major types of adenosine receptors, A1AR and A2AAR, in the brain."	( Adenosine and dopamine receptor interactions in striatum and caffeine-induced behavioral activation. Ramkumar, V; Toth, LA; Xie, X, 2007)	1.3
"Caffeine is a non-specific antagonist of adenosine receptors and can reach the immature brain."	( Maternal caffeine intake affects acetylcholinesterase in hippocampus of neonate rats. Battastini, AM; Bogo, MR; Bonan, CD; da Silva, RS; da Silveira, VG; Lara, DR; Richetti, SK, )	1.27
"Caffeine is a nonspecific adenosine receptor blocker, and thus drinking CC may block the myocardial protective effects of statins."	( Caffeinated coffee blunts the myocardial protective effects of statins against ischemia-reperfusion injury in the rat. Abu Said, GH; Birnbaum, Y; Hughes, MG; Lin, Y; Manickavasagam, S; McAdoo, DJ; Perez-Polo, RJ; Ye, Y, 2008)	1.07
"Caffeine is a methylxanthine compound that acts as a stimulant in humans. "	( In vitro prooxidant effect of caffeine. Gülçin, I, 2008)	2.08
"Caffeine is a popular stimulant often used to counter the effects of sleep loss and fatigue. "	( Effects of acute caffeine withdrawal on Short Category Test performance in sleep-deprived individuals. Balkin, TJ; Kahn-Greene, ET; Kamimori, GH; Killgore, DB; Killgore, WD, 2007)	2.12
"Caffeine is known to be a cardiac stimulant and is one of the drugs most widely used by the American population."	( Epinephrine-induced cardiac arrhythmias in rabbits exposed to trichloroethylene: potentiation by caffeine. Carlson, GP; White, JF, )	1.07
"Caffeine is a central nervous system stimulant that has come under increasing scrutiny due to its effects on the health and mental health of those who consume it. "	( Caffeine: implications of recent research for clinical practice. Wells, SJ, 1984)	3.15
"Caffeine is a drug which easily crosses the placental barrier and enters the fetal circulation. "	( Caffeine and pregnancy outcome. Weigle, A; Worthington-Roberts, B, )	3.02
"Caffeine is a commonly used drug that is metabolized predominantly by a component of the hepatic microsomal mixed-function oxidase complex, known as cytochrome P-448."	( Inhibition of caffeine elimination by short-term ethanol administration. Hoyumpa, AM; Johnson, RF; Mitchell, MC; Nichols, S; Patwardhan, RV; Schenker, S, 1983)	1.35
"Caffeine acts as a comutagen for the induction by EMS of mutant phages and produces a significant increase in the frequency of reversions from rII to r+."	( Caffeine as a comutagen for ethylmethanesulfonate in strains of phage T4. Lockhart, ML; Shankel, DM, 1980)	2.43
"Caffeine is found to be a more efficient releaser of cellular Ca than noradrenaline."	( General features of electrical and mechanical properties of smooth muscle cells in the guinea-pig abdominal aorta. Kajiwara, M, 1982)	0.99
"Caffeine is a widely used drug with various biological effects. "	( Caffeine influence on the motor steadiness battery in neuropsychological tests. Bovim, G; Helle, J; Naess, P; Sand, T, 1995)	3.18
"Caffeine is a commonly used drug that increases arousal, a condition associated with increased cholinergic activity in the mammalian cerebral cortex including the hippocampus. "	( Caffeine enhances acetylcholine release in the hippocampus in vivo by a selective interaction with adenosine A1 receptors. Carter, AJ; Carter, MJ; O'Connor, WT; Ungerstedt, U, 1995)	3.18
"Caffeine is a methylxanthine whose primary biological effect is the competitive antagonism of the adenosine receptor. "	( Caffeine and coffee: effects on health and cardiovascular disease. Benowitz, NL; Chou, TM, 1994)	3.17
"Caffeine is a commonly consumed methylxanthine that provides a model for evaluating the impact of this category of drugs on radiation injury."	( Caffeine consumption is associated with decreased severe late toxicity after radiation to the pelvis. Greer, BE; Griffin, TW; Koh, WJ; Kurtz, H; Stelzer, KJ, 1994)	2.45
"Caffeine is a popular compound for phenotyping individuals for CYP4501A2, xanthine oxidase (XO) and N-acetyltransferase (NAT) utilising urinary metabolites. "	( Rapid method for the routine determination of caffeine and its metabolites by high-performance liquid chromatography. Bennett, PN; Dobrocky, P; Notarianni, LJ, 1994)	1.99
"Caffeine is a base analogue and is known to affect a wide variety of cellular processes. "	( Caffeine-resistance in fission yeast is caused by mutations in a single essential gene, crm1+. Kumada, K; Toda, T; Yanagida, M, 1996)	3.18
"Caffeine is a potentially useful alternative to theophylline for the treatment and prevention of apnea of prematurity because of its lower toxicity and longer terminal half-life. "	( Saliva as a valid alternative to serum in monitoring intravenous caffeine treatment for apnea of prematurity. Charles, BG; Flenady, VJ; Lee, TC; Steer, PA, 1996)	1.97
"Caffeine is a well known base analogue and is cytotoxic to both animal and yeast cells. "	( Caffeine-resistance in S. pombe: mutations in three novel caf genes increase caffeine tolerance and affect radiation sensitivity, fertility, and cell cycle. Benko, Z; Carr, AM; Miklos, I; Sipiczki, M, 1997)	3.18
"Caffeine is a competitive antagonist at adenosine receptors and produces a range of central and physiological effects that are opposite those of adenosine."	( The role of dopamine in the behavioral effects of caffeine in animals and humans. Garrett, BE; Griffiths, RR, 1997)	1.27
"Caffeine is a widely consumed substance that elicits psychomotor stimulant effects and also displays addictive properties. "	( Concurrent elevation of the levels of expression of striatal preproenkephalin and preprodynorphin mRNA in the rat brain by chronic treatment with caffeine. Angulo, JA; Datta, U; Kraft, M; Noailles, PA; Zhang, Y, 1997)	1.94
"Caffeine is an addictive psychoactive substance. "	( Caffeine intake, tolerance, and withdrawal in women: a population-based twin study. Kendler, KS; Prescott, CA, 1999)	3.19
"Caffeine is a metabolic probe for the quantitative measurement of CYP1A2 activity in vivo."	( Effect of venlafaxine on CYP1A2-dependent pharmacokinetics and metabolism of caffeine. Albano, D; Amchin, J; Klockowski, PM; Taylor, KP; Zarycranski, W, 1999)	1.25
"Caffeine is a substance which many people consume in their daily life. "	( Effects of caffeine on the bones of aged, ovariectomized rats. Cheuk, G; Falster, AU; Kamagata-Kiyoura, Y; Nakamoto, T; Ohta, M; Simmons, WB; Thomas, KA; Wink, CS; Yazdani, M, 1999)	2.14
"Caffeine is considered to be a dehydrating agent with detrimental effects on the quality of voice of persons ingesting it. "	( Effect of caffeine on the vocal folds: a pilot study. Akhtar, S; O'Flynn, PE; Ratcliffe, P; Rubin, JS; Wood, G, 1999)	2.15
"Caffeine is a non-selective A(1)/A(2 )adenosine receptor antagonist which is known to improve cognitive performance in humans. "	( Adenosine and memory storage: effect of A(1) and A(2) receptor antagonists. Kopf, SR; Melani, A; Pedata, F; Pepeu, G, 1999)	1.75
"Caffeine is a behavioral stimulant consumed on a worldwide basis. "	( Dose-response study of caffeine effects on cerebral functional activity with a specific focus on dependence. Boyet, S; Nehlig, A, 2000)	2.06
"Caffeine is a weak bronchodilator and it also reduces respiratory muscle fatigue. "	( Caffeine for asthma. Bara, AI; Barley, EA, 2000)	3.19
"Caffeine is an effective analgesic adjuvant because it increases the antinociceptive effect of NSAIDs while reducing the probability of side effects. "	( A review of the pharmacokinetic and pharmacodynamic factors in the potentiation of the antinociceptive effect of nonsteroidal anti-inflammatory drugs by caffeine. Castañeda-Hernández, G; Granados-Soto, V, 1999)	1.94
"Caffeine is an added ingredient in approximately 70% of soft drinks consumed in the United States."	( Is caffeine a flavoring agent in cola soft drinks? Griffiths, RR; Vernotica, EM, 2000)	1.65
"Caffeine is an alkaloid widely consumed by humans."	( Caffeine decreases the occurrence of cadmium-induced forelimb ectrodactyly in C57BL/6J mice. Beck, SL; Lutz, J, 2000)	2.47
"Caffeine is a common psychoactive constituent of coffee, carbonated beverages, and over-the-counter medications. "	( Changes in the ambulatory activity and discriminative stimulus effects of psychostimulant drugs in rats chronically exposed to caffeine: effect of caffeine dose. Gasior, M; Goldberg, SR; Jaszyna, M; Peters, J, 2000)	1.96
"Caffeine is a widespread natural methylaxanthine which easily crosses the placenta. "	( [Teratogenic and embryotoxic effects of caffeine: facts and hypotheses]. Burdan, F, 2000)	2.02
"Caffeine is an environmental agent to which people are commonly exposed through medicines, drinks, food items, etc. "	( Effect of caffeine on the genotoxic effects of gamma radiation and 4-NQO in diploid yeast. Anjaria, KB; Rao, BS, 2001)	2.16
"Caffeine is an excellent model compound for understanding drugs of abuse/dependence. "	( Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement. Chausmer, AL; Griffiths, RR, 2000)	3.19
"Caffeine is a methylated xanthine that acts as a mild central nervous system stimulant. "	( Teratogen update: evaluation of the reproductive and developmental risks of caffeine. Brent, RL; Christian, MS, 2001)	1.98
"Caffeine is a common substance in the diets of most athletes and it is now appearing in many new products, including energy drinks, sport gels, alcoholic beverages and diet aids. "	( Caffeine and exercise: metabolism, endurance and performance. Graham, TE, 2001)	3.2
"Caffeine is a weak bronchodilator and it also reduces respiratory muscle fatigue. "	( Caffeine for asthma. Bara, AI; Barley, EA, 2001)	3.2
"Caffeine is a cerebral vasoconstrictor that causes an increase in the concentration of deoxyhemoglobin and thus a decrease in the BOLD baseline resting signal by 4.4%."	( On the use of caffeine as a contrast booster for BOLD fMRI studies. Gitelman, DR; Mesulam, MM; Mulderink, TA; Parrish, TB, 2002)	1.4
"Caffeine is an adenosine A(2A) receptor antagonist that enhances locomotor activity in animal models of parkinsonism."	( Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson's disease. Petrovitch, H; Ross, GW, 2001)	1.27
"Caffeine is a central stimulant that increases the release of catecholamines. "	( Caffeine can decrease insulin sensitivity in humans. De Galan, BE; Keijzers, GB; Smits, P; Tack, CJ, 2002)	3.2
"Caffeine consumption is an important issue, and a consistent measurement system should be used by various researchers testing different populations."	( Caffeine consumption questionnaire: a standardized measure for caffeine consumption in undergraduate students. Landrum, RE; Shohet, KL, 2001)	2.47
"Caffeine is a model radiosensitizing agent that is thought to work by abrogating the radiation-induced G(2)-phase checkpoint. "	( Caffeine induces TP53-independent G(1)-phase arrest and apoptosis in human lung tumor cells in a dose-dependent manner. Martinez, JD; Qi, W; Qiao, D, 2002)	3.2
"Caffeine reduction is an internationally accepted treatment strategy for patients with urinary symptoms. "	( Caffeine reduction education to improve urinary symptoms. Bryant, CM; Dowell, CJ; Fairbrother, G, )	3.02
"Caffeine is a marker drug for testing the activity of CYP1A2 (3-N-demethylation) in humans and rats. "	( Effects of antidepressant drugs on the activity of cytochrome P-450 measured by caffeine oxidation in rat liver microsomes. Danie, WA; Ryłko, Z; Syrek, M; Wójcikowski, J, )	1.8
"Caffeine is a popular test substance for assessing the activity of hepatic drug metabolizing enzymes in vivo and in vitro. "	( Intra-individual variability of caffeine elimination in healthy subjects. Balogh, A; Harder, S; Staib, AH; Vollandt, R, 1992)	2.01
"Caffeine is a methylxanthine whose primary biologic effect is antagonism of the adenosine receptor. "	( Wake up and smell the coffee. Caffeine, coffee, and the medical consequences. Chou, T, 1992)	2.01
"Caffeine is a competitive antagonist at adenosine receptors. "	( Role of adenosine receptors in caffeine tolerance. Holtzman, SG; Mante, S; Minneman, KP, 1991)	2.01
"Caffeine is a methylxanthine, commonly used in the premature neonate to treat apnea of prematurity. "	( Neonatal exposure to therapeutic caffeine alters the ontogeny of adenosine A1 receptors in brain of rats. Guillet, R; Kellogg, C, 1991)	2.01
"Caffeine was shown to be a novel inhibitor of NAD(P)H dehydrogenase (quinone) and also elicited the above protective effects."	( Caffeine, aminoimidazolecarboxamide and dicoumarol, inhibitors of NAD(P)H dehydrogenase (quinone) (DT diaphorase), prevent both the cytotoxicity and DNA interstrand crosslinking produced by 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) in Walker cells. Boland, MP; Friedlos, F; Knox, RJ; Kotsaki-Kovatsi, VP; Marchbank, T; Roberts, JJ, 1989)	2.44
"Caffeine is a widely ingested and generally beneficial drug. "	( Caffeine and caffeinism. Mackay, DC; Rollins, JW, 1989)	3.16
"Caffeine is a teratogen that causes limb and palate malformations in rodents. "	( Caffeine effects on cyclic AMP levels in the mouse embryonic limb and palate in vitro. Schreiner, CM; Scott, WJ; Wee, EL; Zimmerman, EF, 1986)	3.16
"Caffeine at high doses is a known rodent teratogen and induces limb malformations along with cleft palate in various strains of rats and mice. "	( Prevention of caffeine-induced limb malformations by maternal adrenalectomy. Moriguchi, M; Scott, WJ, 1986)	2.07

Effects

Caffeine consumption has an association with alcohol use and smoking habit among males. Caffeine is a widely used medication for prevention and treatment of apnoea of prematurity.

Caffeine has been shown to have effects on certain areas of cognition, but in executive functioning the research is limited and also inconsistent. Caffeine consumption has a well-known diuretic effect. It can potentially be useful as a body weight regulator.

Excerpt	Reference	Relevance
"Caffeine has an anti-infectious potential and ameliorated infection-derived inflammation following experimental infection with L. "	( Anti-inflammatory activity of caffeine (1,3,7-trimethylxanthine) after experimental challenge with virulent Listeria monocytogenes in Swiss mice. de Alcântara Almeida, I; Mancebo Dorvigny, B; Nunes Santana, L; Souza Tavares, L; Vitor Lima-Filho, J, 2021)	2.35
"Caffeine has a significant effect on cerebrovascular systems, and the dual action of caffeine on both neural and vascular responses leads to concerns for the interpretation of blood oxygenation level-dependent (BOLD) functional MRI. "	( Cerebral hemodynamic response to caffeine: effect of dietary caffeine consumption. Chu, LWL; Peng, SL; Su, FY, 2022)	2.45
"Caffeine has a wide range of effects in humans and other organisms. "	( Caffeine activates HOG-signalling and inhibits pseudohyphal growth in Saccharomyces cerevisiae. Blomberg, A; Elhasi, T, 2023)	3.8
"Caffeine has an anti-obesity effect, although chronic excessive caffeine consumption also causes caffeinism, which is marked by increased anxiety or depression, amongst other symptoms. "	( Astilbin lowers the effective caffeine dose for decreasing lipid accumulation via activating AMPK in high-fat diet-induced obese mice. Yang, L; Zheng, G; Zhong, S; Zhu, Y, 2021)	2.35
"Caffeine has a well-established effect on reaction times (RTs) but the neurocognitive mechanisms underlying this are unclear."	( Effects of caffeine on reaction time are mediated by attentional rather than motor processes. de Morree, HM; Dundon, NM; Klein, C; Marcora, SM; Saville, CWN, 2018)	2.31
"Caffeine has a small but evident effect on endurance performance when taken in moderate doses (3-6 mg/kg) as well as an overall improvement following caffeine compared to placebo in mean power output (3.03 ± 3.07%; effect size = 0.23 ± 0.15) and time-trial completion time (2.22 ± 2.59%; effect size = 0.41 ± 0.2)."	( The Effect of Acute Caffeine Ingestion on Endurance Performance: A Systematic Review and Meta-Analysis. Ali, A; Rutherfurd-Markwick, KJ; Southward, K, 2018)	1.53
"Caffeine has a very favorable benefit-to-risk ratio, and has become one of the most prescribed and cost-effective pharmacotherapies in the NICU."	( Caffeine: an evidence-based success story in VLBW pharmacotherapy. Dobson, NR; Hunt, CE, 2018)	2.64
"Caffeine has a strong antagonistic effect against theanine."	( Stress-Reducing Function of Matcha Green Tea in Animal Experiments and Clinical Trials. Furushima, D; Hamamoto, S; Horie, H; Iguchi, K; Morita, A; Nakamura, Y; Unno, K; Yamada, H, 2018)	1.2
"Caffeine has a well-established effect on intraocular pressure (IOP) and ocular perfusion pressure (OPP); however, the possible differences between low- and high-caffeine consumers remain unknown."	( Effects of caffeine on intraocular pressure are subject to tolerance: a comparative study between low and high caffeine consumers. Bermúdez, J; Jiménez, R; Molina, R; Redondo, B; Vera, J, 2019)	2.35
"Caffeine also has an effect on the central nervous system (CNS), and it is now recognized that most of the performance-enhancing effect of caffeine is accomplished through the antagonism of the adenosine receptors, influencing the dopaminergic and other neurotransmitter systems."	( Caffeine, exercise and the brain. Meeusen, R; Roelands, B; Spriet, LL, 2013)	2.55
"Caffeine has a preventive effect on ALF."	( Caffeine protects against alcohol-induced liver fibrosis by dampening the cAMP/PKA/CREB pathway in rat hepatic stellate cells. Dai, X; Li, J; Lv, X; Wang, H; Wang, Q; Yang, F; Yang, W; Yang, Y; Zhao, H, 2015)	2.58
"Caffeine consumption has a well-known diuretic effect."	( [Mechanisms of caffeine-induced diuresis]. Jouret, F; Marx, B; Scuvée, É; Scuvée-Moreau, J; Seutin, V, 2016)	1.51
"Caffeine has a variety of pharmacological effects; it is a weak bronchodilator and it also reduces respiratory muscle fatigue. "	( Caffeine for asthma. Bara, A; Barley, E; Cates, CJ; Welsh, EJ, 2010)	3.25
"Caffeine has a potential role in promoting alertness during times of desired wakefulness in persons with jet lag or shift work disorder, however its effects on injury and error are unclear."	( Caffeine for the prevention of injuries and errors in shift workers. Blackhall, K; Edwards, PJ; Felix, LM; Ker, K; Roberts, I, 2010)	2.52
"Caffeine also has a potentially negative influence on bones."	( The influence of caffeine on the biomechanical properties of bone tissue during pregnancy in a population of rats. Chadaj-Polberg, E; Olchowik, G; Polberg, M; Tomaszewska, M; Tomaszewski, M, 2011)	1.43
"Caffeine, which has a DNA-repair inhibiting effect, enhances the cytocidal effects of anticancer drugs and radiation. "	( Caffeine-potentiated chemotherapy for patients with high-grade soft tissue sarcoma: long-term clinical outcome. Hayashi, K; Kawahara, M; Miyamoto, K; Takeuchi, A; Tomita, K; Tsuchiya, H; Yamamoto, N; Yamauchi, K, )	3.02
"Caffeine has a variety of pharmacological effects but its affinity for adenosine receptors is comparable with the levels expected to exist in the body after moderate caffeine intake, thus making adenosine receptor blockade the favoured mode of ergogenic action."	( Caffeine and other sympathomimetic stimulants: modes of action and effects on sports performance. Jones, G, 2008)	2.51
"Caffeine has a multitude of pharmacologic actions and its effects must be determined on the fetus and newborn in the immediate future for suggestive evidence links caffeine with such fetal and newborn pathology as pre- and postmaturity and intrauterine growth retardation."	( Caffeine ingestion during pregnancy: in utero exposure and possible effects. Soyka, LF, 1981)	2.43
"Caffeine has a biphasic effect on Ca(2+)-activated K+ current [IK(Ca)]: it induces a transient increase superimposed upon a sustained inhibition."	( Effects of caffeine on intracellular calcium, calcium current and calcium-dependent potassium current in anterior pituitary GH3 cells. Kramer, RH; Levitan, ES; Mokkapatti, R, 1994)	1.4
"Caffeine has a more pronounced effect on phase 2A (16-36 min) than on phase 2, with significant effects being observed at lower doses."	( Caffeine antinociception: role of formalin concentration and adenosine A1 and A2 receptors. Reid, A; Sawynok, J, 1996)	2.46
"Caffeine has an ergogenic effect on endurance performance in dosages of 3 to 6 mg/kg."	( [The use of drugs to improve athletic performance]. Hartgens, F; Kuipers, H, 1997)	1.02
"Caffeine has a DNA-repair inhibiting effect."	( Caffeine-assisted chemotherapy and minimized tumor excision for nonmetastatic osteosarcoma. Asada, N; Kitano, S; Mori, Y; Morinaga, T; Tomita, K; Tsuchiya, H; Yamamoto, N, )	2.3
"Caffeine has a variety of pharmacological effects. "	( Caffeine for asthma. Bara, AI; Barley, EA, 2000)	3.19
"Caffeine, which has a DNA-repair inhibiting effect, enhances the cytocidal effects of anticancer drugs and radiation. "	( Caffeine-potentiated radiochemotherapy and function-saving surgery for high-grade soft tissue sarcoma. Asada, N; Kanazawa, Y; Nishijima, H; Takanaka, T; Terasaki, T; Tomita, K; Tsuchiya, H; Yamamoto, N, )	3.02
"Caffeine has a synergistic effectiveness with analgesics. "	( Do caffeine-containing analgesics promote dependence? A review and evaluation. Dalessio, D; Feinstein, AR; Fox, JM; Goldstein, J; Haag, G; Heinemann, LA; Ladewig, D; O'Brien, CP, 2000)	2.37
"Caffeine has a variety of pharmacological effects. "	( Caffeine for asthma. Bara, AI; Barley, EA, 2001)	3.2
"Caffeine, which has a wide range between therapeutic and toxic levels, is a widely used medication for prevention and treatment of apnoea of prematurity. "	( Caffeine intoxication in a premature neonate. Aksoy, E; Atalay, Y; Dalgiç, N; Ergenekon, E; Koç, E, 2001)	3.2
"Caffeine has a wide range of behaviorally active properties. "	( Caffeine effects on behavioral thermoregulation. McNeil, MJ; Quinn, JM; Rust, ML; Vitulli, WF, 1991)	3.17
"4) Caffeine consumption has an association with alcohol use and smoking habit among males."	( Caffeine consumption among medical students. Fujimura, T; Mino, Y; Ohara, H; Yasuda, N, 1990)	2.24
"Caffeine also has an inhibitory effect which is partly attributable to decrease in [Ca2+]cyt and partly to the decrease in the sensitivity to Ca2+ of the contractile elements."	( Multiple effects of caffeine on contraction and cytosolic free Ca2+ levels in vascular smooth muscle of rat aorta. Karaki, H; Ozaki, H; Sato, K, 1988)	1.32
"Caffeine has a similar overall effect in control and A-T cell lines in reducing the G2 arrest observed after ionizing radiation."	( Effect of caffeine on gamma-ray-induced G2 delay in ataxia telangiectasia. Bates, PR; Imray, FP; Lavin, MF, 1985)	1.39
"Caffeine, which has an effective partition coefficient that approaches that of thiopental, was used as an indicator substance to estimate the immediate volume of distribution of thiopental."	( Correlation between thiopental induction dose and the volume of distribution of caffeine in human subjects. Bizzarri, DV; DeLaRocha, A; Inchiosa, MA; Milliken, RA; Schmahai, TJ, 1986)	1.22
"Caffeine effects have been overlooked in generalist herbivores that are not specialized in coffee or tea plants."	( Cascading effects of caffeine intake by primary consumers to the upper trophic level. Hance, T; Tougeron, K, 2022)	1.76
"Caffeine has an anti-infectious potential and ameliorated infection-derived inflammation following experimental infection with L. "	( Anti-inflammatory activity of caffeine (1,3,7-trimethylxanthine) after experimental challenge with virulent Listeria monocytogenes in Swiss mice. de Alcântara Almeida, I; Mancebo Dorvigny, B; Nunes Santana, L; Souza Tavares, L; Vitor Lima-Filho, J, 2021)	2.35
"Caffeine intake has been inconsistently associated with the risk of ovarian cancer in previous studies. "	( Lifetime caffeine intake and the risk of epithelial ovarian cancer. Aronson, KJ; Arseneau, J; Gilbert, L; Gotlieb, WH; Grundy, A; Koushik, A; Sandhu, S, 2022)	2.58
"Caffeine has been purported to have anxiogenic and panicogenic properties, specifically salient in patients with panic disorder (PD). "	( Effects of caffeine on anxiety and panic attacks in patients with panic disorder: A systematic review and meta-analysis. Frick, A; Klevebrant, L, )	1.96
"Caffeine has been reported for its antiinflammatory properties by stimulating phagocytosis. "	( Antiinflammatory and antiinfective effect of caffeine in a mouse model of disseminated salmonellosis. da Silva Júnior, VA; de Almeida, IA; de Souza Silva, E; de Souza, JKU; Dorvigny, BM; Lima-Filho, JV; Santana, LN; Soares, AF; Tavares, LS, 2022)	2.42
"Caffeine has been studied as a potentiating agent in chemotherapy against some types of cancer, but there are few reports on its effects on melanoma. "	( Caffeine improves the cytotoxic effect of dacarbazine on B16F10 murine melanoma cells. Bordini, HP; Cecchini, AL; Fagundes, TR; Luiz, RC; Madeira, TB; Marinello, PC; Melo, GP; Nixdorf, SL, 2022)	3.61
"Caffeine consumption has been linked to poor sleep health in adolescents, but it is unknown whether poor sleep predicts caffeine consumption, and/or whether caffeine consumption predicts poor sleep, particularly when sleep is measured objectively. "	( Too Jittery to Sleep? Temporal Associations of Actigraphic Sleep and Caffeine in Adolescents. Buxton, OM; Chang, AM; Hale, L; Master, L; Mathew, GM; Reichenberger, DA, 2021)	2.3
"Caffeine ingestion has well-established ergogenic effects for resistance exercise performance. "	( Exploring the minimum ergogenic dose of caffeine on resistance exercise performance: A meta-analytic approach. Grgic, J, 2022)	2.43
"Caffeine consumption has been linked to dysfunction of the autonomic nervous system."	( Impact of energy drink versus coffee consumption on periodic repolarization dynamics: an interventional study. Bauer, A; Brunner, S; Hamm, W; Rudi, WS; Schüttler, D, 2022)	1.44
"Caffeine has a significant effect on cerebrovascular systems, and the dual action of caffeine on both neural and vascular responses leads to concerns for the interpretation of blood oxygenation level-dependent (BOLD) functional MRI. "	( Cerebral hemodynamic response to caffeine: effect of dietary caffeine consumption. Chu, LWL; Peng, SL; Su, FY, 2022)	2.45
"Caffeine has well established effects for promoting both physical and cognitive performance, but the translation of such benefits specifically for soccer match play is not well established."	( The Effect of Acute Caffeine Ingestion on Tactical Performance of Professional Soccer Players. Aquino, R; Clarke, ND; da Costa, IT; de Almeida, RF; Guimaraes-Ferreira, L; Machado, G; Rinaldi, NM; Tallis, J, 2022)	1.77
"Caffeine citrate has therapeutic effect on different brain diseases, while its role in SAE remains unclear."	( Caffeine Citrate Protects Against Sepsis-Associated Encephalopathy and Inhibits the UCP2/NLRP3 Axis in Astrocytes. Chen, P; Cheng, Y; Hu, J; Huang, Z; Yang, L, 2022)	2.89
"Oral caffeine intake has been deemed as an effective supplementation strategy to enhance fat oxidation during aerobic exercise with a steady-state intensity. "	( Caffeine increases exercise intensity and energy expenditure but does not modify substrate oxidation during 1 h of self-paced cycling. Amaro-Gahete, FJ; Del Coso, J; Giráldez-Costas, V; González-García, J; Gutiérrez-Hellín, J; Mañas, A; Ruiz-Moreno, C, 2022)	2.68
"Caffeine has known effects on the central nervous and cardiovascular systems. "	( Quantitative probabilistic assessment of caffeine intake from tea in Chinese adult consumers based on nationwide caffeine content determination and tea consumption survey. Li, J; Song, J; Song, Y; Sui, H; Tan, R; Wei, S; Xiao, X; Xu, H; Yang, X; Yong, L, 2022)	2.43
"Caffeine has been used as a first-line drug for treatment of apnea neonatorum for decades due to its high safety and effectiveness. "	( Caffeine excites medial parabrachial nucleus neurons of mice by blocking adenosine A1 receptor. Cai, X; Chen, J; Gyabaah, AT; Huang, ZL; Li, Y; Li, Z; Ma, C; Shi, H; Tu, Y; Yu, C, 2022)	3.61
"Caffeine has been shown to maintain hepatoprotective effect with an unclear mechanism."	( Caffeine alleviates acute liver injury by inducing the expression of NEDD4L and deceasing GRP78 level via ubiquitination. Cao, LP; Fu, YM; Hu, XW; Li, J; Li, XM; Long, H; Wang, AM; Xiong, YH; Xu, J; Zeng, F; Zhang, FJ, 2022)	2.89
"Caffeine has been shown to improve these measures but also results in increased blood pressure and jitteriness."	( Effects of caffeine, methylliberine, and theacrine on vigilance, marksmanship, and hemodynamic responses in tactical personnel: a double-blind, randomized, placebo-controlled trial. Arent, SM; Bello, ML; Cardaci, TD; Chandler, AJ; Cintineo, HP; McFadden, BA, 2022)	1.83
"Caffeine has beneficial effects on firefighter job performance reducing fatigue and improving psychomotor vigilance. "	( Cardiometabolic Biomarkers and Habitual Caffeine Consumption Associate with the Adverse Ambulatory Blood Pressure Response to Strenuous Physical Exertion among Firefighters. Berkowsky, RS; Chen, MH; Fernandez, AB; Gans, KM; Parducci, PM; Pescatello, LS; Taylor, BA; Wu, Y; Zaleski, AL; Zhang, Y, 2022)	2.43
"Caffeine has been proposed as a secondary treatment to relieve PD symptoms mainly by its antagonistic effects on adenosine receptors (ARs)."	( Caffeine improves mitochondrial function in PINK1 Dalla Corte, CL; Foletto, JVP; Gonçalves, DF; Michelotti, P; Senger, LR; Soares, FAA, 2023)	3.07
"Caffeine has long been vilified as a cause for urinary urgency incontinence (UUI) along with other potential bladder irritants such as carbonation, alcohol, and acidic juices. "	( Total fluid intake, caffeine, and other bladder irritant avoidance among adults having urinary urgency with and without urgency incontinence: The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN). Amundsen, CL; Cameron, AP; Clemens, JQ; Gillespie, BW; Helmuth, ME; Kirkali, Z; Lai, HH; Smith, AR; Yang, CC, 2023)	2.68
"Caffeine has favorable effects on the metabolic syndrome, chiefly reducing obesity and insulin resistance."	( Systematic review of the effect of caffeine therapy effect on cardiometabolic markers in rat models of the metabolic syndrome. Al Ansari, AM; Alabbasi, AMA; Alhadi, IA; AlSaleh, AFF, 2023)	1.91
"Caffeine has been reported toxic to aquatic organisms, and it frequently occurs at relatively high concentrations in most of surface waters. "	( A Tiered Ecological Risk Assessment of Caffeine by Using Species Sensitivity Distribution Method in the Nansi Lake Basin. Dong, L; Li, L; Ling, J; Wang, S; Wu, Y; Yang, W; Yin, Y; Zhang, J; Zhang, Y; Zheng, L, 2023)	2.62
"Caffeine (CAF) has been considered an emerging environmental contaminant and its presence indicator of anthropogenic contamination. "	( Effects of environmental concentrations of caffeine on adult zebrafish behaviour: a short-term exposure scenario. Domingues, I; Grisolia, CK; Oliveira, M; Perillo, V; Picolo, V; Santos, N; Villacis, RAR, 2023)	2.62
"Caffeine has a wide range of effects in humans and other organisms. "	( Caffeine activates HOG-signalling and inhibits pseudohyphal growth in Saccharomyces cerevisiae. Blomberg, A; Elhasi, T, 2023)	3.8
"Caffeine has both positive and negative effects on this population and further research is necessary to better understand the long-term consequences of caffeine consumption."	( Caffeine addiction and determinants of caffeine consumption among health care providers: a descriptive national study. Abdullah, DM; AlAmri, FA; Alenezi, MA; AlRadini, FA; Amer, SA; Elsayed, M; Fagehy, AA; Shah, J; Shajeri, GM; Zaitoun, NA, 2023)	3.07
"Caffeine has long been used as a stimulant by humans. "	( Caffeine Consumption Helps Honey Bees Fight a Bacterial Pathogen. Arnott, RLW; Moran, NA; Motta, EVS, 2023)	3.8
"Caffeine has been suggested to regulate cerebrospinal fluid secretion and is known both to alleviate and to trigger headache; however, its effect on the regulation of intracranial pressure (ICP) is not known."	( Effects of caffeine on intracranial pressure and pain perception in freely moving rats. Eftekhari, S; Israelsen, IME; Jensen, RH; Kamp-Jensen, C; Westgate, CSJ, 2023)	2.02
"Caffeine has been found to interfere with the quorum sensing of P."	( Inhibition of biofilm formation of Pseudomonas aeruginosa by caffeine: a potential approach for sustainable management of biofilm. Basu, D; Basu, S; Chakraborty, P; Dastidar, DG; Dutta, S; Paul, P; Sarkar, A; Sarker, RK; Sen, A; Sharma, SR; Tribedi, P, 2020)	1.52
"Caffeine has been shown to directly increase fatty acid oxidation, in part, by promoting mitochondrial biogenesis. "	( Low-dose caffeine administration increases fatty acid utilization and mitochondrial turnover in C2C12 skeletal myotubes. Baumgarner, BL; Brown, SL; Crocker, CL; Cutrone, M; Dintino, MM; Enyart, DS; Kinsey, ST; Stansell, JR, 2020)	2.42
"Caffeine also has the potential benefit of improving vigilance and attention during sustained operations offering little opportunity for sleep."	( A Systematic Review of the Effect of Dietary Supplements on Cognitive Performance in Healthy Young Adults and Military Personnel. Kemps, E; Pomeroy, DE; Probert, B; Tooley, KL; Wilson, A, 2020)	1.28
"Caffeine intake has also shown ergogenic effects, which are attributed to different factors, such as enhanced substrate utilization, fatigue delay, and alertness."	( Caffeine effects on systemic metabolism, oxidative-inflammatory pathways, and exercise performance. Barcelos, RP; Bresciani, G; Carvalho, NR; Lima, FD; Royes, LF, 2020)	2.72
"Caffeine mouth rinsing has emerged as an alternative to oral caffeine consumption for improving performance without provoking lower gastrointestinal distress. "	( Acute Caffeine Mouth Rinse Does Not Change the Hydration Status following a 10 km Run in Recreationally Trained Runners. Figueiredo, N; Gentil, P; Gonzalez, AM; Guimarães, V; Mota, JF; Pimentel, GD; Queiroz, M, 2020)	2.48
"Caffeine has been known to combat stress-evoked depression."	( New insights into the effects of caffeine on adult hippocampal neurogenesis in stressed mice: Inhibition of CORT-induced microglia activation. He, RR; Kurihara, H; Li, WX; Li, YF; Luo, Z; Mao, ZF; Ouyang, SH; Tu, LF; Wang, GE; Wu, YP; Zhang, QY, 2020)	1.56
"Caffeine has an anti-obesity effect, although chronic excessive caffeine consumption also causes caffeinism, which is marked by increased anxiety or depression, amongst other symptoms. "	( Astilbin lowers the effective caffeine dose for decreasing lipid accumulation via activating AMPK in high-fat diet-induced obese mice. Yang, L; Zheng, G; Zhong, S; Zhu, Y, 2021)	2.35
"Caffeine has been demonstrated to enhance olfactory function in rodents, but to date, the sparse research in humans has not shown any equivalent effects. "	( The effects of caffeine on olfactory function and mood: an exploratory study. Orgill, K; Stafford, LD, 2020)	2.35
"Caffeine has wide interindividual pharmacodynamic variability and a wide therapeutic index in preterm newborns."	( Pharmacokinetics, pharmacodynamics and metabolism of caffeine in newborns. Aranda, JV; Beharry, KD, 2020)	1.53
"3. Caffeine has consistently been shown to improve exercise performance when consumed in doses of 3-6 mg/kg body mass."	( International society of sports nutrition position stand: caffeine and exercise performance. Antonio, J; Arent, SM; Campbell, BI; Goldstein, ER; Grgic, J; Guest, NS; Jenkins, NDM; Kalman, DS; Nelson, MT; Schoenfeld, BJ; Smith-Ryan, AE; Stout, JR; Trexler, ET; VanDusseldorp, TA, 2021)	1.38
"Caffeine has developmental toxicity. "	( Prenatal caffeine exposure caused H-type blood vessel-related long bone dysplasia via miR375/CTGF signaling. Chen, L; He, H; Liu, L; Luo, H; Shangguan, Y; Wang, H; Wen, Y; Xie, X, 2021)	2.48
"Caffeine has been associated with reduced rates of acute kidney injury (AKI) in preterm neonates. "	( Renal tissue oxygenation after caffeine administration in preterm neonates. Adegboro, CO; Harer, MW; McAdams, RM; Richard, LJ; Rothwell, AC, 2021)	2.35
"Caffeine has been proven to be an effective anti-inflammatory and immunomodulator."	( Possible Beneficial Actions of Caffeine in SARS-CoV-2. Flores-Soto, E; Montaño, LM; Pérez-Figueroa, GE; Ramírez-Salinas, GL; Romero-Martínez, BS; Solís-Chagoyán, H; Sommer, B, 2021)	1.63
"Caffeine intake has been demonstrated to influence several physiological measures, including some related to eye physiology. "	( Short-term effects of caffeine intake on binocular accommodative facility: a quantitative and qualitative analysis. Jiménez, R; Koulieris, GA; Molina-Romero, R; Redondo, B; Vera, J, 2022)	2.48
"Caffeine has been identified as emerging contaminant of concern due to its widespread occurrence in the aquatic environment and potential to be biologically active. "	( Caffeine as a contaminant of concern: A review on concentrations and impacts in marine coastal systems. Freitas, R; Soares, AMVM; Vieira, LR, 2022)	3.61
"Caffeine has been shown to be a robust uncompetitive inhibitor of glucose uptake in erythrocytes. "	( Caffeine inhibition of GLUT1 is dependent on the activation state of the transporter. Busscher, BM; Gunnink, LK; Looyenga, BD; Louters, LL; Rosette, KA; Strohbehn, LE; Wodarek, JA, 2017)	3.34
"Caffeine has been ascribed to positive effects on airway inflammation as well as remodeling."	( Caffeine modulates glucocorticoid-induced expression of CTGF in lung epithelial cells and fibroblasts. Fehrholz, M; Glaser, K; Kunzmann, S; Ottensmeier, B; Seidenspinner, S; Speer, CP, 2017)	2.62
"Caffeine has multiple actions including blockade of adenosine receptors."	( Caffeine accelerates recovery from general anesthesia via multiple pathways. Chowdhury, AN; Fong, R; Fox, AP; Khokhar, S; Wong, JH; Xie, KG; Xie, Z, 2017)	2.62
"Caffeine has shown potential inhibitory effect against epithelial cancer."	( Virtual Screening and Statistical Analysis in the Design of New Caffeine Analogues Molecules with Potential Epithelial Anticancer Activity. Cruz, JV; da Cruz Macedo, WJ; da Silva Costa, J; da Silva Lopes Costa, K; da Silva Ramos, R; de Paula da Silva, CHT; Do Socorro Barros Brasil, D; Dos Santos, CBR; Silva, LB, 2018)	1.44
"Caffeine intake has been associated with a range of reversible and transient physiological effects broadly and cardiovascular effects specifically."	( Caffeine and cardiovascular health. Chowdhury, F; Mariano, GF; Rodricks, JV; Turnbull, D, 2017)	2.62
"Caffeine has been identified to have beneficial effects against chronic liver diseases, particularly liver fibrosis. "	( Autophagy mediated by endoplasmic reticulum stress enhances the caffeine-induced apoptosis of hepatic stellate cells. Chen, Y; Huang, H; Kuang, J; Li, Y; Shi, M; Yan, J; Yang, W, 2017)	2.14
"Caffeine intake has been associated with a lower risk of Parkinson's disease (PD). "	( Differences in Parkinson's Disease Risk with Caffeine Intake and Postmenopausal Hormone Use. Ascherio, A; Gao, X; Hughes, KC; Kim, IY; O'Reilly, ÉJ; Schwarzschild, MA, 2017)	2.16
"Caffeine has the ability to release catecholamines, but its effects after exercises is little explored."	( Caffeine affects autonomic control of heart rate and blood pressure recovery after aerobic exercise in young adults: a crossover study. Gomes, RL; Gonzaga, LA; Valenti, VE; Vanderlei, LCM, 2017)	2.62
"Caffeine has anti-inflammation, antihepatic steatosis, and anti-insulin resistance effects."	( Effects and mechanisms of caffeine to improve immunological and metabolic abnormalities in diet-induced obese rats. Hou, MC; Hsieh, YC; Huang, CC; Huang, SF; Lee, FY; Lee, KC; Lee, SD; Li, TH; Lin, HC; Lin, MW; Liu, CW; Su, YB; Tsai, CY; Tsai, HC; Yang, YY, 2018)	1.5
"Caffeine has been shown to enhance the speed of recovery from general anesthesia in murine models, though data in human patients is lacking. "	( Effects of caffeine administration on sedation and respiratory parameters in patients recovering from anesthesia. Schroeder, DR; Sprung, J; Warner, MA; Warner, NS; Weingarten, TN, 2018)	2.31
"Caffeine has a well-established effect on reaction times (RTs) but the neurocognitive mechanisms underlying this are unclear."	( Effects of caffeine on reaction time are mediated by attentional rather than motor processes. de Morree, HM; Dundon, NM; Klein, C; Marcora, SM; Saville, CWN, 2018)	2.31
"Caffeine intake has been inversely associated with Parkinson's disease (PD) risk. "	( Interaction between caffeine and polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2) on Parkinson's disease risk. Ascherio, A; Betensky, RA; Gao, X; Hannan, MT; Hughes, KC; Kim, IY; McCullough, ML; O'Reilly, ÉJ; Schwarzschild, MA, 2018)	2.25
"Caffeine consumption has increased in recent years and especially in French Army."	( Severe Sympathomimetic Toxidrome in a French Soldier: How Caffeine Overdose Can Lead to Severe Consequences. Delacour, H; Dubost, C; Lahutte, B; Laitselart, P; Plantamura, J; Saguin, E, 2018)	1.45
"Caffeine has been described as a sports performance-enhancing substance. "	( Caffeine Consumption Is Associated With Higher Level of Physical Activity in Japanese Women. Gando, Y; Hara, H; Kawakami, R; Miyachi, M; Miyatake, N; Murakami, H; Ohno, H; Tripette, J, 2018)	3.37
"Caffeine withdrawal has been included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), but caffeine use disorder (CUD) is considered to be a condition for further study."	( Caffeine use disorder: An item-response theory analysis of proposed DSM-5 criteria. Ágoston, C; Demetrovics, Z; Richman, MJ; Urbán, R, 2018)	2.64
"Caffeine has already been proposed as an anthropogenic marker for wastewater contamination of surface waters."	( Caffeine levels as a predictor of Human mastadenovirus presence in surface waters-a case study in the Sinos River basin-Brazil. Antunes, MV; Bündchen, R; da Rosa, DC; Demoliner, M; Fleck, JD; Girardi, V; Kael, IM; Krajeski, DM; Linden, R; Peteffi, GP; Silva, FP, 2018)	2.64
"Caffeine has a small but evident effect on endurance performance when taken in moderate doses (3-6 mg/kg) as well as an overall improvement following caffeine compared to placebo in mean power output (3.03 ± 3.07%; effect size = 0.23 ± 0.15) and time-trial completion time (2.22 ± 2.59%; effect size = 0.41 ± 0.2)."	( The Effect of Acute Caffeine Ingestion on Endurance Performance: A Systematic Review and Meta-Analysis. Ali, A; Rutherfurd-Markwick, KJ; Southward, K, 2018)	1.53
"Caffeine has been frequently detected in agriculture produce; however, little attention is given to its metabolites in vegetables."	( Metabolic Demethylation and Oxidation of Caffeine during Uptake by Lettuce. Boyd, SA; Chuang, YH; Hammerschmidt, R; Li, H; Liu, CH; Zhang, W, 2018)	1.47
"Caffeine has been considered a trigger for atrial fibrillation (AF). "	( Does Caffeine Consumption Increase the Risk of New-Onset Atrial Fibrillation? Abdelfattah, R; Kamran, H; Kassotis, J; Lazar, J, 2018)	2.44
"Caffeine consumption has been widely used as a central nervous system stimulant. "	( Caffeine consumption during early pregnancy impairs oviductal embryo transport, embryonic development and uterine receptivity in mice. Chen, Q; Duan, E; Hwang, SJ; Kim, BH; Liu, S; Qian, J; Qu, Y; Shi, J; Ward, SM; Zhang, L; Zhang, X; Zhang, Y; Zhou, T, 2018)	3.37
"Caffeine has a very favorable benefit-to-risk ratio, and has become one of the most prescribed and cost-effective pharmacotherapies in the NICU."	( Caffeine: an evidence-based success story in VLBW pharmacotherapy. Dobson, NR; Hunt, CE, 2018)	2.64
"Caffeine has been considered a neuroprotective agent against Parkinson's disease (PD). "	( Biomarker repurposing: Therapeutic drug monitoring of serum theophylline offers a potential diagnostic biomarker of Parkinson's disease. Ishii, R; Kasai, T; Kosaka, T; Mizuno, T; Ohmichi, T; Shikata, K; Shinomoto, M; Tatebe, H; Tokuda, T, 2018)	1.92
"Caffeine has similar effects on cardiac parameters as aminophylline; however, caffeine-treated small-for-gestation stratification gave rise to significant cardiac variations."	( Acute hemodynamic effects of methylxanthine therapy in preterm neonates: Effect of variations in subgroups. Kamath, A; Lewis, LES; M, S; Nayak, K; Purkayastha, J, 2019)	1.96
"Caffeine has well-documented benefits on endurance athletic performance. "	( Establishing a relationship between the effect of caffeine and duration of endurance athletic time trial events: A systematic review and meta-analysis. Brooks, MB; Cincotta, J; Manjourides, JD; Shen, JG, 2019)	2.21
"Caffeine has a strong antagonistic effect against theanine."	( Stress-Reducing Function of Matcha Green Tea in Animal Experiments and Clinical Trials. Furushima, D; Hamamoto, S; Horie, H; Iguchi, K; Morita, A; Nakamura, Y; Unno, K; Yamada, H, 2018)	1.2
"Caffeine has a well-established effect on intraocular pressure (IOP) and ocular perfusion pressure (OPP); however, the possible differences between low- and high-caffeine consumers remain unknown."	( Effects of caffeine on intraocular pressure are subject to tolerance: a comparative study between low and high caffeine consumers. Bermúdez, J; Jiménez, R; Molina, R; Redondo, B; Vera, J, 2019)	2.35
"Caffeine has been proposed, based on in vitro cultured cell studies, to accelerate progression of autosomal dominant polycystic kidney disease (ADPKD) by increasing kidney size. "	( Relationship between caffeine intake and autosomal dominant polycystic kidney disease progression: a retrospective analysis using the CRISP cohort. Bae, KT; Bennett, WM; Chapman, AB; El Ters, M; Harris, PC; Landsittel, DP; Mahnken, JD; McKenzie, KA; Mrug, M; Rahbari-Oskoui, FF; Torres, VE; Yu, ASL, 2018)	2.24
"Caffeine has been shown to enhance strength, power and endurance, characteristics that underpin performance in rugby. "	( Effect of caffeinated gum on a battery of rugby-specific tests in trained university-standard male rugby union players. Boyd, C; Lynn, A; Parry, A; Parsons, M; Pratt, H; Ranchordas, MK, 2019)	1.96
"Caffeine consumption has been associated with loss of body weight and increased energy expenditure, but whether it can activate UCP1 is unknown."	( Caffeine exposure induces browning features in adipose tissue in vitro and in vivo. Bloor, I; Budge, H; Law, J; Leija, HAL; Morris, DE; Sacks, H; Sottile, V; Symonds, ME; Velickovic, K; Wayne, D, 2019)	2.68
"Caffeine ingestion has also demonstrated positive effects on sprint performance."	( Effects of caffeine and carbohydrate mouth rinses on repeated sprint performance. Beaven, CM; Cook, C; Kilduff, L; Maulder, P; Pooley, A, 2013)	1.5
"Caffeine consumption has been related to loss of body weight and modulates lipid metabolism. "	( Caffeine inhibits adipogenic differentiation of primary adipose-derived stem cells and bone marrow stromal cells. Chen, KM; Shyu, HW; Su, SH; Su, SJ; Yeh, H; Yeh, YT, 2013)	3.28
"Caffeine consumption has been receiving increased interest from both the medical and lay press, especially given the increased amounts now available in energy products. "	( Caffeine reduces myocardial blood flow during exercise. Babu, KM; Higgins, JP, 2013)	3.28
"Caffeine and aspirin have been suggested to be involved in neurologic diseases, such as schizophrenia, and previous data have revealed that abnormal expression of HERV-W elements may be an important factor in the etiopathogenesis of those diseases. "	( Activation of elements in HERV-W family by caffeine and aspirin. Chen, Y; Li, S; Liu, C; Wang, X; Yu, H; Zeng, J; Zhu, F, 2013)	2.1
"Caffeine has been used as a scaffold for the design of inhibitors of monoamine oxidase (MAO) A and B. "	( The interactions of caffeine with monoamine oxidase. Petzer, A; Petzer, JP; Pienaar, A, 2013)	2.16
"Caffeine intake has also been proposed to increase symptomatic warning signs of hypoglycemia in patients with type 1 diabetes and elevate blood glucose levels in patients with type 2 diabetes."	( Caffeine and glucose homeostasis during rest and exercise in diabetes mellitus. Riddell, MC; Zaharieva, DP, 2013)	2.55
"Caffeine has attracted abundant attention due to its extensive existence in beverages and medicines. "	( Make caffeine visible: a fluorescent caffeine "traffic light" detector. Agrawalla, BK; Chang, YT; Cho, YK; Er, JC; Kale, AA; Kim, TH; Xu, W; Zhai, D; Zhang, L, 2013)	2.35
"Caffeine also has an effect on the central nervous system (CNS), and it is now recognized that most of the performance-enhancing effect of caffeine is accomplished through the antagonism of the adenosine receptors, influencing the dopaminergic and other neurotransmitter systems."	( Caffeine, exercise and the brain. Meeusen, R; Roelands, B; Spriet, LL, 2013)	2.55
"Caffeine exposure has been associated with increased risk of AF, but heterogeneous data exist in the literature."	( Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies. Alves, LB; Caldeira, D; Costa, J; Ferreira, JJ; Martins, C; Pereira, H, 2013)	2.55
"Caffeine has been widely used in sports competitions due to its ergogenic effects. "	( Caffeine supplementation modulates oxidative stress markers in the liver of trained rats. Amaral, GP; Barbosa, NV; Barcelos, RP; Bresciani, G; Fighera, MR; Soares, FA; Souza, MA; Stefanello, ST, 2014)	3.29
"Caffeine has been reported to produce many beneficial effects for health."	( Moderate swimming exercise and caffeine supplementation reduce the levels of inflammatory cytokines without causing oxidative stress in tissues of middle-aged rats. Bresciani, G; Carvalho, NR; Cechella, JL; da Rocha, JT; Dobrachinski, F; Duarte, MM; Leite, MR; Royes, LF; Soares, FA; Zeni, G, 2014)	1.41
"Mean caffeine intake has not increased among children and adolescents in recent years. "	( Trends in caffeine intake among U.S. children and adolescents. Branum, AM; Rossen, LM; Schoendorf, KC, 2014)	1.32
"Caffeine has been an integral component of our diet and medicines for centuries. "	( Excess caffeine exposure impairs eye development during chick embryogenesis. Cheng, X; Chuai, M; Kurihara, H; Lee, KK; Ma, ZL; Wang, G; Yang, X, 2014)	2.3
"Caffeine has been shown to alter neuronal functioning through increasing spontaneous firing."	( Chronic caffeine ingestion causes microglia activation, but not proliferation in the healthy brain. Brumberg, JC; Intrabartolo, L; Kamal, A; Lutchman, S; Sohail, R; Steger, R, 2014)	1.56
"Caffeine has already been used as an indicator of anthropogenic impacts, especially the ones related to the disposal of sewage in water bodies. "	( Caffeine as an indicator of estrogenic activity in source water. Jardim, WF; Montagner, CC; Pasquini, C; Umbuzeiro, GA, 2014)	3.29
"Caffeine has been shown to promote calcium-dependent activation of AMP-activated protein kinase (AMPK) and AMPK-dependent glucose and fatty acid uptake in mammalian skeletal muscle. "	( Caffeine promotes autophagy in skeletal muscle cells by increasing the calcium-dependent activation of AMP-activated protein kinase. Baumgarner, BL; Downs, RM; Ferris, RK; Kinsey, ST; Mathew, TS, 2014)	3.29
"Caffeine has been described as a modulator of cellular metabolism."	( Dose-dependent effects of caffeine in human Sertoli cells metabolism and oxidative profile: relevance for male fertility. Alves, MG; Barros, A; Bernardino, RL; Dias, TR; Martins, AD; Moreira, AC; Oliveira, PF; Silva, BM; Silva, J; Sousa, M, 2015)	1.44
"Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and aspirin, in the belief that it enhances analgesic efficacy."	( Caffeine as an analgesic adjuvant for acute pain in adults. Derry, CJ; Derry, S; Moore, RA, 2014)	2.57
"Caffeine has been noted for its effects on liver inflammation, fibrogenesis, and vasoreactiveness."	( Caffeine ameliorates hemodynamic derangements and portosystemic collaterals in cirrhotic rats. Chang, CC; Chuang, CL; Ho, HL; Hsin, IF; Hsu, SJ; Huang, HC; Lee, FY; Lee, SD; Lin, HC; Lin, TY; Wang, SS, 2015)	2.58
"Caffeine has a preventive effect on ALF."	( Caffeine protects against alcohol-induced liver fibrosis by dampening the cAMP/PKA/CREB pathway in rat hepatic stellate cells. Dai, X; Li, J; Lv, X; Wang, H; Wang, Q; Yang, F; Yang, W; Yang, Y; Zhao, H, 2015)	2.58
"Caffeine has been hypothesized as a risk factor for SAB since the 1980s; however, results from previous studies have been conflicting."	( Caffeine and caffeinated beverage consumption and risk of spontaneous abortion. Brogly, SB; Hahn, KA; Hatch, EE; Mikkelsen, EM; Riis, AH; Rothman, KJ; Sørensen, HT; Wise, LA, 2015)	3.3
"Caffeine consumption has been associated to decreased levels of liver enzymes and lower risk of fibrosis in patients with hepatitis C virus. "	( Association of caffeine intake and liver fibrosis in patients with chronic hepatitis C. Buss, C; Oliveira, Kda S; Tovo, CV, )	1.93
"Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied."	( Coffee Consumption and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Sex: The Liver Cancer Pooling Project. Alavanja, MC; Beane-Freeman, LE; Boggs, DA; Buring, JE; Campbell, PT; Chan, AT; Chong, DQ; Freedman, ND; Fuchs, CS; Gapstur, SM; Gaziano, JM; Giovannucci, EL; Graubard, BI; Hollenbeck, AR; King, LY; Koshiol, J; Lai, GY; Lee, IM; Linet, MS; McGlynn, KA; Palmer, JR; Petrick, JL; Poynter, JN; Purdue, MP; Robien, K; Sahasrabuddhe, VV; Schairer, C; Sesso, HD; Sigurdson, AJ; Wactawski-Wende, J; Zeleniuch-Jacquotte, A, 2015)	1.14
"Caffeine has been shown to prevent ultraviolet radiation-induced carcinogenesis and to inhibit growth of melanoma cells in experimental studies. "	( Caffeine Intake, Coffee Consumption, and Risk of Cutaneous Malignant Melanoma. Cho, E; Gao, X; Han, J; Hunter, DJ; Qureshi, AA; Song, F; Wu, S, 2015)	3.3
"Caffeine has shown effectiveness for treating PDPH, decreasing the proportion of participants with PDPH persistence and those requiring supplementary interventions, when compared with placebo."	( Drug therapy for treating post-dural puncture headache. Basurto Ona, X; Bonfill Cosp, X; Osorio, D, 2015)	1.14
"Caffeine has been shown to improve endurance exercise performance, but results are mixed in the context of strength and sprint performance."	( Creatine and Caffeine: Considerations for Concurrent Supplementation. Smith-Ryan, AE; Trexler, ET, 2015)	1.51
"Caffeine has been proposed to have several beneficial effects on obesity and its related metabolic diseases; however, how caffeine affects adipocyte differentiation has not been elucidated. "	( Caffeine inhibits adipogenesis through modulation of mitotic clonal expansion and the AKT/GSK3 pathway in 3T3-L1 adipocytes. Choi, H; Choi, Y; Kim, A; Kim, AR; Kim, JW; Park, H; Seok, JW; Song, SJ; Yoon, BK; Yu, JH, 2016)	3.32
"Caffeine has long been recognized as an addictive substance that causes autonomic nerve effect, and is known to increase catecholamine secretion from the adrenal glands. "	( Non specific drug distribution in an autopsy case report of fatal caffeine intoxication. Endoh, M; Ishikawa, T; Yuasa, I, 2015)	2.1
"Caffeine has been the subject of more scientific safety studies than any other food ingredient."	( Neurobehavioral hazard identification and characterization for caffeine. Mariano, GF; Rodricks, JV; Turnbull, D, 2016)	1.4
"Caffeine has both positive and negative effects on physiological functions in a dose-dependent manner. "	( Caffeine Induces the Stress Response and Up-Regulates Heat Shock Proteins in Caenorhabditis elegans. Al-Amin, M; Gong, J; Kawasaki, I; Shim, YH, 2016)	3.32
"Caffeine consumption has been increasing rapidly in adolescents; however, most research on the behavioral effects of caffeine has been conducted in adults. "	( Chronic caffeine produces sexually dimorphic effects on amphetamine-induced behavior, anxiety and depressive-like behavior in adolescent rats. Dixon, RS; Hickman, ET; Lee, SM; Townsend, SE; Turgeon, SM, 2016)	2.31
"Caffeine has been demonstrated to have a protective effect on neonatal viability of piglets. "	( Effects of oral administration of caffeine on some physiological parameters and maternal behaviour of sows at farrowing. Cavalli, V; Farina, E; Riccardi, E; Sabbioni, A; Saleri, R; Superchi, P, 2016)	2.16
"Caffeine has also effects on the reward system but it seems that this effect does not involve dopaminergic system."	( Molecular and pharmacodynamic interactions between caffeine and dopaminergic system. Coman, O; Fulga, I; Ghiță, I; Segărceanu, A; Voiculescu, M, 2014)	1.38
"Caffeine has been shown to have effects on certain areas of cognition, but in executive functioning the research is limited and also inconsistent. "	( Investigating the effects of caffeine on executive functions using traditional Stroop and a new ecologically-valid virtual reality task, the Jansari assessment of Executive Functions (JEF(©)). Chapman, E; Jansari, AS; Lavan, N; Soar, K; Turner, JJ, 2016)	2.17
"Caffeine consumption has a well-known diuretic effect."	( [Mechanisms of caffeine-induced diuresis]. Jouret, F; Marx, B; Scuvée, É; Scuvée-Moreau, J; Seutin, V, 2016)	1.51
"Caffeine has cognitive-enhancing properties with effects on learning and memory, concentration, arousal and mood. "	( Caffeine-mediated BDNF release regulates long-term synaptic plasticity through activation of IRS2 signaling. Ballesteros, JJ; Burks, D; Fernández, M; Gómez Lázaro, M; Lao-Peregrín, C; Martín, ED; Pérez-Navarro, E; Saavedra, A; Zamora-Moratalla, A, 2017)	3.34
"Caffeine has both excitatory and vasoconstrictive effects on central nervous system. "	( Caffeine discontinuation improves acute migraine treatment: a prospective clinic-based study. Choi, H; Choi, HA; Chung, CS; Lee, MJ, 2016)	3.32
"Caffeine has been shown to have protective actions against AD and based on our recent findings that caffeine can inhibit endocytosis in neurons and can prevent neuronal Aβ generation, we tested the hypothesis that caffeine blocks HIV-1 Tat-induced Aβ generation and tau phosphorylation."	( Caffeine Blocks HIV-1 Tat-Induced Amyloid Beta Production and Tau Phosphorylation. Chen, X; Geiger, JD; Soliman, ML, 2017)	2.62
"As caffeine has been shown to be beneficial for diabetes, obesity and tau phosphorylation, we, therefore, used it as therapeutic treatment."	( Tau hyperphosphorylation in the brain of ob/ob mice is due to hypothermia: Importance of thermoregulation in linking diabetes and Alzheimer's disease. Calon, F; El Khoury, NB; Gratuze, M; Julien, C; Marcouiller, F; Marette, A; Morin, F; Planel, E; Turgeon, A; Whittington, RA, 2017)	0.97
"Caffeine has been found to influence the energy balance by increasing EE and decreasing EI, therefore, it can potentially be useful as a body weight regulator."	( The effect of caffeine on energy balance. Harpaz, E; Tamir, S; Weinstein, A; Weinstein, Y, 2017)	1.54
"Caffeine treatment has reduced cell monolayer permeability after exposure to high glucose and desferoxamine as shown by TEER and FITC-dextran permeability assays."	( Caffeine Prevents Blood Retinal Barrier Damage in a Model, In Vitro, of Diabetic Macular Edema. Cavallaro, S; D'Agata, V; D'Amico, AG; Federico, C; La Cognata, V; Maugeri, G; Rasà, DM; Saccone, S, 2017)	2.62
"Caffeine consumption has been constantly growing in India especially among children and youngsters. "	( Caffeine addiction: Need for awareness and research and regulatory measures. Jain, S; Maggu, G; Srivastava, AS; Verma, RP, 2019)	3.4
"Caffeine has long been used as a pharmacological probe for studying RyR (ryanodine receptor)-mediated Ca(2+) release and cardiac arrhythmias. "	( Caffeine induces Ca2+ release by reducing the threshold for luminal Ca2+ activation of the ryanodine receptor. Chen, SR; Duff, HJ; Jones, PP; Kong, H; Koop, A; Zhang, L, 2008)	3.23
"Caffeine has been identified as belonging to the group of xanthines that enhances the action of cisplatin."	( The antitumor effect of liposome-encapsulated cisplatin on rat osteosarcoma and its enhancement by caffeine. Karita, M; Kasaoka, S; Kawahara, M; Tomita, K; Tsuchiya, H, )	1.07
"Caffeine citrate has been shown to be effective in treating apnea of prematurity."	( Caffeine in children with obstructive sleep apnea. Chuang, AZ; Ganesan, BA; Ghelber, O; Khalil, SN; Maposa, D; Matuszczak, M; Rabb, MF; Tabrizi, HK, 2008)	2.51
"Caffeine has also been reported to inhibit ATM and ATR kinases which leads to the disruption of multiple DNA damage-responsive cell cycle checkpoints and greatly sensitizes tumor cells to antitumor agents which induce genotoxic stress."	( Modulation of cellular response to anticancer treatment by caffeine: inhibition of cell cycle checkpoints, DNA repair and more. Sabisz, M; Skladanowski, A, 2008)	1.31
"Caffeine thus has both pre and postsynaptic sites of action at excitatory synapses."	( Fast inhibition of glutamate-activated currents by caffeine. Smith, SM; Vyleta, NP, 2008)	1.32
"Caffeine has various well-characterized pharmacological effects, but in mammals there are no known plasma membrane receptors or ion channels activated by caffeine. "	( Caffeine activates mouse TRPA1 channels but suppresses human TRPA1 channels. Kubo, Y; Nagatomo, K, 2008)	3.23
"Caffeine has been shown to maintain or improve the performance of individuals, but its pharmacokinetic profile for Asians has not been well characterized. "	( Population pharmacokinetics of caffeine in healthy male adults using mixed-effects models. Fan, W; Fun, CY; Law, YL; Lim, CL; Lim, WM; Seng, KY, 2009)	2.08
"Caffeine has the potential to task this energy equilibrium."	( D-ribose--an additive with caffeine. Herrick, J; Shecterle, LM; St Cyr, JA, 2009)	1.37
"Caffeine has been used by different groups to evaluate the in vivo activity of CYP1A2, NAT2, XO and CYP2A6 in different populations and the effect of many factors on these activities."	( Caffeine metabolic ratios for the in vivo evaluation of CYP1A2, N-acetyltransferase 2, xanthine oxidase and CYP2A6 enzymatic activities. Hakooz, NM, 2009)	2.52
"Caffeine has been used to block unitary potentials, but the ionic conductance responsible for unitary potentials is controversial."	( Caffeine inhibits nonselective cationic currents in interstitial cells of Cajal from the murine jejunum. Jin, NG; Koh, SD; Sanders, KM, 2009)	2.52
"Caffeine has relevance for women's health and pregnancy, including significant associations with spontaneous abortion and low birth weight. "	( Caffeine's implications for women's health and survey of obstetrician-gynecologists' caffeine knowledge and assessment practices. Anderson, BL; Juliano, LM; Schulkin, J, 2009)	3.24
"Caffeine consumption has been equivocally associated with miscarriage, despite an absence of prospective longitudinal measurement of caffeine intake during sensitive windows of human development. "	( Caffeine consumption and miscarriage: a prospective cohort study. Buck Louis, GM; Lum, KJ; Pollack, AZ; Sundaram, R, 2010)	3.25
"Caffeine has been reported to be proconvulsant and to reduce the anticonvulsant efficacy of a variety of antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, valproate and topiramate) in animal models of epilepsy and to increase seizure frequency in patients with epilepsy. "	( Effect of caffeine on the anticonvulsant effects of oxcarbazepine, lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures. Chrościńska-Krawczyk, M; Czuczwar, SJ; Patsalos, PN; Ratnaraj, N, )	1.98
"Caffeine has different effects on the brain, some of which could play a role in brain carcinogenesis, and coffee has been consistently associated with reduced risk of liver cancer, thus suggesting a potential anticarcinogenic effect."	( Coffee, tea, caffeine intake, and risk of adult glioma in three prospective cohort studies. Giovannucci, E; Holick, CN; Michaud, DS; Smith, SG, 2010)	1.45
"Caffeine has a variety of pharmacological effects; it is a weak bronchodilator and it also reduces respiratory muscle fatigue. "	( Caffeine for asthma. Bara, A; Barley, E; Cates, CJ; Welsh, EJ, 2010)	3.25
"Caffeine has also been reported to prevent cognitive decline in healthy subjects but the results of the studies are heterogeneous, some finding no age-related effect while others reported effects only in one sex and mainly in the oldest population."	( Is caffeine a cognitive enhancer? Nehlig, A, 2010)	1.7
"Caffeine has been consumed since ancient times due to its beneficial effects on attention, psychomotor function, and memory. "	( Caffeine and cognition in functional magnetic resonance imaging. Felber, SR; Ischebeck, A; Jaschke, WR; Kolbitsch, C; Koppelstaetter, F; Krause, BJ; Mottaghy, FM; Poeppel, TD; Siedentopf, CM, 2010)	3.25
"Caffeine has well-known short-term stimulating effects on central nervous system, but the long-term impacts on cognition have been less clear. "	( Caffeine as a protective factor in dementia and Alzheimer's disease. Eskelinen, MH; Kivipelto, M, 2010)	3.25
"Caffeine intake has been associated with a decreased risk of Parkinson's disease (PD) in men but the effect in women is less clear, and appears to be modified by use of post-menopausal estrogens. "	( Polymorphisms of caffeine metabolism and estrogen receptor genes and risk of Parkinson's disease in men and women. Ascherio, A; Gao, X; Palacios, N; Schwarzschild, M; Simon, K; Weisskopf, M, 2010)	2.14
"Caffeine has a potential role in promoting alertness during times of desired wakefulness in persons with jet lag or shift work disorder, however its effects on injury and error are unclear."	( Caffeine for the prevention of injuries and errors in shift workers. Blackhall, K; Edwards, PJ; Felix, LM; Ker, K; Roberts, I, 2010)	2.52
"Caffeine has also been recently linked to weight loss and consequent reduction of the overall risks for developing the metabolic syndrome."	( Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. Gonzalez de Mejia, E; Heckman, MA; Weil, J, 2010)	2.52
"Caffeine has been associated with wastewater pollution in temperate and subtropical locations, but environmental caffeine concentrations in tropical locations have not been reported. "	( Caffeine and agricultural pesticide concentrations in surface water and groundwater on the north shore of Kauai (Hawaii, USA). Boehm, AB; Gossett, R; Knee, KL; Paytan, A, 2010)	3.25
"Caffeine has antioxidant properties and has been demonstrated to reduce Abeta levels in transgenic mouse models of familial AD."	( Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet. Chen, X; Dasari, B; Geiger, JD; Ghribi, O; Larson, T; Marwarha, G; Prasanthi, JR, 2010)	2.52
"Caffeine ingestion has been associated with changes in FE(NO) concentration in adults."	( Changes to exhaled nitric oxide in asthmatic children after drinking a caffeine-containing cola drink. Abuzayan, I; Paraskavi, U; Turner, SW, 2010)	1.32
"Caffeine has been extensively used as a probe to measure CYP1A2 activity in humans with caffeine clearance or the paraxanthine (major metabolite of caffeine) to caffeine concentration ratio being regarded as the preferred metric. "	( Caffeine and paraxanthine HPLC assay for CYP1A2 phenotype assessment using saliva and plasma. Gross, AS; McLachlan, AJ; Perera, V, 2010)	3.25
"Caffeine intake has been suggested to be associated with the risk of hypertension. "	( Maternal caffeine intake, blood pressure, and the risk of hypertensive complications during pregnancy. The Generation R Study. Bakker, R; Hofman, A; Jaddoe, VW; Raat, H; Steegers, EA, 2011)	2.23
"Caffeine ingestion has been demonstrated to increase physical performance in some situations. "	( Acceleration tolerance after ingestion of a commercial energy drink. Balldin, U; Fischer, J; Storm, W; Walker, TB; Warren, GL, 2010)	1.8
"Caffeine has been shown to modulate cerebral blood flow, with little evidence of tolerance to these effects following habitual use. "	( Cerebral blood flow and behavioural effects of caffeine in habitual and non-habitual consumers of caffeine: a near infrared spectroscopy study. Haskell, CF; Kennedy, DO, 2011)	2.07
"Caffeine has been shown to affect both metabolism and sleep."	( Caffeine alters circadian rhythms and expression of disease and metabolic markers. Chapnik, N; Froy, O; Gutman, R; le Coutre, J; Meylan, J; Sherman, H, 2011)	2.53
"Caffeine has been shown to reduce leg-muscle pain during submaximal cycle ergometry, as well as in response to eccentric exercise. "	( Effect of caffeine intake on pain perception during high-intensity exercise. Astorino, TA; Burnett, TR; Roberson, DW; Terzi, MN, 2011)	2.21
"Caffeine intake has already been associated with high plasma levels of female hormones, but associations have not been clearly demonstrated in epidemiological studies."	( No association between coffee, tea or caffeine consumption and breast cancer risk in a prospective cohort study. Boutron-Ruault, MC; Clavel-Chapelon, F; Fagherazzi, G; Romieu, I; Touillaud, MS, 2011)	1.36
"Caffeine has been shown to be both an effective free radical scavenger and an intercalation inhibitor."	( Neocarzinostatin as a probe for DNA protection activity--molecular interaction with caffeine. Chao, PD; Chin, DH; Kuo, HM; Li, HH; Liu, CW, 2012)	1.32
"Caffeine users have been encouraged to consume caffeine regularly to maintain their caffeine tolerance and so avoid caffeine's acute pressor effects. "	( Habitual coffee and tea drinkers experienced increases in blood pressure after consuming low to moderate doses of caffeine; these increases were larger upright than in the supine posture. McMullen, MK; Shine, G; Towell, A; Whitehouse, JM, 2011)	2.02
"Caffeine has shown effectiveness for treating PDPH, decreasing the proportion of participants with PDPH persistence and those requiring supplementary interventions, when compared with placebo. "	( Drug therapy for treating post-dural puncture headache. Basurto Ona, X; Bonfill Cosp, X; Martínez García, L; Solà, I, 2011)	1.81
"Caffeine intake has been associated with a lower incidence of Alzheimer's disease (AD) in humans. "	( Caffeine induces beneficial changes in PKA signaling and JNK and ERK activities in the striatum and cortex of Alzheimer's transgenic mice. Arendash, GW; Burgess, S; Echeverria, V; Patel, S; Zeitlin, R, 2011)	3.25
"Caffeine has become the most prevalently consumed psychostimulant in the world, but its influences on daily real-world functioning are relatively unknown. "	( Caffeine enhances real-world language processing: evidence from a proofreading task. Brunyé, TT; Ditman, T; Mahoney, CR; Rapp, DN; Taylor, HA, 2012)	3.26
"Caffeine has desired stimulant effects similar to but weaker than both classical recreational drugs and novel psychoactive substances. "	( Risk of caffeine toxicity associated with the use of 'legal highs' (novel psychoactive substances). Dargan, PI; Davies, S; Lee, T; Ramsey, J; Wood, DM, 2012)	2.26
"Caffeine also has a potentially negative influence on bones."	( The influence of caffeine on the biomechanical properties of bone tissue during pregnancy in a population of rats. Chadaj-Polberg, E; Olchowik, G; Polberg, M; Tomaszewska, M; Tomaszewski, M, 2011)	1.43
"Caffeine has been used as a chemotherapy potentiator that inhibits DNA damage repair and enhances the cytocidal effects of anti-cancer drugs."	( Caffeine-potentiated chemotherapy for clear cell sarcoma: a report of five cases. Hayashi, K; Karita, M; Nishida, H; Shirai, T; Tsuchiya, H; Yamamoto, N, 2013)	2.55
"Caffeine has been reported to alter perceptions of exertion, muscle pain, and mood, yet the majority of existing data were obtained in resting volunteers or during steady-state exercise. "	( Effect of caffeine on RPE and perceptions of pain, arousal, and pleasure/displeasure during a cycling time trial in endurance trained and active men. Aburto-Pratt, K; Astorino, TA; Cottrell, T; Duhon, J; Talhami Lozano, A, 2012)	2.22
"Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and aspirin, in the belief that it enhances analgesic efficacy. "	( Caffeine as an analgesic adjuvant for acute pain in adults. Derry, CJ; Derry, S; Moore, RA, 2012)	3.26
"Caffeine has many diverse physiological effects including central nervous system stimulation. "	( Effect of caffeine on LT, VT and HRVT. Engels, HJ; Gretebeck, KA; Gretebeck, RJ; Karapetian, GK, 2012)	2.22
"Caffeine has been reported to enhance cognition in animal and humans. "	( Chronic caffeine treatment prevents stress-induced LTP impairment: the critical role of phosphorylated CaMKII and BDNF. Aleisa, AM; Alkadhi, KA; Alzoubi, KH; Srivareerat, M, 2013)	2.27
"Caffeine has been hypothesised as a thermogenic agent that might help to maintain a healthy body weight. "	( Caffeine dose-dependently induces thermogenesis but restores ATP in HepG2 cells in culture. Bytof, G; Hochkogler, CM; Lantz, I; Pignitter, M; Riedel, A; Rohm, B; Somoza, V; Walker, J, 2012)	3.26
"Caffeine has multiple actions, including inhibition of the DNA damage response, and its metabolites, 1-methylxanthine and 1-methyluric acid, are potent antioxidants."	( The methyl xanthine caffeine inhibits DNA damage signaling and reactive species and reduces atherosclerosis in ApoE(-/-) mice. Bennett, MR; Figg, N; Gray, K; Kumar, S; Mercer, JR, 2012)	1.42
"Caffeine consumption has been associated with a reduced risk of Parkinson's disease (PD). "	( Caffeine and risk of Parkinson's disease in a large cohort of men and women. Ascherio, A; Gao, X; Gapstur, S; McCullough, ML; Palacios, N; Schwarzschild, MA; Shah, R, 2012)	3.26
"Caffeine and melatonin have been shown to protect the Swedish mutant amyloid precursor protein (APP(sw)) transgenic mouse model of Alzheimer's disease from cognitive dysfunction. "	( Caffeine increases mitochondrial function and blocks melatonin signaling to mitochondria in Alzheimer's mice and cells. Arendash, GW; Bradshaw, PC; Cao, C; Copes, N; Delic, V; Dragicevic, N; Lin, X; Mamcarz, M; Wang, L, 2012)	3.26
"Caffeine has potent antioxidant properties."	( Caffeine's mechanisms of action and its cosmetic use. Herman, A; Herman, AP, 2013)	2.55
"Caffeine has been known to trigger seizures, however, the precise mechanism about the proconvulsive effect of caffeine remains unclear. "	( Caffeine-induced inhibition of the activity of glutamate transporter type 3 expressed in Xenopus oocytes. Do, SH; Kim, ST; Ryu, JH; Shin, HJ; Zuo, Z, 2013)	3.28
"Caffeine has been shown to increase preference for beverages with which it is paired; however, it is not known if caffeine alters liking for foods with which it is paired indirectly."	( Caffeine increases liking and consumption of novel-flavored yogurt. Bendlin, A; Panek, LM; Swoboda, C; Temple, JL, 2013)	3.28
"Caffeine has significant hemodynamic and humoral effects in habitual coffee drinkers that persist for many hours during the activities of everyday life. "	( Caffeine affects cardiovascular and neuroendocrine activation at work and home. Bryant, JE; Kuhn, CM; Lane, JD; Phillips-Bute, BG; Pieper, CF, )	3.02
"Caffeine has been detected in Boston Harbor seawater with concentrations ranging from 140 to 1600 ng l(-1), and in Massachusetts Bay seawater at concentrations from 5.2 to 71 ng l(-1). "	( Caffeine in Boston Harbor seawater. Chen, RF; Siegener, R, 2002)	3.2
"Caffeine has been imbibed since ancient times in tea and coffee, and more recently in colas. "	( Involvement of DARPP-32 phosphorylation in the stimulant action of caffeine. Bibb, JA; Fienberg, AA; Fisone, G; Fredholm, BB; Greengard, P; Kim, Y; Lindskog, M; Nairn, AC; Pozzi, L; Svenningsson, P, 2002)	1.99
"Caffeine has multiple pharmacological effects that influence normal physiological functioning, and it has been suspected of contributing to morbidity."	( A primer on caffeine pharmacology and its drug interactions in clinical psychopharmacology. DeVane, CL; Donovan, JL, 2001)	1.41
"Caffeine has previously been shown to activate CYP3A activity in vitro and to increase APAP hepatotoxicity in rodents pretreated with prototypic inducers of CYP3A."	( Effect of caffeine on acetaminophen hepatotoxicity in cultured hepatocytes treated with ethanol and isopentanol. Bement, J; Chatfield, K; DiPetrillo, K; Jeffery, E; Kostrubsky, V; Sinclair, J; Sinclair, P; Wood, S; Wrighton, S, 2002)	1.44
"Caffeine has been shown to reverse some of the performance-impairing effects of ethanol. "	( Caffeine reversal of ethanol effects on the multiple sleep latency test, memory, and psychomotor performance. Drake, CL; Roehrs, T; Roth, T; Scofield, HM; Turner, L, 2003)	3.2
"Caffeine has been reported to be an inhibitor of such repair processes."	( Detrimental effects of cryopreservation of loach (Misgurnus fossilis) sperm on subsequent embryo development are reversed by incubating fertilised eggs in caffeine. Holt, WV; Kopeika, E; Kopeika, J; Rawson, DM; Zhang, T, 2003)	1.24
"Caffeine has been shown to provide an accurate phenotypic probe for measuring CYP1A2 activity."	( Correlation of cytochrome P450 (CYP) 1A2 activity using caffeine phenotyping and olanzapine disposition in healthy volunteers. Hon, YY; Jann, MW; Lam, YW; Penzak, SR; Shirley, KL; Spratlin, V, 2003)	1.29
"Caffeine has shown an inhibitory role in invasion and proliferation in melanoma pulmonary metastasis as well as in high-grade tissue sarcoma. "	( Potentiation of lipid peroxidation in B16F10 and B16F1 melanoma cells by caffeine, a methylxanthine derivative: relationship to intracellular glutathione. Gude, RP; Shukla, V, 2003)	1.99
"Caffeine has been widely used to study ATM and ATR signaling because it inhibits these kinases in vitro and overcomes cell cycle checkpoint responses in vivo."	( Caffeine inhibits checkpoint responses without inhibiting the ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) protein kinases. Cortez, D, 2003)	2.48
"1. Caffeine has been widely used as a pharmacological tool to evaluate Ca(2+) release from the sarcoplasmic reticulum in isolated smooth muscle cells. "	( Acetylcholine and tachykinins involvement in the caffeine-induced biphasic change in intracellular Ca2+ in bovine airway smooth muscle. Arreola, JL; Barajas-López, C; Carbajal, V; Flores-Soto, E; Montaño, LM; Vargas, MH, 2003)	1.19
"Caffeine has been investigated for its potential mutagenic activity to bacteria, fungi and mammalian cells in culture, and at high concentrations it is also an inducer of apoptosis. "	( Apoptosis induced by different doses of caffeine on Chinese hamster ovary cells. Fernández, MJ; López, A; Santa-Maria, A, )	1.84
"Caffeine has been widely described as a chemo/radiosensitizing agent, presumably by inhibiting DNA repair, and affecting preferentially cells with an altered p53 status. "	( Conflicting effects of caffeine on apoptosis and clonogenic survival of human K1 thyroid carcinoma cell lines with different p53 status after exposure to cisplatin or UVc irradiation. Bergerat, JP; Céraline, J; Deplanque, G; Dufour, P; Klein-Soyer, C; Lapouge, G, 2004)	2.08
"1. Caffeine has wide-ranging activities on smooth muscles, including contractile and relaxant effects. "	( Effect of caffeine on response of rabbit isolated corpus cavernosum to high K+ solution, noradrenaline and transmural electrical stimulation. Adaikan, PG; Adebiyi, A, )	1.16
"Caffeine has been found in tissues of several plants. "	( Catabolism of caffeine in plants and microorganisms. Mazzafera, P, 2004)	2.13
"Caffeine has biphasic effects on locomotion, and blockade of the adenosine A(2A) receptor (A2AR) is necessary for the stimulatory effect of low doses of caffeine, but not for the locomotor depressant effect observed at high doses. "	( The adenosine A1 receptor contributes to the stimulatory, but not the inhibitory effect of caffeine on locomotion: a study in mice lacking adenosine A1 and/or A2A receptors. Adén, U; Dahlberg, V; Fredholm, BB; Halldner, L; Johansson, B; Ledent, C, 2004)	1.99
"Caffeine has been shown to increase the Ca(2+) release frequency (Ca(2+) sparks) from the sarcoplasmic reticulum (SR) through ryanodine-sensitive stores and relax gastric fundus smooth muscle. "	( CaM kinase II and phospholamban contribute to caffeine-induced relaxation of murine gastric fundus smooth muscle. Cho, SY; Han, IS; Kim, M; Koh, SD; Perrino, BA, 2005)	2.03
"Caffeine also has anti-thiamin properties and decaffeinated coffee was associated with a better clinical state than the caffeine containing version."	( Associations between diet and disease activity in ulcerative colitis patients using a novel method of data analysis. Cummings, JH; Curno, R; Edmond, LM; Kong, SC; Magee, EA; Tasker, SM, 2005)	1.05
"Caffeine has been shown to increase brain and plasma content of neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) that allosterically modulates GABA(A) receptors. "	( Reversal of caffeine-induced anxiety by neurosteroid 3-alpha-hydroxy-5-alpha-pregnane-20-one in rats. Chopde, CT; Hirani, K; Jain, NS, 2005)	2.15
"Caffeine ingestion has been associated with increased performance during endurance submaximal, and acute, high-intensity exercise."	( Caffeine: implications for alertness in athletes. Dinges, DF; Rogers, NL, 2005)	2.49
"Caffeine has reinforcing and anxiogenic properties. "	( Preference for caffeine appears earlier in non-anxious than in anxious mice. Costentin, J; Pelloux, Y; Vautrin, S, 2005)	2.12
"Caffeine has no effect on any of these end points in AT cells."	( Checkpoint abrogation in G2 compromises repair of chromosomal breaks in ataxia telangiectasia cells. Iliakis, G; Manola, KN; Pantelias, GE; Terzoudi, GI, 2005)	1.05
"Caffeine has been suggested as a possible risk factor for breast cancer, potentially through its effect of facilitating the development of benign breast disease. "	( Consumption of coffee, but not black tea, is associated with decreased risk of premenopausal breast cancer. Baker, JA; Beehler, GP; Jayaprakash, V; McCann, SE; Moysich, KB; Sawant, AC, 2006)	1.78
"Caffeine has also been reported to suppress human lymphocyte function as indicated by reduced T-cell proliferation and impaired production of Th1 (interleukin [IL]-2 and interferon [IFN]-gamma), Th2 (IL-4, IL-5) and Th3 (IL-10) cytokines."	( Immunomodulatory effects of caffeine: friend or foe? Connor, TJ; Horrigan, LA; Kelly, JP, 2006)	1.35
"Caffeine has been studied for its potential use as an ergogenic aid."	( Caffeine as an ergogenic aid. Armsey, TD; Keisler, BD, 2006)	2.5
"Caffeine also has effects on sleep."	( Effects of caffeine are more marked on daytime recovery sleep than on nocturnal sleep. Carrier, J; Dumont, M; Fernandez-Bolanos, M; Filipini, D; Paquet, J; Robillard, R; Selmaoui, B, 2007)	1.45
"Caffeine has long been recognized to influence post-replication repair, although the mechanism is not identified."	( Caffeine delays replication fork progression and enhances UV-induced homologous recombination in Chinese hamster cell lines. Erixon, K; Filippi, S; Helleday, T; Jenssen, D; Johansson, F; Lagerqvist, A; Palitti, F, 2006)	2.5
"Caffeine has induced FM1-43 internalization only in the presence of bivalent cations in the external solution."	( The role of extracellular calcium in exo- and endocytosis of synaptic vesicles at the frog motor nerve terminals. Abdrakhmanov, MM; Grigoryev, PN; Mukhamedyarov, MA; Zefirov, AL, 2006)	1.06
"Caffeine has marked effects on sleep, arousal and food intake. "	( Caffeine treatment regulates neuropeptide S system expression in the rat brain. Diéguez, C; Lage, R; López, M, 2006)	3.22
"Caffeine has intrinsic proarrhythmic effects; thus, its coadministration with an antiarrhythmic agent such as propafenone should be used with caution, especially in patients with poor CYP2D6 activity."	( Inhibitory effects of propafenone on the pharmacokinetics of caffeine in humans. Bélanger, PM; Ferron, LA; Gilbert, M; Grech-Bélanger, O; Labbé, L; Michaud, V; Mouksassi, MS; Turgeon, J, 2006)	1.3
"Caffeine has no flavor activity in soft-drinks yet will induce a physiologic and psychologic desire to consume the drink."	( Caffeine as a flavor additive in soft-drinks. Keast, RS; Riddell, LJ, 2007)	2.5
"Caffeine has been shown to improve sprint time, anaerobic power, and reaction time, all integral aspects of agility. "	( The effects of caffeine on athletic agility. Crixell, SH; Lloyd, LK; Lorino, AJ; Walker, JL, 2006)	2.13
"Caffeine has occasionally been considered a drug of abuse and the potential for dependence on caffeine has been debated."	( Clinical importance of caffeine dependence and abuse. Ogawa, N; Ueki, H, 2007)	1.37
"Caffeine has been suggested to act as a countermeasure against fatigue in military operations. "	( Effect of caffeine on simulator flight performance in sleep-deprived military pilot students. Huttunen, KH; Kilpeläinen, AA; Lahtinen, TM; Leino, TK; Lohi, JJ; Muhli, AA, 2007)	2.18
"Caffeine, which has a DNA-repair inhibiting effect, enhances the cytocidal effects of anticancer drugs and radiation. "	( Caffeine-potentiated chemotherapy for patients with high-grade soft tissue sarcoma: long-term clinical outcome. Hayashi, K; Kawahara, M; Miyamoto, K; Takeuchi, A; Tomita, K; Tsuchiya, H; Yamamoto, N; Yamauchi, K, )	3.02
"Caffeine has been shown to potentiate the toxicity of the EA alkaloids."	( Determination of caffeine and sympathomimetic alkaloids in weight loss supplements by high-performance liquid chromatography. Evans, RL; Siitonen, PH, 2008)	1.41
"Caffeine has been reported to prevent hepatocarcinogenesis. "	( Caffeine inhibits the proliferation of liver cancer cells and activates the MEK/ERK/EGFR signalling pathway. Matsumoto, K; Murawaki, Y; Nagahara, T; Okano, J, 2008)	3.23
"Only caffeine has substantial experimental backing for being ergogenic in exercise."	( Caffeine and other sympathomimetic stimulants: modes of action and effects on sports performance. Jones, G, 2008)	2.24
"Caffeine has beneficial effects on various aspects of athletic performance, but its effects on training have been neglected."	( Dose effect of caffeine on testosterone and cortisol responses to resistance exercise. Beaven, CM; Cronin, JB; Hansen, KT; Hopkins, WG; Lowe, TE; Wood, MR, 2008)	1.42
"Caffeine has some potential to benefit training outcomes via the anabolic effects of the increase in testosterone concentration, but this benefit might be counteracted by the opposing catabolic effects of the increase in cortisol and resultant decline in the testosterone:cortisol ratio."	( Dose effect of caffeine on testosterone and cortisol responses to resistance exercise. Beaven, CM; Cronin, JB; Hansen, KT; Hopkins, WG; Lowe, TE; Wood, MR, 2008)	2.14
"Caffeine (10 mM) has no effect on the binding of Ca, but releases a more labile fraction of Ca, which presumably accumulates in excess of the bound Ca."	( Effects of ATP on the interaction of Ca++, Mg++, and K+ with fragmented sarcoplasmic reticulum isolated from rabbit skeletal muscle. Carvalho, AP; Leo, B, 1967)	0.97
"Caffeine has been recommended for the treatment of apnea in newborn children. "	( Analysis of caffeine: comparison of the manual enzyme multiplied immunoassay (EMIT), automated EMIT, and high-performance liquid chromatography procedures. Aravind, MK; Ferrell, WJ; Miceli, JN, 1984)	2.09
"Thus caffeine consumption has been shown to significantly enhance the promoting phase but is without effect on the initiating phase of this carcinogenic process."	( Caffeine (1,3,7-trimethylxanthine), a temperature promoter of DMBA-induced rat mammary gland carcinogenesis. DeHoog, JV; Scieszka, KM; Senn, ER; Welsch, CW, 1983)	2.16
"Caffeine has similar actions when calcium overload is induced by increasing [Ca]0 or decreasing [Na]0."	( Caffeine actions on currents induced by calcium-overload in Purkinje fibers. Di Gennaro, M; Vassalle, M, 1984)	2.43
"Caffeine has several highly visible effects on mitosis in eggs of the sea urchin Strongylocentrotus purpuratus. "	( Caffeine-induced monaster cycling in fertilized eggs of the sea urchin Strongylocentrotus purpuratus. Harris, P, 1983)	3.15
"Caffeine has a multitude of pharmacologic actions and its effects must be determined on the fetus and newborn in the immediate future for suggestive evidence links caffeine with such fetal and newborn pathology as pre- and postmaturity and intrauterine growth retardation."	( Caffeine ingestion during pregnancy: in utero exposure and possible effects. Soyka, LF, 1981)	2.43
"Caffeine has been previously reported to enhance the lethal potential of many DNA-damaging agents in rodent cells1-5. "	( Effects of methylated xanthines on mammalian cells treated with bifunctional alkylating agents. Byfield, JE; Calabro-Jones, P; Murnane, JP; Ward, JF, 1980)	1.7
"Caffeine has been much used to examine the possibility that ryanodine receptors similar to those found in skeletal and cardiac muscle may be more widely distributed and perhaps contribute to regenerative Ca2+ signals in electrically inexcitable cells. "	( Caffeine-stimulated Ca2+ release from the intracellular stores of hepatocytes is not mediated by ryanodine receptors. McNulty, TJ; Taylor, CW, 1993)	3.17
"Caffeine has been used clinically to increase seizure length in electroconvulsive treatment (ECT). "	( Caffeine augmentation of electroconvulsive seizures. Fochtmann, L; Francis, A, 1994)	3.17
"Caffeine has been used as a metabolic probe to determine the relative levels of CYP1A2 activity in different individuals, since this compound is specifically 3-demethylated by CYP1A2. "	( Phenotyping of CYP1A2 in Japanese population by analysis of caffeine urinary metabolites: absence of mutation prescribing the phenotype in the CYP1A2 gene. Kadlubar, FF; Kamataki, T; Mizutani, M; Nakajima, M; Shin, S; Yokoi, T, )	1.82
"Caffeine has been shown to increase mean blood pressure, but studies documenting the effect of caffeine on digits are lacking. "	( The effect of caffeine on digital haemodynamics. Barton, B; Kleinert, JM, 1994)	2.09
"Caffeine has a biphasic effect on Ca(2+)-activated K+ current [IK(Ca)]: it induces a transient increase superimposed upon a sustained inhibition."	( Effects of caffeine on intracellular calcium, calcium current and calcium-dependent potassium current in anterior pituitary GH3 cells. Kramer, RH; Levitan, ES; Mokkapatti, R, 1994)	1.4
"Caffeine has induced no changes in the force-frequency relations of guinea-pig ventricular preparations."	( [Effect of caffeine on chronotropic correlations in the myocardium of the rat and guinea pig]. Karvatski?, IN; Shevchuk, VG; Shmygol, AV; Verkhratski?, AN, )	1.24
"Caffeine has rarely been reported as the cause of allergic reactions. "	( Urticaria induced by caffeine. Caballero, T; Diaz-Pena, JM; García-Ara, C; Ojeda, A; Pascual, C, )	1.89
"Caffeine has recently undergone scrutiny as a co-morbid risk factor with other substance dependencies, and in other medical and psychiatric conditions."	( Primary caffeine dependence: a case report. Adams, D; Ditzler, T; Haning, WF, 1993)	1.44
"Caffeine has been found to test similar to antidepressant drugs on at least one other behavioral screen, but caffeine does not possess clinical antidepressant properties."	( Effects of caffeine and PD 116,600 on the differential-reinforcement-of-low rate 72-S (DRL 72-S) schedule of reinforcement. Heffner, TG; Li, AA; Marek, GJ; Richards, JB; Seiden, LS; Shaughnessy, RA, 1993)	1.4
"Caffeine has also been reported to retard meiotic progression and induce aneuploidy in hamster oocytes in vitro."	( Cytogenetic effects of caffeine during in vivo mouse oocyte maturation. London, SN; Mailhes, JB; Young, D, 1996)	1.33
"Caffeine has been found to enhance endurance performance, while creatine and bicarbonate loading were generally found to benefit short term strenuous exercise."	( Nutrition for improved sports performance. Current issues on ergogenic aids. Clarkson, PM, 1996)	1.02
"Caffeine intake has been associated with risk of osteoporosis, breast cancer, endometriosis, and fibrocystic breast disease and has been hypothesized to exert its effects through alteration of endogenous hormone levels. "	( Caffeine intake and endogenous sex steroid levels in postmenopausal women. The Rancho Bernardo Study. Barrett-Connor, E; Ferrini, RL, 1996)	3.18
"1. Caffeine has been used to determine acetylator phenotype for some 15 years but the interpretation of metabolic ratios with this substance raises theoretical and methodological issues. "	( Caffeine as a metabolic probe: NAT2 phenotyping. Bennett, PN; Dobrocky, P; Godlewski, G; Jones, RW; Notarianni, LJ, 1996)	2.36
"Caffeine has a more pronounced effect on phase 2A (16-36 min) than on phase 2, with significant effects being observed at lower doses."	( Caffeine antinociception: role of formalin concentration and adenosine A1 and A2 receptors. Reid, A; Sawynok, J, 1996)	2.46
"Caffeine ingestion has been demonstrated to increase circulating epinephrine (Epi) and norepinephrine (NE), elevate free fatty acids (FFAs), and alter heart rate, blood pressure (BP), and ventilation in humans. "	( Acute effects of caffeine ingestion at rest in humans with impaired epinephrine responses. Graham, TE; Kjaer, M; Mohr, T; Van Soeren, M, 1996)	2.08
"Caffeine restriction has no role in the management of patients referred with symptomatic idiopathic ventricular premature beats."	( Caffeine restriction has no role in the management of patients with symptomatic idiopathic ventricular premature beats. Boon, NA; Jarvie, DR; Neilson, JM; Newby, DE, 1996)	3.18
"Caffeine has been extensively used to study intracellular Ca2+ control and contraction-relaxation in cardiomyocytes. "	( Caffeine decreases intracellular free Mg2+ in isolated adult rat ventricular myocytes. Li, HY; Quamme, GA, 1997)	3.18
"Caffeine has been chosen to study this influence because as itself and its metabolites, it allows the preparation of different methylxanthine isotopomers and thus is one of the best models to study isotopic effects induced by stable isotope labelling."	( Isotopic effects on retention times of caffeine and its metabolites 1,3,7-trimethyluric acid, theophylline, theobromine and paraxanthine. Benchekroun, Y; Brazier, JL; Dautraix, S; Désage, M, 1997)	1.29
"Caffeine has been shown to bypass the G2/M-phase checkpoint in mammalian cells and in cycling Xenopus extracts and to induce mitosis despite the presence of damaged or unreplicated DNA."	( Caffeine overrides the S-phase cell cycle block in sea urchin embryos. Patel, R; Whitaker, M; Wright, EM, 1997)	2.46
"Caffeine has no adjuvant analgesic effect."	( Do codeine and caffeine enhance the analgesic effect of aspirin?--A systematic overview. Po, AL; Zhang, WY, 1997)	1.37
"Caffeine intake has been proposed to influence breast cancer risk. "	( Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese women. Kabuto, M; Nagata, C; Shimizu, H, 1998)	2.01
"Caffeine intake has been associated with fetal harm and now SIDS. "	( Heavy caffeine intake in pregnancy and sudden infant death syndrome. New Zealand Cot Death Study Group. Ford, RP; Mitchell, EA; Schluter, PJ; Scragg, R; Stewart, AW; Taylor, BJ, 1998)	2.22
"Caffeine has an ergogenic effect on endurance performance in dosages of 3 to 6 mg/kg."	( [The use of drugs to improve athletic performance]. Hartgens, F; Kuipers, H, 1997)	1.02
"Caffeine has a DNA-repair inhibiting effect."	( Caffeine-assisted chemotherapy and minimized tumor excision for nonmetastatic osteosarcoma. Asada, N; Kitano, S; Mori, Y; Morinaga, T; Tomita, K; Tsuchiya, H; Yamamoto, N, )	2.3
"Caffeine has both positive effects that contribute to widespread consumption of caffeine-containing beverages and adverse unpleasant effects if doses are increased. "	( Caffeine--an atypical drug of dependence. Daly, JW; Fredholm, BB, )	3.02
"Caffeine has been reported to induce contralateral rotational behaviour in rats bearing a unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal pathway. "	( Motor stimulant effects of caffeine in 6-hydroxydopamine-lesioned rats are dependent on previous stimulation of dopamine receptors: a different role of D1 and D2 receptors. Fenu, S; Morelli, M, 1998)	2.04
"Caffeine has been known for some time to have the capacity to override the S-M checkpoint in animal cells."	( Caffeine can override the S-M checkpoint in fission yeast. Harris, AL; Norbury, C; Toda, T; Wang, SW, 1999)	2.47
"Caffeine clearance has traditionally been reported as either an absolute value or as directly proportional to body weight."	( Caffeine overdose in a premature infant: clinical course and pharmacokinetics. Anderson, BJ; Gunn, TR; Holford, NH; Johnson, R, 1999)	2.47
"Caffeine consumption has been implicated in the development of cardiovascular disease. "	( Effects of caffeine on heart mitochondria in newborn rats. Joseph, F; Nakamoto, T; Rossowska, MJ; Wink, CS; Yazdani, M, 1999)	2.14
"Caffeine has been found to inhibit the formation and action of Ca2+-mobilizing inositol 1,4,5-trisphosphate (IP3) in pancreatic acinar cells. "	( Caffeine inhibits a low affinity but not a high affinity mechanism for cholecystokinin-evoked Ca2+ signalling and amylase release from guinea pig pancreatic acini. Gylfe, E; Sjödin, L, 2000)	3.19
"Caffeine consumption has been proposed as a risk factor for bone loss in postmenopausal women. "	( Bone status among postmenopausal women with different habitual caffeine intakes: a longitudinal investigation. Cusatis, DC; Eggli, DF; Johnson-Rollings, N; Kieselhorst, K; Lloyd, T; Mauger, EA, 2000)	1.99
"Caffeine has a variety of pharmacological effects. "	( Caffeine for asthma. Bara, AI; Barley, EA, 2000)	3.19
"Caffeine has for many years been known to be involved in the sensitization of DNA to damage. "	( Caffeine does not cause override of the G2/M block induced by UVc or gamma radiation in normal human skin fibroblasts. Bergerat, JP; Cazenave, JP; Deplanque, G; Klein-Soyer, C; Mah-Becherel, MC; Vincent, F, 2000)	3.19
"Caffeine, which has a DNA-repair inhibiting effect, enhances the cytocidal effects of anticancer drugs and radiation. "	( Caffeine-potentiated radiochemotherapy and function-saving surgery for high-grade soft tissue sarcoma. Asada, N; Kanazawa, Y; Nishijima, H; Takanaka, T; Terasaki, T; Tomita, K; Tsuchiya, H; Yamamoto, N, )	3.02
"Caffeine has been found to occur as a fungal metabolite and to be the principal alkaloid in sclerotia of Claviceps sorghicola, a Japanese ergot pathogen of Sorghum spp."	( Caffeine: also a fungal metabolite. Bogo, A; Mantle, PG, 2000)	3.19
"Caffeine has a synergistic effectiveness with analgesics. "	( Do caffeine-containing analgesics promote dependence? A review and evaluation. Dalessio, D; Feinstein, AR; Fox, JM; Goldstein, J; Haag, G; Heinemann, LA; Ladewig, D; O'Brien, CP, 2000)	2.37
"Caffeine has been used as a pharmacological tool to study the ryanodine receptor (RYR)-mediated Ca2+ release from caffeine-sensitive, inositol 1,4,5,-trisphosphate (IP3)-insensitive pools. "	( Multiple effects of caffeine on Ca2+ release and influx in human B lymphocytes. Daly, JW; Gallagher, KL; Sei, Y, 2001)	2.08
"Caffeine reinforcement has been demonstrated in about 45% of normal subjects with histories of moderate and heavy caffeine use."	( Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement. Chausmer, AL; Griffiths, RR, 2000)	2.47
"Caffeine has potential properties to counteract the central effects of morphine."	( Effects of caffeine as an adjuvant to morphine in advanced cancer patients. A randomized, double-blind, placebo-controlled, crossover study. Casuccio, A; Mercadante, S; Serretta, R, 2001)	1.42
"Caffeine has been shown to react with the radiation-derived oxidants."	( Mechanism of protection against radiation-induced DNA damage in plasmid pBR322 by caffeine. Devasagayam, TP; Jayashree, B; Kesavan, PC; Kumar, SS, 2001)	1.26
"Caffeine has been used frequently in the treatment and prevention of apnea of prematurity. "	( Caffeine metabolism in premature infants. al-Alaiyan, S; al-Rawithi, S; el-Yazigi, A; Legayada, E; Raines, D; Shoukri, MM; Yusuf, A, 2001)	3.2
"Caffeine has been associated with a number of negative effects and addiction."	( The best defense against hypoglycemia is to recognize it: is caffeine useful? Kerr, D; Watson, J, 1999)	1.27
"Caffeine has been known to stimulate lipolysis that spares stored glycogen utilization during moderate intensity exercise."	( Caffeine as a lipolytic food component increases endurance performance in rats and athletes. Cha, YS; Choi, SK; Joung, SS; Lee, S; Lim, K; Ryu, S; Suh, H, 2001)	2.47
"Caffeine has known ergogenic effects, some of which have been observed during submaximal isometric contractions. "	( Caffeine increases endurance and attenuates force sensation during submaximal isometric contractions. Cafarelli, E; Plaskett, CJ, 2001)	3.2
"Caffeine has a variety of pharmacological effects. "	( Caffeine for asthma. Bara, AI; Barley, EA, 2001)	3.2
"Caffeine, which has a wide range between therapeutic and toxic levels, is a widely used medication for prevention and treatment of apnoea of prematurity. "	( Caffeine intoxication in a premature neonate. Aksoy, E; Atalay, Y; Dalgiç, N; Ergenekon, E; Koç, E, 2001)	3.2
"Caffeine has the potential to be used as a contrast booster for fMRI experiments."	( On the use of caffeine as a contrast booster for BOLD fMRI studies. Gitelman, DR; Mesulam, MM; Mulderink, TA; Parrish, TB, 2002)	1.4
"Caffeine has been an additive in analgesics for many years. "	( A benefit-risk assessment of caffeine as an analgesic adjuvant. Zhang, WY, 2001)	2.04
"Caffeine citrate has many advantages over theophylline, however, including once-a-day dosing, more predictable plasma concentrations, earlier onset of action, and minimal side effects."	( Theophylline or caffeine: which is best for apnea of prematurity? Gannon, BA, 2000)	1.37
"Caffeine has no effect on mutagenesis by nitrous acid or ethyl methanesulfonate; it depresses UV mutagenesis, but only at 37 C and at high UV dosages."	( Effects of growth temperature and caffeine on genetic responses of Candida albicans to ethyl methanesulfonate, nitrous acid and ultraviolet radiation. Bish, JT; Sarachek, A, 1976)	1.26
"Caffeine has potent mutagenic effects in Escherichia coli and other micro-organisms both when acting alone and in combination with other mutagens."	( Caffeine. Timson, J, 1977)	2.42
"The caffeine, which has no effect on hnRNA size in control cells, inhibits to a considerable extent the restoration of full-length transcripts during postirradiation incubation."	( Effects of ultraviolet irradiation and postirradiation incubation on heterogenous nuclear RNA size in murine cells. Ali, R; Sauerbier, W, 1978)	0.74
"Caffeine has been found to potentiate the acute anti-inflammatory activity of aspirin, indomethacin, and phenylbutazone, but not the activity of sodium salicylate or hydrocortisone, in the carrageenan pleurisy or hindlimb models of inflammation in the rat. "	( Potentiation of the anti-inflammatory and analgesic activity of aspirin by caffeine in the rat. Ellis, CH; Selph, JL; Truax, JF; Vinegar, R; Welch, RM; White, HL, 1976)	1.93
"Caffeine, which has been observed to inhibit some DNA-repair processes in intact cells, had no effect on DNA polymerase activities from XP-A, XP-C, XP-D or XP-variant cells."	( Levels of DNA polymerases alpha, beta, and gamma in control and repair-deficient human diploid fibroblasts 1. Lieberman, MW; Parker, VP, 1977)	0.98
"Caffeine has also been shown to undergo 3-demethylation by CYP1A2, and it is further acetylated to 5-acetylamino-6-formylamino-3-methyluracil (AFMU) by the polymorphic NAT2."	( Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Butler, MA; Caporaso, NE; Hayes, RB; Kadlubar, FF; Lang, NP; Lawsen, MF; Massengill, JP; Teitel, CH; Vineis, P; Young, JF, 1992)	1.23
"Caffeine has been known to enhance lethal and chromosome damaging effects of chemical and physical mutagens. "	( A possible involvement of DNA topoisomerase I in "caffeine effect" after ultraviolet irradiation. Oikawa, A; Tohda, H; Zhao, JH, 1992)	1.98
"Caffeine has been found by different authors to considerably enhance the expression of chromosome breaks which have been produced by other agents."	( The effect of caffeine on DAPI-inducible fragile sites. Pelliccia, F; Rocchi, A, 1992)	1.37
"Caffeine has the advantage of being well tolerated when administered orally; the saliva level parallels the serum concentration, making a non-invasive test feasible."	( New methods for assessing liver function in infants and children. A-Kader, HH; Balistreri, WF; Gremse, D; Ryckman, FC; Schroeder, TJ; Setchell, KD, )	0.85
"Caffeine has been reported to have a positive and (or) a negative inotropic effect on cardiac muscle. "	( Rat atrial muscle responses with caffeine: dose-response, force frequency, and postrest contractions. Harms, R; Lobo, J; MacIntosh, BR; Posner, P, 1992)	2.01
"Caffeine thus has limited dependence potential."	( Stimulus functions of caffeine in humans: relation to dependence potential. Heishman, SJ; Henningfield, JE, 1992)	1.32
"High caffeine consumption has been proposed as a risk factor for osteoporotic fracture, but the evidence associating high caffeine intake with low bone density is inconsistent. "	( Is caffeine consumption a risk factor for osteoporosis? Atkinson, EJ; Cooper, C; Judd, HL; Melton, LJ; O'Fallon, WM; Riggs, BL; Wahner, HW, 1992)	1.42
"Caffeine has previously been shown to diminish or potentiate acetaminophen (APAP) hepatotoxicity in rats, depending on induction state. "	( Inhibition and activation of acetaminophen reactive metabolite formation by caffeine. Roles of cytochromes P-450IA1 and IIIA2. Kalhorn, TF; Lee, CA; Nelson, SD; Slattery, JT; Thummel, KE, )	1.8
"Caffeine has recently been used to test liver function, but the effect of diabetes on caffeine kinetics is not known."	( Pharmacokinetics of caffeine in patients with decompensated type I and type II diabetes mellitus. Wietholtz, H; Zysset, T, 1991)	1.33
"Caffeine has been associated with a number of reproductive and developmental effects in animals and humans. "	( Somatic development of the infant monkey following in utero exposure to caffeine. Gilbert, SG; Rice, DC, 1991)	1.96
"Caffeine has a wide range of behaviorally active properties. "	( Caffeine effects on behavioral thermoregulation. McNeil, MJ; Quinn, JM; Rust, ML; Vitulli, WF, 1991)	3.17
"Caffeine has been shown to affect both physiological functioning and certain aspects of performance. "	( Caffeine and novelty: effects on electrodermal activity and performance. Davidson, RA; Smith, BD, 1991)	3.17
"Caffeine, which has anxiogenic effects in man, produces effects in rats which are similar to those of rCRF."	( Central effects of corticotropin releasing factor (CRF): evidence for similar interactions with environmental novelty and with caffeine. Britton, DR; Indyk, E, 1990)	1.21
"4) Caffeine consumption has an association with alcohol use and smoking habit among males."	( Caffeine consumption among medical students. Fujimura, T; Mino, Y; Ohara, H; Yasuda, N, 1990)	2.24
"Caffeine has been reported to induce S-phase condensation in cells where replication is arrested, by accelerating cell cycle progression as well as by uncoupling it from replication; for, in BHK or CHO hamster cells arrested in early S-phase and given caffeine, condensed chromosomes appear well before the normal time at which mitosis occurs in cells released from arrest."	( Caffeine overcomes a restriction point associated with DNA replication, but does not accelerate mitosis. Downes, CS; Johnson, RT; Musk, SR; Watson, JV, 1990)	2.44
"Caffeine has greater affinity for slow SR, whereas doxorubicin, ruthenium red, and ryanodine have greater affinity for fast SR."	( Ca2+ release from sarcoplasmic reticulum of skinned fast- and slow-twitch muscle fibers. Salviati, G; Volpe, P, 1988)	1
"Thus caffeine has no effect on gamma even though it produces a dose-related increase in locomotions."	( Another look at amphetamine-induced stereotyped locomotor activity in rats using a new statistic to measure locomotor stereotypy. Cross, DR; Hollingsworth, EM; Mueller, K, 1989)	0.73
"Caffeine has been reported to enhance performance by increasing fat utilization and by sparing liver and muscle glycogen. "	( Effect of intravenous caffeine on muscle glycogenolysis in fasted exercising rats. Arogyasami, J; Winder, WW; Yang, HT, 1989)	2.03
"As caffeine has been shown to selectively increase dopaminergic neurotransmission in mesocortical neurons, further study utilizing dopamine agonists during SPEM in schizophrenic patients is warranted."	( Smooth pursuit eye movements in schizophrenia: effects of neuroleptic treatment and caffeine. Clem, T; Hommer, DW; Litman, RE; Pato, CN; Pickar, D; Rapaport, MH, 1989)	1.02
"Caffeine has long been recognized as an addictive substance with numerous toxic effects. "	( Massive caffeine ingestion resulting in death. Dean, BS; Krenzelok, EP; Mrvos, RM; Reilly, PE, 1989)	2.15
"Caffeine has been reported to enhance performance by increasing lipid oxidation and sparing liver and muscle glycogen in human subjects during prolonged endurance exercise. "	( Effect of caffeine on glycogenolysis during exercise in endurance trained rats. Arogyasami, J; Winder, WW; Yang, HT, 1989)	2.12
"Caffeine has been reported to induce premature chromosome condensation (PCC) in S-phase cells in the presence of an inhibitor of DNA synthesis. "	( X-ray-related potentially lethal damage expressed by chromosome condensation and the influence of caffeine. Nishimoto, T; Sasaki, H, 1989)	1.94
"Caffeine has been reported to enhance the expression of the fragile X [fra(X)] and common fragile sites in peripheral blood lymphocyte cultures (PBLC) treated with 5-fluorodeoxyuridine (FUdR). "	( The effect of caffeine on fragile X expression. Abruzzo, MA; Jacobs, PA; Mayer, M; Pettay, D, 1986)	2.07
"Caffeine has no effect on aspartame, sucrose, fructose, and calcium cyclamate."	( Caffeine intensifies taste of certain sweeteners: role of adenosine receptor. Beeker, TG; Diaz, C; Schiffman, SS, 1986)	2.44
"Caffeine has the opposite effect of adenosine and is the antagonist at the inhibitory A1-receptor."	( Caffeine: a new look at an age-old drug. Gupta, P; Somani, SM, 1988)	2.44
"Caffeine has been cited as a risk factor for osteoporosis in humans. "	( The effect of chronic caffeine administration on serum markers of bone mineral metabolism and bone histomorphometry in the rat. Epstein, S; Fallon, M; Glajchen, N; Ismail, F; Jowell, PS, 1988)	2.03
"Caffeine clearance has been determined in 117 volunteers and patients (including 27 patients with liver cirrhosis) after oral application of 366.1 mg caffeine according to conventional pharmacokinetic methods (Cl = D/AUC). "	( [One point determination of oral caffeine clearance in patients with liver diseases]. Brachtel, D; Epping, J; Hofstetter, G; Joeres, R; Junggeburth, J; Klinker, H; Richter, E; Zilly, W, 1988)	2
"Caffeine also has an inhibitory effect which is partly attributable to decrease in [Ca2+]cyt and partly to the decrease in the sensitivity to Ca2+ of the contractile elements."	( Multiple effects of caffeine on contraction and cytosolic free Ca2+ levels in vascular smooth muscle of rat aorta. Karaki, H; Ozaki, H; Sato, K, 1988)	1.32
"Caffeine has been reported to induce similar premature chromosome condensation in cells arrested with DNA polymerase inhibitors; this is the first recognition that such events occur in response to caffeine treatment after DNA damage."	( Caffeine induces uncoordinated expression of cell cycle functions after ultraviolet irradiation. Accelerated cycle transit, sister chromatid exchanges and premature chromosome condensation in a transformed Indian muntjac cell line. Downes, CS; Johnson, RT; Musk, SR, 1988)	2.44
"Caffeine has previously been demonstrated to be teratogenic in mice, causing primarily limb reduction defects and cleft palate. "	( Interactions between caffeine and adenosine agonists in producing embryo resorptions and malformations in mice. Clark, RL; Cusick, WA; Eschbach, K; Heyse, JF, 1987)	2.03
"Caffeine has been proposed as a marker for drug acetylation on the basis of a ratio of urinary metabolites (5-acetylamino-6-formylamino-3-methyl uracil and 1-methylxanthine, AFMU:MX) determined by high-performance liquid chromatography."	( Caffeine as a potential indicator for acetylator status. Fell, AF; Hudson, SA; Rankin, RB, 1987)	2.44
"Caffeine has been reported to result in bronchodilation in asthmatic children. "	( The bronchodilator effect of caffeine in adult asthmatics. Bukowskyj, M; Nakatsu, K, 1987)	2.01
"Caffeine has previously been shown to significantly improve certain aspects of human performance, particularly sustained vigilance, when administered in low and moderate doses (32 to 256 mg)."	( The effects of caffeine and aspirin on mood and performance. Coviella, IL; Emde, GG; Lieberman, HR; Wurtman, RJ, 1987)	1.35
"Caffeine, which has been linked to benign breast disease, has an antineoplastic effect in experimental animals, whereas in tissue cultures it inhibits mitoses and induces cell differentiation. "	( Association of tumor differentiation with caffeine and coffee intake in women with breast cancer. Aufses, AH; Fagerstrom, R; Feinberg, M; Papatestas, AE; Pozner, J; Saevitz, J; Schwartz, I, 1986)	1.98
"Caffeine has been found to alter the behavior of ADD children in a manner resembling more widely prescribed stimulant medications."	( Will population decreases in caffeine consumption unveil attention deficit disorders in adults? Dalby, JT, 1985)	1.28
"Caffeine has a similar overall effect in control and A-T cell lines in reducing the G2 arrest observed after ionizing radiation."	( Effect of caffeine on gamma-ray-induced G2 delay in ataxia telangiectasia. Bates, PR; Imray, FP; Lavin, MF, 1985)	1.39
"Caffeine, which has an effective partition coefficient that approaches that of thiopental, was used as an indicator substance to estimate the immediate volume of distribution of thiopental."	( Correlation between thiopental induction dose and the volume of distribution of caffeine in human subjects. Bizzarri, DV; DeLaRocha, A; Inchiosa, MA; Milliken, RA; Schmahai, TJ, 1986)	1.22
"Caffeine has been shown to enhance the lethal effect of DNA-damaging agents in mammalian cells, and the potentiation by caffeine of this effect is generally interpreted as the result of inhibition by caffeine of the repair of damaged DNA. "	( Caffeine alone causes DNA damage in Chinese hamster ovary cells. Ishida, R; Kozaki, M; Takahashi, T, 1985)	3.15

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Caffeine can cause anxiety symptoms in normal individuals, especially in vulnerable patients, like those with pre-existing anxiety disorders. Caffeine could enhance the anti-tumor effect of cisplatin in rat osteosarcoma.

Excerpt	Reference	Relevance
"Caffeine promotes IFN-γ production in Th1 cells from RA patients in vitro by competitive inhibition of adenosine receptor A2a. "	( Adenosine receptor A2a blockade by caffeine increases IFN-gamma production in Th1 cells from patients with rheumatoid arthritis. Breuninger, M; Gloyer, L; Golumba-Nagy, V; Jochimsen, D; Kofler, DM; Meyer, A; Schiller, J; Yan, S, 2022)	2.44
"Caffeine was found to enhance measures of sign-tracking behavior in Sprague-Dawley rats in a sign/goal-tracking procedure."	( Acute caffeine enhances sign-tracking in male Sprague-Dawley rats. Barun Shrestha, R; Carroll, KL; Holden, JM; Miller, C; Ng, ZT; Salem, A; Tibbetts, M, 2022)	1.92
"Caffeine could enhance the effectiveness of an existing drug for CRC treatment despite having little impact on the cell survival rate of CRC cells. "	( Caffeine enhances chemosensitivity to irinotecan in the treatment of colorectal cancer. Kim, KP; Lee, BK; Yoon, S, 2023)	3.8
"Caffeine poisoning may cause life-threatening arrhythmias and hemodynamic failure. "	( Massive suicidal ingestion of caffeine: a case report with investigation of the cardiovascular effect/concentration relationships. Chevillard, L; Grémain, V; Mégarbane, B; Saussereau, E; Schnell, G, 2021)	2.35
"Caffeine promotes memory consolidation. "	( Caffeine Increases Hippocampal Sharp Waves in Vitro. Ikegaya, Y; Watanabe, Y, 2017)	3.34
"Caffeine did not produce an effect."	( Transcranial direct current stimulation versus caffeine as a fatigue countermeasure. Goodyear, C; McIntire, LK; McKinley, RA; Nelson, JM, )	1.11
"Caffeine can increase seizure susceptibility and protect from seizures, depending on the dose, administration type (chronic or acute), and the developmental stage at which caffeine exposure started."	( Caffeine and seizures: A systematic review and quantitative analysis. Bauer, PR; Sander, JW; Schuitema, I; van Koert, RR; Visser, GH, 2018)	2.64
"Caffeine at lower (micromolar) and relatively non-toxic concentrations has been shown to promote anti-tumor immune response (A2 A) and to inhibit tumor angiogenesis (A3) and migration (A2B) by antagonizing adenosine receptors."	( Mechanistic considerations in chemotherapeutic activity of caffeine. Nayak, PK; Tej, GNVC, 2018)	1.45
"Caffeine does not increase respiration in p27-deficient animals, whereas aged mice display improvement after 10 days of caffeine in drinking water."	( CDKN1B/p27 is localized in mitochondria and improves respiration-dependent processes in the cardiovascular system-New mode of action for caffeine. Abrams, M; Ale-Agha, N; Altschmied, J; Aufenvenne, K; Deenen, R; Dyballa-Rukes, N; Eckermann, O; Fischer, JW; Gonnissen, S; Gorressen, S; Goy, C; Grandoch, M; Haendeler, J; Jakob, S; Jakobs, P; Köhrer, K; Spannbrucker, T; Spyridopoulos, I; Unfried, K; von Ameln, F; Zurek, M, 2018)	1.4
"Caffeine can also produce negative allelopathic effects that prevent the growth of surrounding plants."	( Caffeine Extraction, Enzymatic Activity and Gene Expression of Caffeine Synthase from Plant Cell Suspensions. Hernández-Sotomayor, SMT; Monforte-González, M; Muñoz-Sánchez, JA; Pech-Kú, R; Rodas-Junco, BA; Vázquez-Flota, F, 2018)	2.64
"Caffeine induced an increase in the intracellular Ca(2+) concentration and ROS generation leading to p38 MAPK activation and ERK inactivation, respectively."	( Cross talk between p38MAPK and ERK is mediated through MAPK-mediated protein phosphatase 2A catalytic subunit α and MAPK phosphatase-1 expression in human leukemia U937 cells. Chang, LS; Chen, YJ; Cheng, TL; Lin, SR; Liu, WH, 2013)	1.11
"Caffeine could activate the HERV-W env promoter, while aspirin could not."	( Activation of elements in HERV-W family by caffeine and aspirin. Chen, Y; Li, S; Liu, C; Wang, X; Yu, H; Zeng, J; Zhu, F, 2013)	1.37
"Caffeine is assumed to increase tHcy levels by acting as a vitamin B6 antagonist."	( Relationship between plasma total homocysteine level and dietary caffeine and vitamin B6 intakes in pregnant women. Haruna, M; Matsuzaki, M; Murashima, S; Murayama, R; Ota, E; Sasaki, S; Shiraishi, M; Yeo, S, 2014)	1.36
"Caffeine displays significant antioxidant ability in protecting membranes against oxidative damage and can lower the risk of insulin resistance."	( Caffeine intake improves fructose-induced hypertension and insulin resistance by enhancing central insulin signaling. Chen, BR; Cheng, PW; Cheng, WH; Ho, WY; Liou, JC; Liu, CP; Lu, PJ; Sun, GC; Tseng, CJ; Yeh, TC, 2014)	2.57
"Caffeine displays a broad array of actions on the brain."	( Effects of caffeine on neuronal apoptosis in neonatal hypoxic-ischemic brain injury. Daglioglu, YK; Erdogan, S; Kilicdag, H; Zorludemir, S, 2014)	1.51
"Caffeine promotes wakefulness during night shift work, although it also disturbs subsequent daytime sleep. "	( Effects of caffeine on skin and core temperatures, alertness, and recovery sleep during circadian misalignment. McHill, AW; Smith, BJ; Wright, KP, 2014)	2.23
"Caffeine seems to enhance exercise tolerance through improved performance with no subsequent increase in fatigue or perception of exertion and may be an appropriate strategy to promote exercise participation in prostate cancer survivors."	( Effect of caffeine on exercise capacity and function in prostate cancer survivors. Bolam, KA; Cornish, RS; Skinner, TL, 2015)	1.54
"Caffeine promotes anti-inflammatory effects in the immature lung of prenatal LPS-exposed rat pups associated with improvement of Rrs, suggesting a protective effect of caffeine on respiratory function via an anti-inflammatory mechanism."	( Anti-inflammatory effect of caffeine is associated with improved lung function after lipopolysaccharide-induced amnionitis. Balan, KV; Jafri, A; Kc, P; Köroğlu, OA; MacFarlane, PM; Martin, RJ; Zenebe, WJ, 2014)	2.14
"Caffeine is used to increase the sensitivity of RyRs to cytosolic Ca(2+) concentration ([Ca(2+)]i) and sarcoplasmic reticulum Ca(2+) ([Ca(2+)]SR)."	( Ryanodine receptor sensitization results in abnormal calcium signaling in airway smooth muscle cells. Brook, BS; Chen, J; Croisier, H; Sanderson, MJ; Sneyd, J; Tan, X, 2015)	1.14
"Caffeine seems to enhance short-duration exercise performance in P."	( Ergogenic Effects of Caffeine Consumption in a 3-min All-Out Arm Crank Test in Paraplegic and Tetraplegic Compared With Able-Bodied Individuals. Flueck, JL; Krebs, J; Liener, M; Perret, C; Schaufelberger, F, 2015)	1.46
"Caffeine may inhibit IR-related apoptosis of bladder cancer RT4 cells by suppressing activation of the ATM-Chk2-p53-Puma axis."	( Caffeine Suppresses Apoptosis of Bladder Cancer RT4 Cells in Response to Ionizing Radiation by Inhibiting Ataxia Telangiectasia Mutated-Chk2-p53 Axis. Chen, JM; Luo, W; Wang, BH; Xiao, J; Zhang, ZW, 2015)	3.3
"Caffeine is able to increase the effect of rac-Flur in the arthritic gout-type pain in rats."	( Antinociceptive Effect of Racemic Flurbiprofen and Caffeine Co-Administration in an Arthritic Gout-Type Pain in Rats. Espinosa-Juárez, JV; Jaramillo-Morales, OA; Liévano-Reyes, R; López-Muñoz, FJ; Pérez-Méndez, HI; Solís-Oba, A, 2016)	1.41
"Caffeine did not increase the number of self-administered drinks."	( Effects of caffeine on alcohol reinforcement: beverage choice, self-administration, and subjective ratings. Evatt, DP; Griffiths, RR; Meredith, SE; Sweeney, MM, 2017)	1.57
"Caffeine may inhibit repair of DNA lesions through a direct interference with DNA-PK activity and other repair enzymes."	( Modulation of cellular response to anticancer treatment by caffeine: inhibition of cell cycle checkpoints, DNA repair and more. Sabisz, M; Skladanowski, A, 2008)	1.31
"Caffeine overdoses produce multiple symptoms, most of which are commonly associated with a marked increase in adrenergic tone. "	( Treatment of cardiovascular collapse from caffeine overdose with lidocaine, phenylephrine, and hemodialysis. Kapur, R; Smith, MD, 2009)	2.06
"Caffeine can safely enhance the cytocidal effects of anticancer drugs through its DNA repair-inhibiting effect. "	( Impact of serum caffeine monitoring on adverse effects and chemotherapeutic responses to caffeine-potentiated chemotherapy for osteosarcoma. Hayashi, K; Kawahara, M; Miyamoto, K; Shirai, T; Takeuchi, A; Tomita, K; Tsuchiya, H; Yamamoto, N; Yamauchi, K, 2009)	2.14
"Caffeine did not inhibit the differentiation of 3T3-L1 pre-adipocytes to mature adipocytes, but it did suppress the intracellular lipid accumulation after complete differentiation in a dose-dependent manner (0.125-1.0 mM)."	( Inhibitory effects of caffeine and its metabolites on intracellular lipid accumulation in murine 3T3-L1 adipocytes. Ashida, H; Hashimoto, T; Kanazawa, K; Nakabayashi, H; Nishiumi, S, 2008)	1.38
"Caffeine was found to enhance performance, but only when participants were accurately told they were receiving it."	( Pre-existent expectancy effects in the relationship between caffeine and performance. Ash, J; Elliman, NA; Green, MW, 2010)	1.32
"Caffeine did not increase alertness in NL participants."	( Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption. Deckert, J; Evershed, RP; Heatherley, SV; Hohoff, C; Maxfield, PJ; Mullings, EL; Nutt, DJ; Rogers, PJ, 2010)	1.33
"Caffeine was used to activate RyRs and the intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured in both freshly isolated and cultured mouse aortic SMCs (ASMCs)."	( Modulation of Ca(2+) release through ryanodine receptors in vascular smooth muscle by protein kinase Calpha. Kirber, MT; Peng, H; Yaney, GC, 2010)	1.08
"Caffeine was found to increase adenosine deaminase activity."	( Rapid determination of adenosine deaminase kinetics using fast-scan cyclic voltammetry. Venton, BJ; Xu, Y, 2010)	1.08
"Caffeine did not enhance apoptosis, transaminase activity, or histopathological injury of normal rat liver tissue at any time points after IR."	( Caffeine does not enhance radiosensitivity of normal liver tissue in vivo. Ding, WJ; Du, SS; Jiang, W; Liu, ZS; Qiang, M; Wang, TJ; Zeng, HY; Zeng, ZC; Zhou, LY, 2011)	2.53
"Caffeine could also increase the cyclooxygenase-2 (COX-2) protein expression and prostaglandin (PG)E(2) production in cultured neonatal mouse calvariae."	( Caffeine enhances osteoclast differentiation from bone marrow hematopoietic cells and reduces bone mineral density in growing rats. Chen, C; Liu, SH; Tsai, C; Yang, RS; Yang, YT; Yen, YP, 2011)	2.53
"Caffeine is known to inhibit cyclic nucleotide phosphodiesterases (PDEs), leading to an increase in cytosolic cAMP and stimulation of downstream cAMP-dependent mechanisms."	( Inhibitory effect of caffeine on pacemaker activity in the oviduct is mediated by cAMP-regulated conductances. Britton, F; Dixon, R; Hwang, S; Sanders, K; Ward, S, 2011)	1.41
"Caffeine intake may increase the risk of sine causa recurrent miscarriage regardless of pregnancy-related symptoms and relevant covariates (such as age and tobacco use)."	( Maternal caffeine consumption and sine causa recurrent miscarriage. Caramellino, L; Menato, G; Patriarca, A; Stefanidou, EM, 2011)	2.23
"This caffeine-induced increase in force could provide similar benefit across a range of exercise intensities, with greater gains likely in activities powered by slower muscle fiber type."	( The effect of physiological concentrations of caffeine on the power output of maximally and submaximally stimulated mouse EDL (fast) and soleus (slow) muscle. Cox, VM; Duncan, MJ; James, RS; Tallis, J, 2012)	1.09
"Caffeine produced an increase in SCL, and this increase did not differ between the groups."	( Caffeine effects on resting-state electrodermal levels in AD/HD suggest an anomalous arousal mechanism. Barry, RJ; Clarke, AR; Dupuy, FE; MacDonald, B; McCarthy, R; Selikowitz, M, 2012)	2.54
"Caffeine is thought to increase the antitumor effect of cisplatin or DNA-damaging agents because it is known that caffeine inhibits DNA repair. "	( Caffeine increases the antitumor effect of Cisplatin in human hepatocellular carcinoma cells. Arimori, K; Ichimiya, A; Iwakiri, T; Kawano, Y; Kohno, T; Nagata, M; Okumura, M, 2012)	3.26
"Caffeine promotes dendritic spine growth in cultured hippocampal neurons, which suggests a neuroprotective effect."	( Chronic caffeine treatment prevents stress-induced LTP impairment: the critical role of phosphorylated CaMKII and BDNF. Aleisa, AM; Alkadhi, KA; Alzoubi, KH; Srivareerat, M, 2013)	1.55
"The caffeine-induced increase in adrenaline could be responsible for the higher increase in IL-6 levels, as well as for the increased lactate levels."	( Effects of caffeine on the inflammatory response induced by a 15-km run competition. Aguiló, A; Martínez, P; Martínez, S; Monjo, M; Moreno, C; Tauler, P, 2013)	1.26
"Caffeine appears to enhance the discriminative-stimulus effects of the threshold dose of nicotine by a pharmacodynamic rather than a pharmacokinetic interaction. "	( Caffeine potentiates the discriminative-stimulus effects of nicotine in rats. Gasior, M; Goldberg, SR; Jaszyna, M; Munzar, P; Witkin, JM, 2002)	3.2
"The caffeine-mediated increase in APAP toxicity was similar in cells treated with ethanol or isopentanol alone or in combination."	( Effect of caffeine on acetaminophen hepatotoxicity in cultured hepatocytes treated with ethanol and isopentanol. Bement, J; Chatfield, K; DiPetrillo, K; Jeffery, E; Kostrubsky, V; Sinclair, J; Sinclair, P; Wood, S; Wrighton, S, 2002)	1.2
"Caffeine caused AIx to increase by 7 +/- 2 and 0 +/- 1%, respectively (P <.05), and pressure amplification to decrease by 1.0 +/- 0.1 v 0.2 +/- 0.2 (P <.001) placebo at 45 min."	( Acute caffeine intake influences central more than peripheral blood pressure in young adults. Goudsmit, J; Marwick, J; Maxwell, SR; Waring, WS; Webb, DJ, 2003)	1.52
"Caffeine may therefore cause persistent BP effects in persons who are regular consumers, even when daily intake is at moderately high levels."	( Blood pressure response to caffeine shows incomplete tolerance after short-term regular consumption. Lovallo, WR; McKey, BS; Sung, BH; Vincent, AS; Whitsett, TL; Wilson, MF, 2004)	1.34
"The caffeine-associated increase in HRV was not statistically different between the control and the type 1 diabetes groups (P = 0.16)."	( Influence of caffeine on heart rate variability in patients with long-standing type 1 diabetes. Kerr, D; Meckes, C; Richardson, T; Rozkovec, A; Ryder, J; Thomas, P, 2004)	1.17
"In caffeine group, an increase in the baseline Rf in presence of the pons and no change in medullary-spinal cord preparations have been observed."	( Involvement of adenosinergic A1 systems in the occurrence of respiratory perturbations encountered in newborns following an in utero caffeine exposure. a study on brainstem-spinal cord preparations isolated from newborn rats. Bodineau, L; Frugière, A; Gaytan, S; Gros, F; Saadani-Makki, F, 2004)	1.04
"Caffeine can cause anxiety symptoms in normal individuals, especially in vulnerable patients, like those with pre-existing anxiety disorders."	( Caffeine and psychiatric symptoms: a review. Benjamin, AB; Broderick, P, 2004)	2.49
"Caffeine can cause or worsen psychiatric symptoms but also has the potential to interact with many psychiatric medications. "	( Caffeine and psychiatric medication interactions: a review. Benjamin, AB; Broderick, PJ; Dennis, LW, 2005)	3.21
"Caffeine could enhance the anti-tumor effect of cisplatin in rat osteosarcoma."	( [Enhancement effect of caffeine on chemotherapy of osteosarcoma in Fischer 344/N rats]. Chen, J; Fan, SW; Gu, CL; Wan, SL, 2005)	2.08
"Caffeine is likely to produce substantial enhancement of several aspects of high-intensity team-sport performance."	( Multiple effects of caffeine on simulated high-intensity team-sport performance. Cairns, SP; Cook, C; Hopkins, WG; Stuart, GR, 2005)	2.09
"Caffeine could inhibit camptothecin-induced apoptosis of Molt-4 cells. "	( [Effect of caffeine on camptothecin-induced apoptosis of Molt-4 cells]. Feng, YD; Gong, JP; Tan, HL; Tao, DD; Xiao, H; Xie, DX; Yu, CN, 2005)	2.16
"Caffeine promotes hyperthermia and lethality when co-administered with the recreational drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") to rats. "	( Caffeine induces a profound and persistent tachycardia in response to MDMA ("Ecstasy") administration. Harkin, A; Maginn, M; McNamara, R, 2007)	3.23
"Caffeine can cause different mental disorders such as dependence, which is not included in the DSM-IV-R, withdrawal syndrome and intoxication."	( [Caffeine: a nutrient, a drug or a drug of abuse]. Alvarez García, Y; Barral Tafalla, D; Farré Albaladejo, M; Pardo Lozano, R, 2007)	1.97
"Caffeine does not produce any effect on the light fraction containing no fragments of terminal cisterns."	( [Intracellular localization of the caffeine-sensitive form of Ca-dependent ATPase in the sarcoplasmic reticulum]. Budina, NB; Ritov, VB; Vekshina, OM, 1984)	1.27
"Caffeine appears to enhance lipid metabolism."	( Applied physiology of cycling. Faria, IE, )	0.85
"Caffeine was found to suppress the cell cycle effects of the cancer chemotherapeutic agent neocarzinostatin (NCS). "	( Effects of caffeine on neocarzinostatin-induced inhibition of cell cycle traverse in HeLa-S3 cells. Ebina, T; Iseki, S; Ishida, N, 1980)	2.09
"Caffeine was used to inhibit calcium uptake by the sarcoplasmic reticulum (SR) and to stimulate SR calcium release."	( Effects of low sodium perfusion on cardiac caffeine sensitivity and calcium uptake. Duenas, C; Fintel, M; Langer, GA, 1984)	1.25
"Caffeine may produce symptoms of anxiety-nervousness without increasing central norepinephrine turnover."	( The effects of caffeine on plasma MHPG, subjective anxiety, autonomic symptoms and blood pressure in healthy humans. Charney, DS; Galloway, MP; Heninger, GR, 1984)	1.34
"3. Caffeine can produce sarcomeric oscillations in K depolarized muscle fibres and, to a limited extent, in glycerol-treated muscle fibres."	( Action of caffeine in excitation-contraction coupling of frog skeletal muscle fibres. Kumbaraci, NM; Nastuk, WL, 1982)	1.18
"Caffeine tended to increase the rate pressure product from 6873 +/- 1494 to 7566 +/- 1102 (p = 0.051), whereas resting myocardial blood flow remained unchanged (0.61 +/- 0.13 versus 0.58 +/- 0.07 ml/g/min, p = ns). "	( Effect of caffeine on myocardial blood flow at rest and during pharmacological vasodilation. Böttcher, M; Czernin, J; Phelps, ME; Schelbert, HR; Sun, KT, 1995)	2.14
"Caffeine did not activate 45Ca2+ release although ryanodine induced 45Ca2+ release and CICR was augmented in the presence of caffeine."	( The modulation and characterisation of the Ca(2+)-induced Ca2+ release mechanism in cultured human myometrial smooth muscle cells. Gillespie, JI; Morgan, JM, 1995)	1.01
"The caffeine-induced increase in [Ca2+]i was not attenuated by the removal of extracellular Ca2+ and did not stimulate the rate of Mn2+ quench of fura-2 fluorescence."	( Caffeine-evoked, calcium-sensitive membrane currents in rabbit aortic endothelial cells. Adams, DJ; Rusko, J; Van Slooten, G, 1995)	2.21
"Caffeine did not produce an anti-inflammatory effect as determined by hindpaw plethysmometry, suggesting that antinociception was not secondary to an anti-inflammatory action."	( Caffeine antinociception in the rat hot-plate and formalin tests and locomotor stimulation: involvement of noradrenergic mechanisms. Doak, GJ; Reid, AR; Sawynok, J, 1995)	2.46
"Caffeine alone did not produce any significant modification in functional impairment but the co-administration significantly increased the effect of naproxen."	( Usefulness of the pain-induced functional impairment model to relate plasma levels of analgesics to their efficacy in rats. Hoyo-Vadillo, C; López-Munoz, FJ; Pérez-Urizar, J, 1995)	1.01
"7. Caffeine failed to inhibit the augmentations of aspartate- and N-methyl-D-aspartate (NMDA) -gated current by glycine, suggesting that caffeine has no effect on the allosteric glycine binding site on the NMDA receptor."	( Caffeine and related compounds block inhibitory amino acid-gated Cl- currents in freshly dissociated rat hippocampal neurones. Akaike, N; Harata, N; Uneyama, H, 1993)	2.24
"Caffeine did not produce a significant effect on cell cycle progression up to 8 h after UV irradiation, but it caused a distinct block in early S phase during the 24 h post-irradiation period."	( Caffeine inhibits gene-specific repair of UV-induced DNA damage in hamster cells and in human xeroderma pigmentosum group C cells. Bohr, VA; Cook, JA; Evans, MK; Link, CJ; Muldoon, R; Stevnsner, T, 1995)	2.46
"Caffeine produced an increase in self-reported muscular tension and tended to increase anxiety and delta magnitude."	( Caffeine and smoking: subjective, performance, and psychophysiological effects. Davis, RA; deBethizy, JD; Pritchard, WS; Robinson, JH; Stiles, MF, 1995)	2.46
"Caffeine inhibited the increase in the resting tone without blocking the refilling process of the stores at 37 degrees C, but at 25 degrees C a partial inhibition of the repletion of internal Ca2+ pools was observed."	( Effects of different agents on the contractile response elicited by extracellular calcium after depletion of internal calcium stores in rat isolated aorta. D'Ocon, MP; Noguera, MA, 1993)	1.01
"Caffeine is able to increase muscle contractility, has no ergogenic effect on intense exercise of brief duration, but can improve the time before exhaustion."	( Caffeine and sports activity: a review. Debry, G; Nehlig, A, 1994)	2.45
"Isocaffeine did not produce a rise of [Ca2+]i."	( Comparison of the effects of caffeine and other methylxanthines on [Ca2+]i in rat ventricular myocytes. Dilly, KW; Donoso, P; Eisner, DA; Negretti, N; O'Neill, SC, 1994)	1.09
"Caffeine failed to produce an inward current and Ca2+ transient after treatment with extracellular ryanodine."	( Chloride currents activated by caffeine in rat intestinal smooth muscle cells. Ito, S; Nakazato, Y; Ohta, T, 1993)	1.29
"Caffeine caused an increase in force only in < 20 Hz, but a decrease in 50 and 100 Hz."	( The effects of theophylline and caffeine on the isolated rat diaphragm. Gölgeli, A; Ozesmi, C; Ozesmi, M, 1995)	1.3
"3. Caffeine was able to produce a release of Ca2+ from the internal store of guinea-pig ureter and elicit contraction."	( Major difference between rat and guinea-pig ureter in the ability of agonists and caffeine to release Ca2+ and influence force. Burdyga, TV; Taggart, MJ; Wray, S, 1995)	1.03
"Caffeine is known to inhibit replication of herpes simplex virus (HSV)-1 and the therapeutic efficacy of caffeine (Cafon) gel has been shown in a mouse model cutaneously infected with HSV-1. "	( Efficacy of Cafon gel on cutaneous infection with herpes simplex virus (HSV)-2 and acyclovir-resistant HSV in mice. Kawana, T; Koyasu, M; Obara, Y; Sato, H; Sekiguchi, H; Shiraki, K; Yamamura, J; Yoshida, Y, 1996)	1.74
"But, caffeine did not suppress [Ca2+]i rise and activation of I(K.Ca) induced by A23187 or inositol trisphosphate (IP3)."	( Effect of caffeine on mucus secretion and agonist-dependent Ca2+ mobilization in human gastric mucus secreting cells. Hamada, E; Hata, Y; Hazama, H; Iwasawa, K; Nakajima, T; Omata, M; Ota, S; Takahashi, M, 1997)	1.15
"Caffeine did not enhance the analgesic effect of aspirin."	( Do codeine and caffeine enhance the analgesic effect of aspirin?--A systematic overview. Po, AL; Zhang, WY, 1997)	1.37
"Caffeine did not increase cocaine-like effect or desire-for-cocaine ratings among the FCD subjects."	( Subjective effects of oral caffeine in formerly cocaine-dependent humans. Callas, P; Goldberg, K; Hughes, JR; Liguori, A, 1997)	1.32
"Caffeine did not produce any increase in Ca2+ release or [Ca2+]i rise in any preparation."	( Cyclic ADP-ribose induces Ca2+ release from caffeine-insensitive Ca2+ pools in canine salivary gland cells. Akagawa, Y; Dohi, T; Imai, Y; Itadani, K; Kitayama, S; Morita, K; Yamaki, H, 1998)	1.28
"Caffeine induced an increase in locomotor activity in a dose-dependent manner up to doses of 30 mg/kg and a decline at 75 mg/kg."	( Immunohistochemical localization of caffeine-induced c-Fos protein expression in the rat brain. Bennett, HJ; Semba, K, 1998)	1.3
"Caffeine was found to enhance lipolysis through acting on lipid droplets but not on HSL."	( Anti-obesity action of oolong tea. Han, LK; Kimura, Y; Li, J; Okuda, H; Takaku, T, 1999)	1.02
"Caffeine failed to cause a distinct peak of endothelin production within 20 minutes."	( Production of endothelin by cultured human endothelial cells following exposure to nicotine or caffeine. Lee, WO; Wright, SM, 1999)	1.24
"Caffeine, which promotes Ca(2+) release from intracellular stores, had concentration-dependent effects."	( Calcium release from internal stores is required for the generation of spontaneous hyperpolarizations in dopaminergic neurons of neonatal rats. Dresse, A; Massotte, L; Mkahli, F; Seutin, V, 2000)	1.03
"Caffeine was found to enhance performance on visual search (p<0.05) but not on the chartsearch, although a significant correlation was found between performance on the two tests (p<0.05)."	( Effects of alcohol and caffeine on maritime navigational skills. Leach, J; Marsden, G, 2000)	1.34
"Caffeine did not enhance fertility or prolificacy, regardless of its ability to increase sperm motility."	( Effects of added caffeine on results following artificial insemination with fresh and refrigerated rabbit semen. Alvariño, JM; López, FJ, 2000)	1.37
"Caffeine does not inhibit Chk2/Cds1 activity directly, but rather, blocks the activation of Chk2/Cds1 by inhibiting ATM kinase activity."	( Caffeine abolishes the mammalian G(2)/M DNA damage checkpoint by inhibiting ataxia-telangiectasia-mutated kinase activity. Chaturvedi, P; Johanson, RA; Khanna, KK; Mattern, MR; Mishra, R; Scott, SP; Spring, K; Winkler, JD; Zhou, BB, 2000)	2.47
"Caffeine did not inhibit these kinases in vitro but did inhibit Rad3, a kinase that regulates Cds1 and Chk1."	( Mechanism of caffeine-induced checkpoint override in fission yeast. Baber-Furnari, B; Brondello, JM; Moser, BA; Russell, P, 2000)	1.4
"Caffeine is known to produce various effects on the gastrointestinal tract. "	( Effects of caffeine on gastrointestinal myoelectric activity and colonic spike activity in dogs. Abo, M; Chen, JD; Kono, T; Lu, CL, 2000)	2.14
"Caffeine, which promotes the release of sarcoplasmic reticulum (SR) calcium, increased contractile force eightfold at all three temperatures, but the SR blocker ryanodine was only inhibitory at 4 degrees C."	( Effects of temperature and calcium availability on ventricular myocardium from rainbow trout. Cameron, JS; Coyne, MD; Gwathmey, JK; Kim, CS, 2000)	1.03
"The caffeine-induced increase in [Ca2+], was enhanced in the presence of halothane (> or = 1%), enflurane (> or = 1%), and isoflurane (> or = 3%) but was attenuated in the presence of sevoflurane (> or = 3%)."	( Comparison of volatile anesthetic actions on intracellular calcium stores of vascular smooth muscle: investigation in isolated systemic resistance arteries. Akata, T; Izumi, K; Nakashima, M, 2001)	0.79
"A caffeine-induced increase in cytosolic-free Ca(2+) concentration ([Ca(2+)](i)) is considered diagnostic evidence of the existence of CICR."	( A novel Ca(2+) influx pathway in mammalian primary sensory neurons is activated by caffeine. Hoesch, RE; Kao, JP; Weinreich, D, 2001)	1.09
"Caffeine may increase an individual's sensitivity to hypoglycemia through the combined effects of reducing substrate delivery to the brain via constriction of the cerebral arteries, whilst simultaneously increasing brain glucose metabolism and augmenting catecholamine production."	( The best defense against hypoglycemia is to recognize it: is caffeine useful? Kerr, D; Watson, J, 1999)	1.27
"With caffeine, however, the increase in intracellular calcium was not evident unless the mitochondria were depolarized."	( Interference with calcium-dependent mitochondrial bioenergetics in cardiac myocytes isolated from doxorubicin-treated rats. Heller, LJ; Wallace, KB; Zhou, S, 2001)	0.77
"Caffeine can enhance mean arterial blood pressure (MAP) and attenuate forearm blood flow (FBF) and forearm vascular conductance (FVC) during exercise in thermal neutral conditions without altering body temperature. "	( Effects of caffeine and high ambient temperature on haemodynamic and body temperature responses to dynamic exercise. Daniels, JW; Lewis, W; Stebbins, CL, 2001)	2.14
"Caffeine is known to inhibit phosphodiesterases, to mobilise intracellular calcium, and to act as an antagonist at adenosine receptors, all of which can potentially alter nitric oxide (NO) production. "	( Caffeine decreases exhaled nitric oxide. Bruce, C; Thomas, PS; Yates, DH, 2002)	3.2
"Caffeine is known to activate influx of both mono- and divalent cations in various cell types, suggesting that this xanthine opens non-selective cation channels at the plasma membrane. "	( Caffeine activates a mechanosensitive Ca(2+) channel in human red cells. Cordero, JF; Romero, PJ, 2002)	3.2
"Caffeine did not increase the intracellular cyclic AMP level, while theophylline did significantly when added to a presporulation medium containing glucose."	( Comparative studies on sporulation-promotive actions on cyclic AMP, theophylline and caffeine in Saccharomyces cerevisiae. Tsuboi, M; Yanagishima, N, 1975)	1.2
"Caffeine did not inhibit postreplication repair in either strain, as determined by sedimentation profile studies of DNA on alkaline sucrose gradients."	( The absence of caffeine inhibition of post-replication repair in excision deficient strains of Escherichia coli B and K12. Johnson, RC; McCulley, CM, 1976)	1.33
"(2) Caffeine, known to enhance Ca2+ efflux from and inhibit Ca2+ uptake into intracellular stores, greatly accelerates the decay of the potentiated state during a rest period."	( The decay of the potentiated state in sheep and calf ventricular myocardial fibers. Influence of agents acting on transmembrane Ca2+ flux. Bass, O, 1976)	0.74
"3. Caffeine inhibited the increase in [Ca2+]i and tension development during 118 mM-K+ depolarization, in a concentration-dependent manner."	( Mechanisms of caffeine-induced contraction and relaxation of rat aortic smooth muscle. Hirano, K; Kanaide, H; Kobayashi, S; Watanabe, C; Yamamoto, H, 1992)	1.16
"Caffeine did not increase the severity of symptoms but did decrease the severity of withdrawal-induced hunger."	( Effects of caffeine on tobacco withdrawal. Bickel, WK; Fenwick, JW; Higgins, ST; Hughes, JR; Oliveto, AH; Pepper, SL; Terry, SY, 1991)	1.39
"Caffeine was found to inhibit both type I and type II topoisomerases in vivo as judged by its effects on replicating simian virus 40 (SV40) chromosomes. "	( Rapid evaluation of topoisomerase inhibitors: caffeine inhibition of topoisomerases in vivo. Shin, CG; Snapka, RM; Strayer, JM; Wani, MA, 1990)	1.98
"Thus caffeine appeared to produce a dose-dependent biphasic effect; a lower dose was rewarding, whereas higher doses produced aversions to environmental stimuli associated with the drug."	( Caffeine-induced place and taste conditioning: production of dose-dependent preference and aversion. Beninger, RJ; Brockwell, NT; Eikelboom, R, 1991)	2.18
"Caffeine did not increase the nephrotoxicity of CDDP, and no insomnia nor palpitation was seen."	( [Intra-arterial infusion of cisplatin and caffeine for a recurrent malignant fibrous histiocytoma]. Morikawa, S; Morishita, H; Ono, M; Takagi, Y; Tomita, K; Tsuchida, T; Tsuchiya, H; Yasutake, H, 1990)	1.26
"The caffeine-induced increase in Ca2+ transients, however, was delayed in both diabetic muscles and non-diabetic denervated muscles."	( Increase in electrically-stimulated Ca2+ release and suppression of caffeine response in diaphragm muscle of alloxan-diabetic mice compared with the denervation effect. Kimura, I; Kimura, M, 1990)	1
"Caffeine led to an increase in the mean arterial blood pressure on the first 3 days of therapy, but the heart rate did not change."	( Cardiovascular effects of caffeine therapy in preterm infants. Erickson, R; Sims, ME; Walther, FJ, 1990)	1.3
"Caffeine may inhibit noradrenalineinduced Ca2' release."	( Inhibitory effects of caffeine on contractions and calcium movement in vascular and intestinal smooth muscle. Ahn, HY; Karaki, H; Urakawa, N, 1988)	1.31
"Caffeine does not produce amphetamine-like stereotypy."	( Another look at amphetamine-induced stereotyped locomotor activity in rats using a new statistic to measure locomotor stereotypy. Cross, DR; Hollingsworth, EM; Mueller, K, 1989)	1
"Caffeine did not enhance the expression of the fra(X) in the PBLC or in the three LCL from fra(X) expressing individuals nor did it elicit fra(X) expression in LCL from a non-expressing obligate-carrier female and a transmitting male."	( The effect of caffeine on fragile X expression. Abruzzo, MA; Jacobs, PA; Mayer, M; Pettay, D, 1986)	1.35
"Caffeine can produce a mild hypertensive effect for a few hours after use. "	( Caffeine-containing beverages and the prevalence of hypertension. Birkett, NJ; Logan, AG, 1988)	3.16
"Caffeine may cause anxiety and panic in panic disorder patients and may aggravate the symptoms of premenstrual syndrome."	( Psychotropic effects of caffeine. Clementz, GL; Dailey, JW, 1988)	1.3
"Caffeine was found to increase attention and vigilance by augmenting the number of repetitions of responses to a verbal stimulus in a free word association test."	( Attentional effects of caffeine in man: comparison with drugs acting upon performance. Bielecki, M; Moulin, M; Pons, L; Potier, JC; Trenque, T, 1988)	1.31
"Both caffeine and L2 inhibit thromboxane formation in whole blood in a dose dependent fashion."	( A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Afzal, M; Ali, M, 1987)	0.73
"Caffeine was found to inhibit the rejoining of dsb even after 6 h but the length of G2 phase was normal."	( Relationship between double strand break rejoining and G2 block formation in V79 cells. Coquerelle, TM; Weibezahn, KF, 1986)	0.99
"Caffeine did not inhibit the binding of [3H]spiperone to membranes or the accumulation of L-DOPA in the striatum, produced by gamma-butyrolactone."	( Caffeine mimics dopamine receptor agonists without stimulation of dopamine receptors. Uramoto, H; Watanabe, H, 1986)	2.44
"The caffeine-induced increase in Ca2+-aequorin luminescence was inhibited by GLR, but not by PF."	( Decreasing effects by glycyrrhizin and paeoniflorin on intracellular Ca2+-aequorin luminescence transients with or without caffeine in directly stimulated-diaphragm muscle of mouse. Kimura, I; Kimura, M, 1985)	0.96

Treatment

Caffeine treatment increases attention and improves learning, memory, and olfactory discrimination without altering blood pressure and body weight. Caffeine-treated rats had increased locomotor activity, speed, and changed grooming behavior.

Excerpt	Reference	Relevance
"Caffeine treatments of Swiss mice reduced leukocyte infiltration into the peritoneal cavity after L."	( Anti-inflammatory activity of caffeine (1,3,7-trimethylxanthine) after experimental challenge with virulent Listeria monocytogenes in Swiss mice. de Alcântara Almeida, I; Mancebo Dorvigny, B; Nunes Santana, L; Souza Tavares, L; Vitor Lima-Filho, J, 2021)	1.63
"Caffeine treatment increases attention and improves learning, memory, and olfactory discrimination without altering blood pressure and body weight."	( Effects of Caffeine Consumption on Attention Deficit Hyperactivity Disorder (ADHD) Treatment: A Systematic Review of Animal Studies. López Palomé, J; Martin de la Torre, O; Redolar-Ripoll, D; Vázquez, JC, 2022)	1.83
"Caffeine treated animals performed worse on open field test compared to the controls (SDM -1.11(95%CI -3.01 to 0.80))."	( The effects of caffeine following hypoxic-ischemic encephalopathy: A systematic review of animal studies. Bruschettini, M; Moreira, A; Mustafa, S; Pizarro, AB; Romantsik, O, 2022)	1.8
"Caffeine was pre-treated in L02 cells or mice."	( Caffeine alleviates acute liver injury by inducing the expression of NEDD4L and deceasing GRP78 level via ubiquitination. Cao, LP; Fu, YM; Hu, XW; Li, J; Li, XM; Long, H; Wang, AM; Xiong, YH; Xu, J; Zeng, F; Zhang, FJ, 2022)	2.89
"Caffeine treatment induced the expression of NEDD4L, resulting in the ubiquitination and inhibition of GRP78."	( Caffeine alleviates acute liver injury by inducing the expression of NEDD4L and deceasing GRP78 level via ubiquitination. Cao, LP; Fu, YM; Hu, XW; Li, J; Li, XM; Long, H; Wang, AM; Xiong, YH; Xu, J; Zeng, F; Zhang, FJ, 2022)	2.89
"Caffeine treatment and FOXM1 inhibition can both enhance the antitumor effect of statins by blocking the molecular and metabolic processes that confer statin resistance, indicating potential combination therapeutic strategies for neuroblastoma. "	( Caffeine Supplementation and FOXM1 Inhibition Enhance the Antitumor Effect of Statins in Neuroblastoma. Ding, HF; Ding, J; Dong, Z; Liu, K; Liu, M; Sudarshan, S; Tran, GB; Ye, B; Yu, Y; Zha, Y, 2023)	3.8
"Caffeine-treated rats had increased locomotor activity, speed, and changed grooming behavior."	( Effects of caffeine on intracranial pressure and pain perception in freely moving rats. Eftekhari, S; Israelsen, IME; Jensen, RH; Kamp-Jensen, C; Westgate, CSJ, 2023)	2.02
"Caffeine (30 mg/kg) treated control animals showed depressive, anxiety-like behaviour and cognitive impairments."	( Repeated caffeine administration aggravates post-traumatic stress disorder-like symptoms in rats. Dangi, DS; Krishnamurthy, S; Prajapati, SK, 2019)	1.65
"Caffeine treatment evoked significant elevation of brain MDA levels in the zebrafish brain, and TPH treatment prevented this increase."	( Oxidative Stress Mediates Anxiety-Like Behavior Induced by High Caffeine Intake in Zebrafish: Protective Effect of Alpha-Tocopherol. Assad, N; Bahia, CP; Brasil, A; Cardoso, PB; de Carvalho, TS; de Jesus Oliveira Batista, E; Gouveia, A; Herculano, AM; Kauffmann, N; Lima-Bastos, S; Luz, WL; Moraes, S; Oliveira, KRMH; Passos, A; Santos-Silva, M, 2019)	1.47
"Caffeine treatment in BRA could be considered as a local standard practice. "	( Caffeine treatment for bronchiolitis-related apnea in the pediatric intensive care unit. Brossier, D; Denis, M; Faucon, C; Goyer, I; Heuzé, N; Jokic, M; Porcheret, F, 2020)	3.44
"Caffeine treatment and postmenstrual age of the infant were important covariates in all models."	( Clinical validation of the Neonatal Infant Stressor Scale with preterm infant salivary cortisol. D'Agostino, M; Liu, SH; Pourkaviani, S; Satty, RE; Spear, EA; Stroustrup, A; Zhang, X, 2020)	1.28
"Caffeine treatment rendered cells significantly better at performing the nascent DNA synthesis that accompanies the early strand invasion steps of HR."	( The dichotomous effects of caffeine on homologous recombination in mammalian cells. Baker, MD; Magwood, AC; Mosser, DD; Mundia, MM; Pladwig, SM, 2020)	1.58
"Caffeine-treated male mice had substantially higher fecal corticosterone and urinary 8-hydroxydeoxyguanosine at 14 weeks, suggestive of chronic stress."	( Effects of Neonatal Caffeine Administration on Vessel Reactivity in Adult Mice. Berkelhamer, S; Chandrasekharan, P; Gugino, S; Kumar, VHS; Nielsen, L; Singh, AP; Wang, H, 2021)	1.67
"Caffeine is a common treatment for neonatal intensive care management of the developmental complication of apnea of prematurity in preterm infants. "	( Caffeine for the Treatment of Apnea in the Neonatal Intensive Care Unit: A Systematic Overview of Meta-Analyses. Abushanab, D; Al-Badriyeh, D; Al-Shaibi, S; Alhersh, E, 2020)	3.44
"Caffeine treatment can protect hyperoxia-induced mice lung from oxidative injury by inhibiting NLRP3 inflammasome and NF-κB pathway."	( Caffeine prevents hyperoxia-induced lung injury in neonatal mice through NLRP3 inflammasome and NF-κB pathway. Chen, S; Du, L; Li, C; Wu, Q; Zhong, D, 2020)	3.44
"Postcaffeine treatment with propranolol was associated with performance improvement; however, surgical performance remained inferior compared with low-dose propranolol alone for total surgical score (570.0 vs 617.0; difference, -51.0; 95% CI, -77.6 to -24.4; P = .01), tremor-specific score (50.0 vs 75.0; difference, -16.0; 95% CI, -31.8 to -0.2; P = .03), and intraocular trajectory (2265.9 mm vs 2080.7 mm; difference, 166.8 mm; 95% CI, 64.1-269.6 mm; P = .03)."	( Association of Weight-Adjusted Caffeine and β-Blocker Use With Ophthalmology Fellow Performance During Simulated Vitreoretinal Microsurgery. Belfort, R; Dias Gomes Barrios Marin, V; Faber, J; Farah, ME; Gehlbach, PL; Grupenmacher, AT; Jiramongkolchai, K; Maia, M; Muralha, F; Roizenblatt, M, 2020)	1.33
"Caffeine-treated and -untreated pups underwent the Vannucci procedure (unilateral carotid ligation, global hypoxia) on P2."	( Caffeine Restores Background EEG Activity Independent of Infarct Reduction after Neonatal Hypoxic Ischemic Brain Injury. Gonzalez, F; McQuillen, PS; Sun, H, 2020)	2.72
"Caffeine-treated adolescent male rats were exposed to caffeine (0.25 g/L) in their drinking water beginning on P28."	( Pharmacological depletion of serotonin and norepinephrine with para-chlorophenylalanine and alpha-methyl-p-tyrosine reverses the antidepressant-like effects of adolescent caffeine exposure in the male rat. Abdulzahir, A; Hwang, K; Sanford, J; Turgeon, SM, 2020)	1.47
"Caffeine treatment is a preferred treatment choice."	( Therapy for Apnoea of Prematurity: A Retrospective Study on Effects of Standard Dose and Genetic Variability on Clinical Response to Caffeine Citrate in Chinese Preterm Infants. Chen, F; Cheng, R; Guo, HL; He, X; Jia, WW; Li, L; Liu, Y; Lu, KY; Ni, MM; Qiu, JC; Xu, J, 2021)	1.55
"Caffeine treatment is routinely used in premature infants to prevent development of apnea and bronchopulmonary dysplasia. "	( Effects of Different Onset Times of Early Caffeine Treatment on Mesenteric Tissue Oxygenation and Necrotizing Enterocolitis: A Prospective, Randomized Study. Cakir, SC; Cetinkaya, M; Koksal, N; Ozkan, H; Saglam, O, 2023)	2.62
"· Caffeine treatment that onset in the first 24 hours may be associated with NEC development.."	( Effects of Different Onset Times of Early Caffeine Treatment on Mesenteric Tissue Oxygenation and Necrotizing Enterocolitis: A Prospective, Randomized Study. Cakir, SC; Cetinkaya, M; Koksal, N; Ozkan, H; Saglam, O, 2023)	1.73
"Caffeine treatment significantly reduced mTORC1 signaling, total protein synthesis and myotube diameter in a CaMKKβ/AMPK-dependent manner."	( Acute high-caffeine exposure increases autophagic flux and reduces protein synthesis in C2C12 skeletal myotubes. Baumgarner, BL; Crocker, CL; Downs, RM; Hughes, MA; Kinsey, ST; Webb, GW, 2017)	1.57
"Caffeine treatment in the newborn period improves expiratory flow rates in midchildhood, which seems to be achieved by improving respiratory health in the newborn period. "	( Neonatal Caffeine Treatment and Respiratory Function at 11 Years in Children under 1,251 g at Birth. Cheong, JLY; Doyle, LW; Ranganathan, S, 2017)	2.31
"Caffeine pretreatment did not change seizure latency and seizure duration."	( The Effects of Adenosinergic Modulation on Cytokine Levels in a Pentylenetetrazole-Induced Generalized Tonic-Clonic Seizure Model. Ateş, N; Dede, F; Eraldemir, FC; Karadenizli, S; Özsoy, ÖD; Şahin, D, 2017)	1.18
"Caffeine and taurine treatments resulted in significant differences between the control and ascorbic acid groups with respect to subjective daytime and nighttime activity (p<0.05)."	( Behavioral Changes and Survival in Drosophila melanogaster: Effects of Ascorbic Acid, Taurine, and Caffeine. Han, SH; Hong, KB; Shin, B; Suh, HJ; Woo, MJ, 2017)	1.39
"Caffeine treatment simultaneously ameliorates immune and metabolic pathogenic signals present in tissue to normalize immunolgical and metabolic abnormalities found in HFD-induced obese rats."	( Effects and mechanisms of caffeine to improve immunological and metabolic abnormalities in diet-induced obese rats. Hou, MC; Hsieh, YC; Huang, CC; Huang, SF; Lee, FY; Lee, KC; Lee, SD; Li, TH; Lin, HC; Lin, MW; Liu, CW; Su, YB; Tsai, CY; Tsai, HC; Yang, YY, 2018)	1.5
"Caffeine treatment significantly decreased the elevated serum ALT, AST, and bilirubin and increased the reduced albumin level."	( Caffeine affects HFD-induced hepatic steatosis by multifactorial intervention. Ayoub, SE; Elkashefand, WF; Helal, MG; Ibrahim, TM, 2018)	2.64
"Caffeine used in the treatment of apnea of prematurity was reported to decrease mechanical ventilation requirement, the frequencies of bronchopulmonary dysplasia, patent ductus arteriosus, cerebral palsy and neurodevelopmental disorders in very low birth weight infants."	( Caffeine prevents bilirubin-induced cytotoxicity in cultured newborn rat astrocytes. Akça, H; Deliktaş, M; Demiray, A; Ergin, H; Özdemir, MB; Özdemir, ÖMA, 2019)	2.68
"Caffeine treatment prevented RSV-mediated increase in CTGF mRNA."	( Increase in CTGF mRNA expression by respiratory syncytial virus infection is abrogated by caffeine in lung epithelial cells. Fehrholz, M; Glaser, K; Krempl, C; Kunzmann, S; Seidenspinner, S; Speer, CP, 2018)	1.42
"Both caffeine treatments (10 and 50 mg/L) increased the average speed and distance traveled when compared to the control group."	( Coffee time: Low caffeine dose promotes attention and focus in zebrafish. Luchiari, AC; Ruiz-Oliveira, J; Silva, PF, 2019)	1.31
"Caffeine treatment elicited MKP-1 down-regulation and PP2Acα up-regulation."	( Cross talk between p38MAPK and ERK is mediated through MAPK-mediated protein phosphatase 2A catalytic subunit α and MAPK phosphatase-1 expression in human leukemia U937 cells. Chang, LS; Chen, YJ; Cheng, TL; Lin, SR; Liu, WH, 2013)	1.11
"Caffeine treatment during SD, significantly increased early proliferative and post-mitotic stages of doublecortin (DCX) positive cells while modafinil treatment during SD, increased intermediate and post-mitotic stages of DCX positive cells compared to SD+Vehicle group."	( Caffeine and modafinil promote adult neuronal cell proliferation during 48 h of total sleep deprivation in rat dentate gyrus. Kauser, H; Kishore, K; Kumar, S; Panjwani, U; Ray, K; Sahu, S, 2013)	2.55
"Caffeine pretreatment induced higher mitogen-activated protein kinases (MAPK1 and MAPK3) phosphorylation and maturation-promoting factor activity at 12 hours and activated MAPK1 and maturation-promoting factor at 48 hours after culture in cumulus-oocyte complexes (COCs) compared with the control group (P < 0.05)."	( Influence of caffeine pretreatment on biphasic in vitro maturation of dog oocytes. Fouladi-Nashta, AA; Ghafari, F; Salavati, M; Zhang, T, 2013)	1.48
"Caffeine treatment also resulted in the loss of CHI3L1-associated AKT signaling pathway activation both in vitro and in vivo."	( Oral caffeine administration ameliorates acute colitis by suppressing chitinase 3-like 1 expression in intestinal epithelial cells. Kamba, A; Lee, IA; Llado, V; Low, D; Mizoguchi, E, 2014)	1.64
"Caffeine treatment exerted short-term stimulating effects and altered the trajectory of slow wave activity."	( The effects of caffeine on sleep and maturational markers in the rat. Huber, R; Kurth, S; Olini, N, 2013)	1.46
"Caffeine treatment at a daily dose of 10 and/or 20 mg/kg, sc was executed during postnatal days 7-11. "	( Different effects of postnatal caffeine treatment on two pentylenetetrazole-induced seizure models persist into adulthood. Kubová, H; Mareš, P; Tchekalarova, JD, 2013)	2.12
"Caffeine treatment increased inflammation and worsened alveolar hypoplasia in hyperoxia-exposed newborn mice. "	( Caffeine induces alveolar apoptosis in the hyperoxia-exposed developing mouse lung. Dayanim, S; Grewal, S; Londhe, VA; Lopez, B; Maisonet, TM, 2014)	3.29
"Caffeine treatment resulted in the recovery of fructose-induced decrease in nitric oxide production in the NTS."	( Caffeine intake improves fructose-induced hypertension and insulin resistance by enhancing central insulin signaling. Chen, BR; Cheng, PW; Cheng, WH; Ho, WY; Liou, JC; Liu, CP; Lu, PJ; Sun, GC; Tseng, CJ; Yeh, TC, 2014)	2.57
"This caffeine treatment results in serum levels equivalent to the consumption of 2-4 cups of coffee in humans."	( Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice. Buscariollo, DL; Fang, X; Greenwood, V; Rivkees, SA; Wendler, CC; Xue, H, 2014)	1.26
"Caffeine, standard treatment for apnea of prematurity, improves brainstem auditory processing. "	( Effects of caffeine treatment for apnea of prematurity on cortical speech-sound differentiation in preterm infants. Aschner, JL; Chan, J; Key, AP; Lambert, WE; Maitre, NL; Stark, AR, 2015)	2.25
"Caffeine-treated mice developed fewer tumors and milder inflammation than untreated mice."	( Increased expression and possible role of chitinase 3-like-1 in a colitis-associated carcinoma model. Huang, K; Li, C; Li, RH; Ma, JY; Tan, G; Zhi, FC, 2014)	1.12
"Caffeine treatment increased both RR and NG latency times."	( Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring. Bogo, MR; Bonan, CD; Capiotti, KM; Caumo, W; Da Silva, RS; De Oliveira, C; Kist, LW; Medeiros, LF; Scarabelot, VL; Souza, A; Souza, AC; Torres, IL, 2015)	1.56
"Caffeine-treated workers had higher protein concentrations."	( Unexpectedly strong effect of caffeine on the vitality of western honeybees (Apis mellifera). Bajda, M; Borsuk, G; Chobotow, J; Grzywnowicz, K; Krauze, M; Merska, M; Olszewski, K; Paleolog, J; Strachecka, A, 2014)	1.41
"Caffeine treatment before vitrification maintained the MPF activity at a level similar to that of fresh oocytes, and reduced the spontaneous parthenogenetic activation in comparison with oocytes that were not-treated with caffeine."	( Effect of caffeine treatment before vitrification on MPF and MAPK activity and spontaneous parthenogenetic activation of in vitro matured ovine oocytes. Ariu, F; Bebbere, D; Bogliolo, L; Falchi, L; Ledda, S; Leoni, G; Nieddu, SM; Pau, S; Zedda, MT, )	1.98
"Caffeine treatment prolongs the meiotic arrest of vitrified MII oocytes, likely via its action of stabilizing the MPF level."	( Effect of caffeine treatment before vitrification on MPF and MAPK activity and spontaneous parthenogenetic activation of in vitro matured ovine oocytes. Ariu, F; Bebbere, D; Bogliolo, L; Falchi, L; Ledda, S; Leoni, G; Nieddu, SM; Pau, S; Zedda, MT, )	1.98
"Caffeine treatment also induces dephosphorylation of Gln3 and its translocation to the nucleus and transcription of NCR-sensitive genes."	( Nuclear localization domains of GATA activator Gln3 are required for transcription of target genes through dephosphorylation in Saccharomyces cerevisiae. Harashima, S; Imabeppu, Y; Maekawa, H; Numamoto, M; Sasano, Y; Sugiyama, M; Tagami, S; Ueda, Y, 2015)	1.14
"• Caffeine therapy for treatment of apnea of prematurity has been well established over the past few years. "	( High versus low-dose caffeine for apnea of prematurity: a randomized controlled trial. Abdel-Hady, H; Mohammed, S; Nasef, N; Nour, I; Shabaan, AE; Shouman, B, 2015)	1.46
"Caffeine treatment significantly improved daytime alertness at adverse circadian phases (p <0.0001) but did not decrease the occurrence of daytime naps compared with placebo."	( Caffeine does not entrain the circadian clock but improves daytime alertness in blind patients with non-24-hour rhythms. Lockley, SW; St Hilaire, MA, 2015)	2.58
"Caffeine treatment also caused synaptic sites to depress during 1 Hz stimulation, consistent with inhibition of the usual mechanisms for replenishing vesicles at the active zone."	( Caffeine Modulates Vesicle Release and Recovery at Cerebellar Parallel Fibre Terminals, Independently of Calcium and Cyclic AMP Signalling. Balakrishnan, S; Bellamy, TC; Dobson, KL; Jackson, C, 2015)	2.58
"Caffeine treatment results in a rapid and sustained increase in diaphragmatic activity and Vt in preterm infants."	( The Effect of Caffeine on Diaphragmatic Activity and Tidal Volume in Preterm Infants. de Jongh, FH; Hutten, GJ; Kraaijenga, JV; van Kaam, AH, 2015)	2.22
"Caffeine treatment led to the rapid loss, by proteasomal degradation, of both Sae2, a nuclease that plays a role in early steps of resection, and Dna2, a nuclease that facilitates one of two extensive resection pathways."	( Caffeine impairs resection during DNA break repair by reducing the levels of nucleases Sae2 and Dna2. Bishop, DK; Eapen, VV; Haber, JE; Long, MJ; Mason, JM; Memisoglu, G; Tsabar, M; Waterman, DP, 2015)	2.58
"Caffeine treatment results in a dosage-dependent eviction of Rad51 from ssDNA."	( Caffeine inhibits gene conversion by displacing Rad51 from ssDNA. Bishop, DK; Chan, YL; Haber, JE; Mason, JM; Tsabar, M, 2015)	2.58
"Caffeine treatment was able to prevent CBD (5mg/kg) effects on memory when CBD was given after the training session."	( Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio). Antonioli, R; Bonan, CD; Capiotti, KM; Crippa, JA; da Silva, RS; Hallak, JE; Nazario, LR; Zuardi, AW, 2015)	2.58
"Caffeine-treated samples showed improved binding to phospholipids, a property likely to be important in cellular functioning of α-synuclein."	( Understanding Caffeine's Role in Attenuating the Toxicity of α-Synuclein Aggregates: Implications for Risk of Parkinson's Disease. Kardani, J; Roy, I, 2015)	1.5
"Caffeine treatment prevented the SD induced down-regulation of synaptophysin and synapsin I proteins with no change in PSD-95 protein in hippocampus."	( Caffeine and modafinil given during 48 h sleep deprivation modulate object recognition memory and synaptic proteins in the hippocampus of the rat. Kauser, H; Kumari, P; Panjwani, U; Ray, K; Sahu, S; Wadhwa, M, 2015)	2.58
"Caffeine binge treatment did not affect 5-HT-mediated inhibition."	( Modulation of GABA release from the thalamic reticular nucleus by cocaine and caffeine: role of serotonin receptors. Bisagno, V; Garcia-Rill, E; Gingrich, JA; Goitia, B; Rivero-Echeto, MC; Urbano, FJ; Weisstaub, NV, 2016)	1.38
"Caffeine is the main treatment for apnoea in preterm neonates, but its interactions with other respiratory stimulants like progesterone are unknown. "	( Inhibitory respiratory responses to progesterone and allopregnanolone in newborn rats chronically treated with caffeine. Bairam, A; Joseph, V; Uppari, N, 2016)	2.09
"The caffeine pretreatment showed significant protection against the reduction of paw grip strength in MPTP treated mice."	( Neuroprotective effects of caffeine in MPTP model of Parkinson's disease: A (13)C NMR study. Bagga, P; Chugani, AN; Patel, AB, 2016)	1.21
"Caffeine treatment at a high dose (30 mM) showed detrimental effects and caused early larval arrest."	( Caffeine Induces the Stress Response and Up-Regulates Heat Shock Proteins in Caenorhabditis elegans. Al-Amin, M; Gong, J; Kawasaki, I; Shim, YH, 2016)	2.6
"Caffeine in both treatment regimens caused hyperlocomotion only in male rats, whereas anxiety-related behavior was attenuated in both sexes by caffeine (1.0 g/L) throughout life."	( Caffeine exposure during rat brain development causes memory impairment in a sex selective manner that is offset by caffeine consumption throughout life. Ardais, AP; Borges, MF; Botton, PH; Cunha, RA; Fioreze, GT; Mioranzza, S; Nunes, F; Pagnussat, N; Porciúncula, Lde O; Rocha, AS; Sallaberry, C, 2016)	2.6
"Caffeine treatment also reduced the expression of pro-inflammatory genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-3, IL-6 and IL-12, and decreased both IL-6 secretion and phosphorylated p38MAPK expression in LPS-treated RAW264.7 cells."	( Caffeine prevents LPS-induced inflammatory responses in RAW264.7 cells and zebrafish. Hwang, JH; Kim, KJ; Lee, BY; Ryu, SJ, 2016)	2.6
"The caffeine citrate treatment group had a significantly shorter time of oxygen use and NCPAP support than the aminophylline treatment group (P<0.01)."	( [Effect of caffeine citrate on early pulmonary function in preterm infants with apnea]. Huang, JH; Wen, XH; Wu, WY; Yu, M; Zhang, XZ; Zhu, R, 2016)	1.31
"2 caffeine-treated broilers exposed to cold temperatures remarkably exhibited PHS incidences and developed RVH with right ventricular to total ventricular weight ratios of 30% or greater."	( Caffeine causes pulmonary hypertension syndrome (ascites) in broilers. Kamely, M; Rahimi, S; Torshizi, MA; Wideman, RF, 2016)	2.44
"The caffeine-polyphenol treatment resulted in significantly (p ≤ 0.05) greater energy expenditure (+7.99% rest; +10.16% post-SIE), V[Combining Dot Above]O2 (+9.64% rest; +12.10% post-SIE), and fat oxidation rate (+10.60% rest; +9.76% post-SIE) vs."	( Dietary Caffeine and Polyphenol Supplementation Enhances Overall Metabolic Rate and Lipid Oxidation at Rest and After a Bout of Sprint Interval Exercise. Directo, DJ; Hernandez, J; Higuera, D; Jo, E; Lewis, KL; Osmond, AD; Wong, M, 2016)	1.35
"Both caffeine pretreatments in chronic stressed rats, and chronic caffeine in acute stressed ones reduced the elevated myeloperoxidase activities (p<0.05-0.01)."	( Protective effect of low dose caffeine on psychological stress and cognitive function. Akakın, D; Ellek, N; Hamamcı, R; Kasimay Cakir, O; Kayalı, DG; Keleş, H; Özbeyli, D; Salehin, N; Yüksel, M, 2017)	1.2
"Caffeine treatment has reduced cell monolayer permeability after exposure to high glucose and desferoxamine as shown by TEER and FITC-dextran permeability assays."	( Caffeine Prevents Blood Retinal Barrier Damage in a Model, In Vitro, of Diabetic Macular Edema. Cavallaro, S; D'Agata, V; D'Amico, AG; Federico, C; La Cognata, V; Maugeri, G; Rasà, DM; Saccone, S, 2017)	2.62
"Caffeine treatment significantly improves outcome when compared to phosphate buffered saline."	( Single Dose Caffeine Protects the Neonatal Mouse Brain against Hypoxia Ischemia. Ådén, U; Fredholm, BB; Urmaliya, V; Winerdal, M; Winerdal, ME; Winqvist, O, 2017)	1.56
"Caffeine treatment was interrupted 24h before the object recognition task analysis."	( Caffeine improves adult mice performance in the object recognition task and increases BDNF and TrkB independent on phospho-CREB immunocontent in the hippocampus. Ardais, AP; Botton, PH; Costa, MS; Mioranzza, S; Moreira, JD; Porciúncula, LO; Souza, DO, 2008)	2.51
"Caffeine treatment (10.0 mM) of aging oocytes prevented the decline in activities associated with both kinases and prevented the acquisition of activation competence by a single activation stimulus."	( Caffeine treatment prevents age-related changes in ovine oocytes and increases cell numbers in blastocysts produced by somatic cell nuclear transfer. Campbell, KH; Lee, JH, 2008)	2.51
"Most caffeine-treated mitotic cells showed misalignment of chromosomes at the metaphase plates, and were arrested at prometaphase."	( Caffeine yields aneuploidy through asymmetrical cell division caused by misalignment of chromosomes. Imoto, I; Inazawa, J; Katsuki, Y; Mizutani, S; Nagasawa, M; Nakada, S; Yokoyama, T, 2008)	2.24
"Caffeine treatment was effective only when associated with ultrasound therapy; the combination resulted in a significant reduction in the thickness of the subcutaneous adipose tissue, as well as damage to the adipocytes, consequently decreasing the number of cells."	( The effect of topical caffeine on the morphology of swine hypodermis as measured by ultrasound. Chorilli, M; Grassi-Kassisse, DM; Leonardi, GR; Pires-de-Campos, MS; Polacow, ML; Spadari-Bratfisch, RC, 2008)	2.1
"Caffeine is a common treatment for apnea of prematurity. "	( Enhancement of the breathing frequency response to hypoxia by neonatal caffeine treatment in adult male rats: the role of testosterone. Bairam, A; Joseph, V; Kinkead, R; Lajeunesse, Y; Montandon, G, 2009)	2.03
"Caffeine-treated mice that showed an area under the curve (AUC) for locomotor activity that was double that of controls were calmed to normal levels by administration of valerena-4,7(11)-diene."	( Evaluation of volatile components from spikenard: valerena-4,7(11)-diene is a highly active sedative compound. Ito, M; Takemoto, H; Yagura, T, 2009)	1.07
"Caffeine-treated rats also had higher catalepsy latency scores compared with control rats (P<0.01, U-test)."	( Long-lasting resistance to haloperidol-induced catalepsy in male rats chronically treated with caffeine. Alvarez-Cervera, FJ; Bata-García, JL; Góngora-Alfaro, JL; Heredia-López, FJ; Moo-Puc, RE; Pineda, JC; Villanueva-Toledo, JR, 2009)	1.29
"Caffeine (10 mg/kg) pretreatment with venlfaxine (5 mg/kg) did not produce any significant effect on locomotor activity, immobility period and oxidative damage as compared to their effect per se."	( Venlafaxine involves nitric oxide modulatory mechanism in experimental model of chronic behavior despair in mice. Garg, R; Gaur, V; Kumar, A; Kumar, P, 2010)	1.08
"Caffeine treatment repressed ERK-mediated c-Fos phosphorylation but evoked p38 MAPK-mediated c-Jun phosphorylation."	( Caffeine induces matrix metalloproteinase-2 (MMP-2) and MMP-9 down-regulation in human leukemia U937 cells via Ca2+/ROS-mediated suppression of ERK/c-fos pathway and activation of p38 MAPK/c-jun pathway. Chang, LS; Liu, WH, 2010)	2.52
"Caffeine and melatonin treatments did not yield robust evidence to recommend their use as single preventive agents."	( Focus on therapy of hypnic headache. Ferrante, E; Lisotto, C; Nappi, G; Rossi, P; Tassorelli, C, 2010)	1.08
"Caffeine treatment of ovine oocytes increases the activity of maturation-promoting factor (MPF) and mitogen-activated protein kinases (MAPKs) and, in somatic cell nuclear transfer (SCNT) embryos, increases the frequency of nuclear envelope breakdown (NEBD) and premature chromosome condensation (PCC). "	( Treatment of ovine oocytes with caffeine increases the accessibility of DNase I to the donor chromatin and reduces apoptosis in somatic cell nuclear transfer embryos. Campbell, KH; Choi, I, 2010)	2.09
"Caffeine treatment for apnea of prematurity correlates with changes in cytokine profile. "	( Correlation between serum caffeine levels and changes in cytokine profile in a cohort of preterm infants. Ahlawat, R; Chavez Valdez, R; Ezell, T; Gauda, EB; Nathan, A; Wills-Karp, M, 2011)	2.11
"Caffeine treatment in 7- and 14-days-old rats decreased ATP hydrolysis when compared to the control group (19% and 60% decrease, respectively), but 21-days-treated rats showed an increase in ATP hydrolysis (39%)."	( Profile of nucleotide catabolism and ectonucleotidase expression from the hippocampi of neonatal rats after caffeine exposure. Bogo, MR; Bonan, CD; Da Silva, RS; Richetti, SK; Tonial, EM, 2012)	1.31
"Caffeine treatment stimulated PKA activity, increased phospho-CREB levels, and decreased phospho-JNK and phospho-ERK expression in the striatum of APPswe mice, all of which are thought to be beneficial changes for brain function."	( Caffeine induces beneficial changes in PKA signaling and JNK and ERK activities in the striatum and cortex of Alzheimer's transgenic mice. Arendash, GW; Burgess, S; Echeverria, V; Patel, S; Zeitlin, R, 2011)	2.53
"Caffeine treatment of 70 μM resulted in significant improvements in PO in maximally and submaximally activated EDL and soleus (P < 0.03 in all cases)."	( The effect of physiological concentrations of caffeine on the power output of maximally and submaximally stimulated mouse EDL (fast) and soleus (slow) muscle. Cox, VM; Duncan, MJ; James, RS; Tallis, J, 2012)	1.36
"Caffeine-treated rats exhibited transient changes: single responses were augmented in P25 if high stimulation intensity was used, paired-pulse and frequency responses were higher in experimental than in control animals at P12, the opposite change was observed in 18- and more markedly in 25-day-old rats."	( Transient changes of cortical interhemispheric responses after repeated caffeine administration in immature rats. Kubová, H; Mareš, P; Tchekalarova, J, 2011)	1.32
"Caffeine treatment (5 mg/kg/day) began when animals were ≈4 months old, and lasted for 6 months."	( Chronic caffeine consumption prevents cognitive decline from young to middle age in rats, and is associated with increased length, branching, and spine density of basal dendrites in CA1 hippocampal neurons. Alvarez-Cervera, FJ; Arankowsky-Sandoval, G; Bata-García, JL; Cabrera-Isidoro, S; Flores, G; Góngora-Alfaro, JL; Heredia-López, F; Juárez-Díaz, I; Vila-Luna, L; Vila-Luna, S; Zapata-Vázquez, RE, 2012)	1.53
"In caffeine-treated oocytes, 6 proteins were identified as up-regulated and 12 proteins were identified as down-regulated."	( Protein profile changes during porcine oocyte aging and effects of caffeine on protein expression patterns. Guo, L; Hou, Y; Jiang, GJ; Miao, DQ; Schatten, H; Sun, QY; Wang, K, 2011)	1.12
"Caffeine-treated embryos showed no defects in vasculogenesis, but revealed dose-dependent (250-350 ppm) developmental defects in intersegmental vessels, dorsal longitudinal anastomotic vessels, and subintestinal vein sprouting."	( Caffeine treatment disturbs the angiogenesis of zebrafish embryos. Chang, CY; Chen, YH; Cheng, CC; Liao, YF; Tsai, JN; Wang, YH; Wen, CC; Yeh, CH, 2012)	2.54
"Caffeine treatment seekers (mean age 41 years, 55% women) consumed an average of 548 mg caffeine per day."	( Characterization of individuals seeking treatment for caffeine dependence. Evatt, DP; Griffiths, RR; Juliano, LM; Richards, BD, 2012)	1.35
"Caffeine treatment reduces the frequency of apnoea of prematurity (AOP) and eliminates the need for mechanical ventilation by acting as a nonspecific inhibitor of adenosine A1 and adenosine 2A receptors. "	( Genetic basis of apnoea of prematurity and caffeine treatment response: role of adenosine receptor polymorphisms: genetic basis of apnoea of prematurity. Duman, N; Kumral, A; Ozkan, H; Tuzun, F; Yesilirmak, DC, 2012)	2.08
"Caffeine treatment substantially reduced i) age-related impairments in the two types of memory in an inhibitory avoidance paradigm, and ii) parallel increases in hippocampal BDNF levels."	( Chronic caffeine prevents changes in inhibitory avoidance memory and hippocampal BDNF immunocontent in middle-aged rats. Ardais, AP; Botton, PH; Costa, MS; Elisabetsky, E; Fioreze, GT; Forte, T; Klaudat, B; Nunes, F; Porciúncula, LO; Sallaberry, C; Souza, DO, 2013)	1.55
"Caffeine-treated chronically hypoxic rats exhibited a decrease in the CSN response to acute hypoxia tests but maintained ventilation compared with chronically hypoxic animals."	( Chronic caffeine intake in adult rat inhibits carotid body sensitization produced by chronic sustained hypoxia but maintains intact chemoreflex output. Conde, SV; Gonzalez, C; Monteiro, EC; Obeso, A; Ribeiro, MJ; Rigual, R, 2012)	1.53
"Caffeine treatment by itself yielded a small increase in mitochondrial function."	( Caffeine increases mitochondrial function and blocks melatonin signaling to mitochondria in Alzheimer's mice and cells. Arendash, GW; Bradshaw, PC; Cao, C; Copes, N; Delic, V; Dragicevic, N; Lin, X; Mamcarz, M; Wang, L, 2012)	2.54
"Caffeine treatment increased the percentage of mitotic tumor cells undergoing apoptosis (lethal mitosis) whereas RW inhibited the increase in interleukin-6 that occurred during the progression of LNCaP tumors from androgen dependence to androgen independence."	( Inhibition of progression of androgen-dependent prostate LNCaP tumors to androgen independence in SCID mice by oral caffeine and voluntary exercise. Conney, AH; Cui, XX; Huang, MT; Lee, MJ; Lin, Y; Liu, Y; Shih, WJ; Wagner, GC; Yang, CS; Zheng, X, 2012)	1.31
"In Caffeine+Cisplatin treated groups, the total body weight, the weight of testes and kidneys and also the histopathological data did not show significant differences."	( Protective effects of subchronic caffeine administration on cisplatin induced urogenital toxicity in male mice. Alian, HA; Bayat, PD; Feizian, M; Ghanbari, A; Khazaei, M; Khazaei, S; Khodaei, A, 2012)	1.17
"In caffeine-treated subjects, the fractional excretion of sodium rose from 1.00+/-0.25% in the control period to 1.47+/-0.18% in the experimental period, while corresponding values on the placebo day were 1.04+/-0.16% and 0.70+/-0.07% respectively."	( Natriuretic effect of caffeine: assessment of segmental sodium reabsorption in humans. Noormohamed, FH; Shirley, DG; Walter, SJ, 2002)	1.14
"The caffeine and coffee treatments increased fasting homocysteine by 0.4 micro mol/L (95% CI: 0.1, 0.7; P = 0.04), or 5%, and by 0.9 micro mol/L (95% CI: 0.6, 1.2; P = 0.0001), or 11%, respectively, compared with placebo."	( Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans. Katan, MB; Pasman, WJ; Urgert, R; Van Vliet, T; Verhoef, P, 2002)	1.14
"Caffeine treatment enhanced feeding of l-dopa-treated mutants but, unexpectedly, it reduced their hyperlocomotion."	( Adenosine receptor blockade reverses hypophagia and enhances locomotor activity of dopamine-deficient mice. Kim, DS; Palmiter, RD, 2003)	1.04
"Caffeine treatment induced a marked, almost total neuroprotection in CA1 and a very limited protection in the hilus of the dentate gyrus, whereas damage in layers III-IV of the piriform cortex was slightly worsened by the treatment. "	( Prolonged low-dose caffeine exposure protects against hippocampal damage but not against the occurrence of epilepsy in the lithium-pilocarpine model in the rat. Ferrandon, A; Koning, E; Leroy, C; Nehlig, A; Rigoulot, MA, 2003)	2.09
"Caffeine treatment showed glutathione depletion and increased lipid peroxidation with higher glutathione S-transferase activity in both B16F10 and B16F1 cell lines. "	( Potentiation of lipid peroxidation in B16F10 and B16F1 melanoma cells by caffeine, a methylxanthine derivative: relationship to intracellular glutathione. Gude, RP; Shukla, V, 2003)	1.99
"A caffeinetreated group was administered 80 mg/kg-body weight by an i.p injection at 1 hour before irradiation."	( Evaluation of caffeine as a radioprotector in whole-body irradiated male mice. Kim, JH; Kim, JK; Yoon, YD, )	1.05
"Caffeine treatment also resulted in increased phosphorylation of calmodulin-dependent protein kinase (CAMK)-II in epitrochlearis muscle."	( Ca2+ and AMPK both mediate stimulation of glucose transport by muscle contractions. Han, DH; Holloszy, JO; Hucker, KA; Wright, DC, 2004)	1.04
"Caffeine treatment augmented A1AR expression on microglia, with ensuing reduction of EAE severity, which was further enhanced by concomitant treatment with the A1AR agonist, adenosine amine congener."	( A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis. Henry, S; Noorbakhsh, F; Power, C; Schnermann, J; Tsutsui, S; Warren, K; Winston, BW; Yong, VW, 2004)	1.04
"Caffeine-treated melanophores displayed dispersed melanosomes in cells with less serrated edges and reduced FD and complexity."	( Characterization of melanophore morphology by fractal dimension analysis. Anton Hough, R; Carl Freeman, D; Kimler, VA; Langer, RM; Marks, CR; Montante, JM; Ollie, CD; Taylor, JD; Tracy-Bee, M, 2004)	1.04
"Caffeine treatment significantly increased cAMP levels in the oocytes after 24 h of culture, while both Cdc2 kinase and MAP kinase activation were inhibited in the oocytes."	( Effect of caffeine on meiotic maturation of porcine oocytes. Kren, R; Miyano, T; Ogushi, S, 2004)	1.45
"Caffeine pretreatment did not alter nicotine discrimination and self-administration."	( The influence of caffeine on nicotine's discriminative stimulus, subjective, and reinforcing effects. Blakesley-Ball, R; Fonte, C; Perkins, KA; Stolinski, A; Wilson, AS, 2005)	1.39
"(1) Caffeine treatment produced a dose-dependent attenuation of MPTP-induced striatal dopamine loss in both young and retired breeder (RB) male, but not female, mice."	( Estrogen prevents neuroprotection by caffeine in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Ascherio, A; Brown-Jermyn, D; Chen, JF; Dluzen, DE; Schwarzschild, MA; Xu, K; Xu, Y, 2006)	1.09
"The caffeine treatment suppressed the radiation-induced activation of ATM kinase, suppressed the activation of Chk2 kinase and inhibited the accumulation of cells in G2 phase."	( Radiosensitization of tumor cells by modulation of ATM kinase. Choi, EK; Griffin, RJ; Ji, IM; Kim, JS; Kook, YH; Lee, DS; Lee, SR; Lim, BU; Park, HJ; Song, CW, 2006)	0.81
"Caffeine treatment increased epinephrine, fatty acids, lactate and norepinephrine at different times during test session and led to insulin-resistance. "	( Metabolic effects of caffeine ingestion and physical work in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study. Jensen, MB; Madsen, MR; Norager, CB; Weimann, A, 2006)	2.1
"Caffeine-treated rats showed hyperalgesia in hot-plate test, less anxiety than controls in the elevated plus-maze and dark-light transition, and impairment in step-through avoidance learning test. "	( Hyperalgesia, low-anxiety, and impairment of avoidance learning in neonatal caffeine-treated rats. Chen, HH; Pan, HZ, 2007)	2.01
"Caffeine treatment is widely used in nursing care to reduce the risk of apnoea in premature neonates. "	( Sequential updating of a new dynamic pharmacokinetic model for caffeine in premature neonates. Amzal, B; Bach, V; Bois, FY; Chardon, K; Micallef, S; Tourneux, P, 2007)	2.02
"Both caffeine treatment and electrical stimulation significantly increased FA uptake and oxidation."	( Evidence for the involvement of CaMKII and AMPK in Ca2+-dependent signaling pathways regulating FA uptake and oxidation in contracting rodent muscle. Raney, MA; Turcotte, LP, 2008)	0.8
"Caffeine-treated NTs induced premature chromosome condensation at a high rate (P<0.05), whereas most vanadate-treated NTs formed a pronucleus-like structure."	( Control of nuclear remodelling and subsequent in vitro development and methylation status of porcine nuclear transfer embryos. Cheong, HT; Kwon, DJ; Park, CK; Yang, BK, 2008)	1.07
"Four caffeine-treated rats had histologic evidence of acute myocardial infarction which was not found in any of the other rats."	( Cardiovascular lesions in Sprague-Dawley rats induced by long-term treatment with caffeine. Johansson, S, 1981)	0.94
"Caffeine treatment had no effect on trichloroethylene blood concentration, but significantly decreased trichloroethanol blood levels after 45 and 60 minutes of exposure to trichloroethylene."	( Epinephrine-induced cardiac arrhythmias in rabbits exposed to trichloroethylene: potentiation by caffeine. Carlson, GP; White, JF, )	1.07
"Caffeine treatment did not effect CSF beta-endorphin levels or the release of beta-endorphin from hemipituitaries incubated in vitro."	( Caffeine stimulates beta-endorphin release in blood but not in cerebrospinal fluid. Arnold, MA; Carr, DB; Martin, JB; Pian, MC; Togasaki, DM, 1982)	2.43
"Caffeine treatment of rats prior to and during carcinogen treatment did not significantly affect mammary carcinoma incidence."	( Caffeine (1,3,7-trimethylxanthine), a temperature promoter of DMBA-induced rat mammary gland carcinogenesis. DeHoog, JV; Scieszka, KM; Senn, ER; Welsch, CW, 1983)	2.43
"The caffeine treated subjects differed from the other groups by increased regularity of letter cancellation performance, as indicated by decreases in intraindividual variance."	( The effects of caffeine on physiological functions and mental performance. Bättig, K; Buzzi, R; Feierabend, JM; Martin, JR, 1984)	1.1
"Caffeine treatment (100 mg/kg for 3 days) increased relative liver weight in female guinea-pigs and decreased it in chicks and female mice, and decreased microsomal protein content in male mice, female guinea-pigs and young rats, and increased it in chicks."	( In vivo and in vitro effects of caffeine on hepatic mixed-function oxidases in rodents and chicks. Govindwar, SP; Kachole, MS; Pawar, SS, 1984)	1.27
"Caffeine treatment at a daily dose of 1 g per day for one week had no apparent effect on the absorption or disposition of quinidine after a single 300-mg oral dose of quinidine sulfate in healthy men."	( Effect of caffeine on the oral absorption and disposition of quinidine. Meyers, DG; Ueda, CT; Wulf, BG; Zeller, FP, )	1.26
"Caffeine pretreatment was studied for its effects on d-amphetamine-induced locomotor activity. "	( Caffeine pretreatment: enhancement and attenuation of d-amphetamine-induced activity. Keller, GE; White, BC, 1984)	3.15
"Caffeine pretreatment attenuated amphetamine activity in the rats without producing a horizontal shift in the dose-response curve."	( Caffeine reduces amphetamine-induced activity in asymmetrical interaction. Crumbie, PM; Harkins, D; Haswell, KL; Kassab, CD; White, BC, 1984)	2.43
"Caffeine treatment of frozen-thawed human spermatozoa also increased the number of spermatozoa penetrating cervical mucus in unit time, by increasing the frequency rather than the success of collisions between spermatozoa and the cervical mucus interface."	( Influence of caffeine on movement characteristics, fertilizing capacity and ability to penetrate cervical mucus of human spermatozoa. Aitken, RJ; Best, F; Richardson, DW; Schats, R; Simm, G, 1983)	1.36
"When caffeine-treated horses were given fentanyl, the locomotor response to fentanyl was enhanced."	( Pharmacology, pharmacokinetics, and behavioral effects of caffeine in horses. Greene, EW; Tobin, T; Woods, WE, 1983)	0.97
"In caffeine-treated sympathetic ganglion cells, however, Ca2+ released from an intracellular Ca2+ reservoir site analogous to the sarcoplasmic reticulum (SR) of the muscle (see ref."	( Oscillation of [Ca2+]i-linked K+ conductance in bullfrog sympathetic ganglion cell is sensitive to intracellular anions. Koketsu, K; Kuba, K; Morita, K, 1980)	0.78
"In caffeine-treated muscle fibres, electrically produced depolarization could initiate or increase the frequency of sarcomeric oscillations, and electrical hyperpolarization diminishes the frequency or stops sarcomeric oscillations."	( Action of caffeine in excitation-contraction coupling of frog skeletal muscle fibres. Kumbaraci, NM; Nastuk, WL, 1982)	1.18
"Caffeine-treated nuclei had lower protein contents than untreated nuclei, yet they completed a cell cycle and entered mitosis; this suggests that nonessential proteins were no longer present."	( Differences in protein content of sister nuclei: evidence from binucleate and mononucleate cells. Armstrong, SW; Davidson, D, 1982)	0.99
"With caffeine treatment, about 73% of neuron-like cells were c-fos labelled in the lateral striatum, but labelling was much less pronounced in the medial part or in the accumbens."	( Differences in the regional and cellular localization of c-fos messenger RNA induced by amphetamine, cocaine and caffeine in the rat. Fredholm, BB; Johansson, B; Lindström, K, 1994)	0.95
"Caffeine-treated cells that pass through S phase are incapable of recovery."	( Inhibitory effect of caffeine on potentially lethal damage repair in cisplatin-treated human osteosarcoma cells. Matsunaga, T; Mori, T; Nikaido, O; Tomita, K; Tsuchiya, H; Yasutake, H, )	1.17
"Caffeine treatment reduced intracellular cAMP."	( Hemocyte adhesion in the California mussel (Mytilus californianus): regulation by adenosine. Bayne, CJ; Chen, JH, 1995)	1.01
"Caffeine-treated rats were cross-tolerant to the locomotor stimulant effect of these selective dopamine D1 and D2 receptor agonist."	( Caffeine cross-tolerance to selective dopamine D1 and D2 receptor agonists but not to their synergistic interaction. Garrett, BE; Holtzman, SG, 1994)	2.45
"Both caffeine and NaCl treatments exerted growth retardation effects, the suppression being stronger with caffeine than NaCl, and animals in group 1 (NaCl plus caffeine) showing the lowest body weight."	( Effects of caffeine on glandular stomach carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride. Furukawa, F; Hasegawa, T; Ikezaki, S; Imazawa, T; Nishikawa, A; Takahashi, M, 1995)	1.14
"Caffeine post-treatment decreased notably the mutation frequency of EMS treatment; when concentrations of EMS were very high (1.5% and 1.8%), mutation frequencies of EDTA post-treatment were still 5.0% and 4.88%, but no mutants were found in EMS treatment or plus caffeine post-treatment."	( Effects of caffeine or EDTA post-treatment on EMS mutagenesis in soybean. Deng, X; Geng, Y; Gu, A; Lu, Z; Zhu, B, 1995)	1.4
"Caffeine pretreatment followed by AA-PDGF stimulation resulted in Ca2+n oscillations very similar to those produced by BB-PDGF alone."	( Isoform-specific induction of nuclear free calcium oscillations by platelet-derived growth factor. Diliberto, PA; Herman, B; Krishna, S; Kwon, S, 1994)	1.01
"Caffeine treatment of irradiated HeLa cells also resulted in an elevation in the levels of cyclin B1 message."	( Increased expression of cyclin B1 mRNA coincides with diminished G2-phase arrest in irradiated HeLa cells treated with staurosporine or caffeine. Bernhard, EJ; Maity, A; McKenna, WG; Muschel, RJ, 1994)	1.21
"Caffeine treatment showed no effect on the food intake, but decreased the body fat content significantly in obese mice."	( Effect of caffeine on the levels of brain serotonin and catecholamine in the genetically obese mice. Chen, MD; Ho, LT; Lin, PY; Lin, WH; Song, YM, 1994)	1.41
"Caffeine treatment significantly reduced the kainate-induced intracellular Ca2+ response."	( Kainate elicits elevated nuclear calcium signals in retinal neurons via calcium-induced calcium release. Chen, B; Kocsis, JD; Pourcho, R; Rand, MN; Waxman, SG, 1993)	1.01
"Caffeine pretreatment during 50 min of ischemia, though, resulted in deterioration of both energy charge and cardiac function."	( Effects of caffeine on ischemia-reperfusion injury in isolated rat hearts. Asayama, J; Inoue, D; Inoue, M; Matsumoto, T; Miyazaki, H; Nakagawa, M; Ohta, B; Sakai, R; Tatsumi, T; Yamahara, Y, 1993)	1.4
"Caffeine pretreatment (200 mg), which resulted in intradialytic plasma caffeine levels of about 4 micrograms/mL at time of food ingestion, had no effect on food-associated reductions in blood pressure or SVRI."	( Hemodynamic effects of intradialytic food ingestion and the effects of caffeine. Barakat, MM; Daugirdas, JT; Ing, TS; Lau, AH; Nawab, ZM; Yu, AW, 1993)	1.24
"Caffeine pretreatment was also observed to eliminate nicotinic responses but not elevated extracellular K(+)-induced responses, suggesting that caffeine blocks nicotinic receptor-channels."	( Effects of caffeine on cholinergic agonist- and K(+)-induced cytosolic Ca++ signals and secretion in porcine adrenal chromaffin cells. Forsberg, EJ; Xu, Y, 1993)	1.4
"Caffeine treatment at 20 degrees C resulted in a selective and reversible translocation of the pre- and cis-Golgi marker protein (p58) to the periphery of the cell."	( Effect of caffeine and reduced temperature (20 degrees C) on the organization of the pre-Golgi and the Golgi stack membranes. Jäntti, J; Kuismanen, E, 1993)	1.41
"Caffeine treatment increased the number of A1 receptors in the CA3 subfield of the hippocampus from 337 to 393 fmol/mg with no change in KD (0.692 vs."	( Effect of long term caffeine treatment on A1 and A2 adenosine receptor binding and on mRNA levels in rat brain. Ahlberg, S; Brené, S; Fredholm, BB; Johansson, B; Lindefors, N; Persson, H; van der Ploeg, I, 1993)	1.33
"Caffeine treatment may have some non-adenosine A1 receptor-mediated actions, because it slightly (30%) augmented protein kinase A activity."	( Upregulated renal adenosine A1 receptors augment PKC and glucose transport but inhibit proliferation. Chalfant, CE; Cooper, DR; Coulson, R; Olsson, RA; Proch, PS, 1996)	1.02
"Caffeine treatment (1 g/l, but not 0.1 or 0.3 g/l) tended to increase [3H]CHA binding to the CA3 subfield of the hippocampus, but in no other region studied."	( A1 and A2A adenosine receptors and A1 mRNA in mouse brain: effect of long-term caffeine treatment. Fredholm, BB; Georgiev, V; Johansson, B; Lindström, K, 1997)	1.25
"Caffeine treatment, which increased the frequency of the oscillations, had no effect on the number or the size of the Ca2+ steps, but it reduced the time needed for each step to reach its maximum height."	( Kinetics of calcium steps underlying calcium oscillations in melanotrope cells of Xenopus laevis. Jenks, BG; Koopman, WJ; Roubos, EW; Scheenen, WJ, 1997)	1.02
"Caffeine treatment produced a more pronounced decrease in the AMF (61%, P < 0.01) than in the NLF (25%, P < 0.01)."	( Inhibition of melanoma pulmonary metastasis by methylxanthines due to decreased invasion and proliferation. Abbruzzese, A; Autuori-Pezzoli, V; Beninati, S; Cardinali, M; Kleinman, HK; Lentini, A; Mattioli, P; Nicolini, L; Pietrini, A, 1998)	1.02
"Caffeine treatment restored these activities after either of the treatments."	( The G2 block induced by DNA damage: a caffeine-resistant component independent of Cdc25C, MPM-2 phosphorylation, and H1 kinase activity. Barratt, RA; Kao, G; Kuang, J; McKenna, WG; Muschel, RJ, 1998)	1.29
"Caffeine-ephedrine pretreatments failed to show any significant change in the administration of the maintenance dose of cocaine except at the highest combination dose tested."	( Reinforcing effects of caffeine, ephedrine, and their binary combination in rats. Baird, TJ; Briscoe, RJ; Gauvin, DV; Holloway, FA; Vallett, M; Vanecek, SA, 1998)	1.33
"Caffeine treatment for 20 weeks had no effects on blood pressure, heart rate, or vascular resistance in four examined vascular beds (abdominal aorta and renal, carotid, and mesenteric arteries)."	( Effects of long-term caffeine consumption on renal function in spontaneously hypertensive heart failure prone rats. Jackson, EK; Tofovic, SP, 1999)	1.34
"Caffeine treatment or removal of MEK1/2 inhibitors from cells 6 h after irradiation reduced the proportion of cells present in G(2)/M phase at 24 h and abolished the ability of MAPK inhibition to potentiate radiation-induced apoptosis."	( Roles for basal and stimulated p21(Cip-1/WAF1/MDA6) expression and mitogen-activated protein kinase signaling in radiation-induced cell cycle checkpoint control in carcinoma cells. Carter, S; Dent, P; Fisher, PB; Park, JS; Reardon, DB; Schmidt-Ullrich, R, 1999)	1.02
"Caffeine treatment sensitizes neurons expressing mutant PS1 to apoptosis induced by amyloid beta-peptide, a neurotic peptide linked to the pathogenesis of AD."	( Presenilin-1 mutations increase levels of ryanodine receptors and calcium release in PC12 cells and cortical neurons. Chan, SL; Geiger, JD; Holden, CP; Mattson, MP; Mayne, M, 2000)	1.03
"Caffeine treatment given at the time of operation might prevent these episodes."	( Postoperative caffeine for preventing apnea in preterm infants. Henderson-Smart, DJ; Steer, P, 2000)	1.39
"Caffeine treatment could bypass the G2/M block in DLKP-SQ cells."	( Altered cell cycle response of drug-resistant lung carcinoma cells to doxorubicin. Clynes, M; Coyle, S; Heenan, M; O'Loughlin, C, 2000)	1.03
"Caffeine was treated orally each day at either 2.5 mg (low dose) or 10 mg (high dose) per 100 g body weight for a period of 17 or 32 days."	( Effects of long-term treatment with caffeine on the ultrastructure of the golden hamster parathyroid gland and tibia. Chen, H; Emura, S; Hayakawa, D; Jamali, M; Ozawa, Y; Shoumura, S; Taguchi, H; Yano, R, 2000)	1.3
"Caffeine treatment had no significant effect on adenosine A1 receptors or on A1 receptor mRNA."	( Maternal caffeine intake has minor effects on adenosine receptor ontogeny in the rat brain. Adén, U; Fredholm, BB; Herlenius, E; Tang, LQ, 2000)	1.45
"Caffeine-pretreated cells exhibited a rundown in the secretory response that was similar to that produced by thapsigargin."	( Rundown of secretion after depletion of intracellular calcium stores in bovine adrenal chromaffin cells. Fox, AP; Pan, CY, 2000)	1.03
"Caffeine treatment for 1 week (10 mg/kg, i.p., twice a day) was followed by unchanged pump function of the isolated heart, but reduced maximal left ventricular (LV) systolic pressure by 14% (p < 0.05)."	( Effects of prolonged caffeine consumption on cardiac contractile function in rats. Kapelko, VI; Lakomkin, VL; Pisarenko, OI; Studneva, IM, 2000)	1.35
"Caffeine as first-line treatment demonstrated similar efficacy to theophylline or aminophylline (theophylline ethylenediamine) in 4 small randomised studies."	( Caffeine citrate: a review of its use in apnoea of prematurity. Comer, AM; Figgitt, DP; Perry, CM, 2001)	2.47
"Caffeine treatment significantly (p < 0.05) reduced body weight, food, and fluid consumption and improved insulin sensitivity (fasting insulin 129.6+/-8.1 vs 97.5+/-3.6 microIU/mL; fed insulin 146.3+/-8.5 vs 110.6+/-3.4 microIU/mL; fasting glucose 138.7+/-13.4 vs 145+/-8.0 mg/dL; fed glucose 373+/-19.4 vs 283.3+/-19.6 mg/dL, Cont vs Caff, respectively)."	( Renal and metabolic effects of caffeine in obese (fa/fa(cp)), diabetic, hypertensive ZSF1 rats. Bastacky, SI; Jackson, EK; Kusaka, H; Tofovic, SP, 2001)	1.32
"The Caffeine treated metastatic tumour bearing animals significantly (p<0.001) inhibited lung tumour nodules."	( Effect of Caffeine, a xanthine derivative, in the inhibition of experimental lung metastasis induced by B16F10 melanoma cells. Gude, RP; Menon, LG; Rao, SG, 2001)	1.19
"Caffeine treatment caused the G-actin tip-focused gradient to disappear, and F-actin to extend into the pollen tube tip."	( Circular F-actin bundles and a G-actin gradient in pollen and pollen tubes of Lilium davidii. Huang, BQ; Li, Y; Liu, YM; Yen, LF; Zee, SY, 2001)	1.03
"In caffeine-treated HEK cultures, CMV replicated better than in untreated cultures in which virus growth was transitory and decreased after 10 days of incubation."	( Effect of caffeine on the replication of nonirradiated and ultraviolet-irradiated cytomegalovirus. Fogel, M; Rapp, F; Yamanishi, K, 1978)	1.17
"On caffeine post-treatment potentiation of the MC-induced aberration frequency occurred in all the cell lines."	( The influence of caffeine on the mitomycin C-induced chromosome aberration frequency in normal human and xeroderma pigmentosum cells. Hartley-Asp, B, 1978)	1.11
"Caffeine treatment before UV2, with or without UV1, significantly increased the mutation frequencies."	( Modification of UV-induced mutation frequencies in Chinese hamster cells by dose fractionation, cycloheximide and caffeine treatments. Chang, CC; D'Ambrosio, SM; Schultz, R; Setlow, RB; Trosko, JE, 1978)	1.19
"In caffeine-treated cells soon after the transfer to the sporulation medium a significant increase in RNase activity was observed; in control cells the rise of RNase activity was less and started after a lag period of 5 h."	( Promotion of sporulation by caffeine pretreatment in Saccharomyces cerevisiae. II. Changes in ribonuclease activity during sporulation. Tsuboi, M; Yanagishima, N, 1976)	1.06
"Caffeine treatment led to an enhancement of the frequencies of sex-chromosome loss and a decrease in those of rearrangements."	( The effect of caffeine on repair systems in oocytes of Drosophila melanogaster. Mendelson, D, 1976)	1.34
"This caffeine treatment reduced the surviving fraction (assayed by colony formation) of the irradiated population, but did not significantly reduce the colony-forming ability of unirradiated control cells."	( Potentiation by caffeine of ultraviolet-light damage in cultured human cells. Schroy, CB; Todd, P, 1975)	1.06
"Pure caffeine treated under conditions of the tea preparation formed caffeidine and caffeidine acid."	( Caffeine-derived N-nitroso compounds--I: Nitrosatable precursors from caffeine and their potential relevance in the etiology of oesophageal and gastric cancers in Kashmir, India. Kumar, R; Mende, P; Preussmann, R; Siddiqi, M; Spiegelhalder, B; Wacker, CD, 1992)	2.18
"The caffeine post-treatment (5 mg/kg and 15 mg body weight) was given in the form of an intraperitoneal injection to the mice immediately following whole-body gamma-irradiation."	( Radioprotection by caffeine pre- and post-treatment in the bone marrow chromosomes of mice given whole-body gamma-irradiation. Farooqi, Z; Kesavan, PC, 1992)	1.09
"Caffeine treatment of ryanodine-injected eggs or ryanodine injection of caffeine-treated eggs stimulated a Ca2+ release significantly larger than the release by either drug independently."	( Synergistic release of calcium in sea urchin eggs by caffeine and ryanodine. Buck, WR; Rakow, TL; Shen, SS, 1992)	1.25
"Caffeine pretreatment significantly increased the incidence of overt seizures induced by either cocaine or amphetamine."	( Potentiation of cocaine and d-amphetamine toxicity with caffeine. Albertson, TE; Derlet, RW; Tseng, JC, 1992)	1.25
"Caffeine treatment significantly (P less than 0.05 to P less than 0.001) reduced the incidence of benign mammary fibroadenomas in the 55 day old virgin rat model (P less than 0.01), in the 53 day old estrogen treated ovariectomized virgin rat model (P less than 0.05 to P less than 0.001) and in the 135 day old virgin rat model (P less than 0.05)."	( Caffeine inhibits development of benign mammary gland tumors in carcinogen-treated female Sprague-Dawley rats. Rao, AR; Welsch, CW; Wolfrom, DM, 1991)	2.45
"Caffeine treatment blocks both the G1 arrest and the induction of p53 protein after gamma-irradiation, thus suggesting that blocking the induction of p53 protein may contribute to the previously observed effects of caffeine on cell cycle changes after DNA damage."	( Participation of p53 protein in the cellular response to DNA damage. Craig, RW; Kastan, MB; Onyekwere, O; Sidransky, D; Vogelstein, B, 1991)	1
"Caffeine treatments alone increase the frequencies of chromatid breakage and decrease the average G2 duration in control and X-ray-irradiated lymphocytes (40 R)."	( Effects of caffeine and cycloheximide during G2 prophase in control and X-ray-irradiated human lymphocytes. López-Sáez, JF; Pincheira, J, 1991)	1.39
"Caffeine treatment significantly (P less than 0.05) reduced the mean number of mammary tumors per mouse and significantly (P less than 0.05) increased the mean latency period of mammary tumor appearance."	( Inhibition by caffeine of ovarian hormone-induced mammary gland tumorigenesis in female GR mice. VanderPloeg, LC; Welsch, CW, 1991)	1.36
"Caffeine treatment at the dose 10 mg/kg b."	( Validation of aversion towards open space and height as a measure of anxiety in the genetically based animal model of depression. Golda, V; Petr, R, 1990)	1
"Caffeine treatment under anaerobic conditions caused direct DNA strand breakage in B."	( Induction and repair of DNA strand breaks in Bacteroides fragilis. Abratt, VR; Peak, JG; Peak, MJ; Santangelo, JD; Woods, DR, 1990)	1
"The caffeine-modified ECT treatments were well tolerated and were associated with no clinically significant adverse cardiovascular effects."	( Caffeine-modified electroconvulsive therapy in depressed patients with medical illness. Coffey, CE; Lurie, SN, 1990)	2.2
"Caffeine, used for treatment of idiopathic apnea in preterm infants, may have a vasoconstrictive effect on cerebral vessels. "	( Does caffeine affect cerebral blood flow in the preterm infant? Baan, J; Ruys, JH; Stijnen, T; Van Bel, F; Van de Bor, M, 1989)	2.23
"Caffeine-treated and control mice of the F1 generation were then cross-mated."	( Preliminary indications that functional effects of fetal caffeine exposure can be expressed in a second generation. Sinton, CM, )	1.1
"Caffeine-treatment increased the number of high affinity binding sites for [3H]-CHA by 64% over the control values."	( Chronic caffeine treatment reduces caffeine but not adenosine effects on cortical acetylcholine release. Corradetti, R; Pedata, F; Pepeu, G; Vannucchi, MG, 1986)	1.43
"With caffeine pretreatment, nifedipine decreased blood pressure significantly more than with placebo pretreatment."	( Cardiovascular effects of caffeine and nifedipine. Myers, MG; van Nguyen, P, 1988)	1.03
"Caffeine pretreatment did not enhance the rapid-pressor response to acute intravenous infusions of AII."	( Caffeine enhances the slow-pressor response to angiotensin II in rats. Evidence for a caffeine-angiotensin II interaction with the sympathetic nervous system. Branch, RA; Holycross, B; Jackson, EK; Li, P; Ohnishi, A, 1987)	2.44
"The caffeine-treated calvaria were similar morphologically at all levels when compared to their littermate controls."	( Caffeine does not cause in vitro calcium loss from neonatal mouse calvaria. Bergman, EA; Massey, LK; Newbrey, JW, 1988)	2.2
"Caffeine treatment significantly increased the number of A1 adenosine receptors as determined with the A1 adenosine receptor antagonist radioligand [3H]xanthine amine congener (XAC)."	( Multiple components of the A1 adenosine receptor-adenylate cyclase system are regulated in rat cerebral cortex by chronic caffeine ingestion. Bumgarner, JR; Jacobson, KA; Ramkumar, V; Stiles, GL, 1988)	1.2
"Caffeine treatment causes rapid killing immediately after irradiation irrespective of cell age, while HeLa is refractory in S phase and highly sensitive in G2."	( Caffeine-induced modulation of the lethal action of X rays on Chinese hamster V79 cells. Beetham, KL; Labanowska, J; Tolmach, LJ, 1988)	2.44
"In caffeine-treated preparations, peaks of light and tension were augmented by application of procaine (0.5-1.0 mM)."	( Effects of caffeine on intracellular calcium concentrations in frog skeletal muscle fibres. Konishi, M; Kurihara, S, 1987)	1.18
"Caffeine treatment potentiated the BCNU-induced accumulation of cells in late-S-G2-M phase of the cell cycle."	( Effect of caffeine on cytotoxicity and sister chromatid exchange induction in sensitive and resistant rat brain tumor cells treated with 1,3-bis(2-chloroethyl)-1-nitrosourea. Aida, T; Bodell, WJ, 1987)	1.4
"In caffeine-treated rats, the administration of diazepam induced the same effects of brain energy metabolism as in saline-treated rats."	( Caffeine-diazepam interaction and local cerebral glucose utilization in the conscious rat. Boyet, S; Daval, JL; Nehlig, A; Pereira de Vasconcelos, A, 1987)	2.23
"The caffeine post-treatments were, however, more effective in potentiating PS-induced growth damage and caused an additive effect on the frequency of chlorophyll mutations."	( Caffeine potentiation of propane sultone mutagenesis in barley. Kaul, BL; Singh, C, 1985)	2.19
"In caffeine-treated cells these regions were found to be somewhat smaller than but of comparable size with those in untreated cells; this is consistent with the DNA being synthesized in smaller units and argues against the presence of small gaps in the daughter strands."	( Effect of caffeine on DNA synthesis in mammalian cells. Lehmann, AR, 1972)	1.17
"Pretreatment with caffeine to diabetic rats, resulted in improvement of structural changes and decrease in cytokine levels and immuno-markers, expression, and this was in a dose-dependent manner."	( Caffeine protects against hippocampal alterations in type 2 diabetic rats via modulation of gliosis, inflammation and apoptosis. Al-Mahameed, AE; Fadel, R; Fatima, A; Jaradat, A; Nasr El-Din, WA; Othman, MA; Rashid, A; Tayem, Y, 2023)	2.68
"Treatment with caffeine significantly attenuated changes in hyperoxia-induced cell death and apoptosis-associated factors. "	( Prevention of Oxygen-Induced Inflammatory Lung Injury by Caffeine in Neonatal Rats. Bendix, I; Bührer, C; Endesfelder, S; Schmitz, T; Strauß, E, 2020)	1.16
"Treatment with caffeine has reduced intra-partum mortality and/or improved metabolic indicators in other species following hypoxia."	( Maternal caffeine administration to ewes does not affect perinatal lamb survival. Doran, GS; Edwards, SH; Friend, MA; Robertson, SM, 2021)	1.38
"Co-treatment with caffeine significantly decreased these upregulations at all time points investigated, while caffeine without phenobarbital resulted in increased expression of TNFα, IL-1β, and IL-18, but not IFNγ at 6 h."	( Caffeine Protects Against Anticonvulsant-Induced Neurotoxicity in the Developing Rat Brain. Bendix, I; Bührer, C; Endesfelder, S; Schiller, C; Sifringer, M; Weichelt, U, 2017)	2.22
"Treatment with caffeine increased 3β-HSD and 17β-HSD as well as testosterone levels."	( Caffeine improves sperm quality, modulates steroidogenic enzyme activities, restore testosterone levels and prevent oxidative damage in testicular and epididymal tissues of scopolamine-induced rat model of amnesia. Akomolafe, SF; Oboh, G; Ogunsuyi, OB; Olasehinde, TA; Oyeleye, SI, 2019)	2.3
"Treatment with caffeine for 4 weeks decreased blood pressure, serum fasting glucose, insulin, homeostatic model assessment-insulin resistance, and triglyceride levels and increased the serum direct high-density lipoprotein level in fructose-fed rats but not in control rats."	( Caffeine intake improves fructose-induced hypertension and insulin resistance by enhancing central insulin signaling. Chen, BR; Cheng, PW; Cheng, WH; Ho, WY; Liou, JC; Liu, CP; Lu, PJ; Sun, GC; Tseng, CJ; Yeh, TC, 2014)	2.18
"Eyes treated with caffeine reacted with quick dilatation after tropicamide application."	( Topically applied caffeine induces miosis in the ketamine/xylazine anesthetized rat. Kronschläger, M; Meyer, LM; Söderberg, P; Talebizadeh, N; Yu, Z, 2014)	1.06
"Treatment with caffeine also decreased the need for a conservative supplementary therapeutic option.Treatment with gabapentin resulted in better visual analogue scale (VAS) scores after one, two, three and four days when compared with placebo and also when compared with ergotamine plus caffeine at two, three and four days."	( Drug therapy for treating post-dural puncture headache. Basurto Ona, X; Bonfill Cosp, X; Osorio, D, 2015)	0.76
"Pretreatment with caffeine (100 nM and 10 μM) sensitized SH-SY5Y cells to doxorubicin-induced toxicity and increased apoptosis and sensitized PC3 cells to gemcitabine-induced toxicity."	( Modulation of chemotherapy-induced cytotoxicity in SH-SY5Y neuroblastoma cells by caffeine and chlorogenic acid. Anoopkumar-Dukie, S; Arora, D; Desbrow, B; Grant, GD; Hall, S; Hong, Y; Lai, R, 2017)	1
"Co-treatment with caffeine and TAA restored normal liver structure and function."	( Caffeine intake decreases oxidative stress and inflammatory biomarkers in experimental liver diseases induced by thioacetamide: Biochemical and histological study. Amer, MG; Mazen, NF; Mohamed, AM, 2017)	2.22
"Treatment with caffeine for 7 to 10 days in a mouse-model improved endothelial repair after denudation of the carotid artery."	( Caffeine enhances endothelial repair by an AMPK-dependent mechanism. Dimmeler, S; Fichtlscherer, S; Fisslthaler, B; Haendeler, J; Liehn, EA; Popp, R; Spyridopoulos, I; Toennes, SW; Trepels, T; Weber, C; Zeiher, AM; Zernecke, A, 2008)	2.13
"Pretreatment with caffeine, nicotinic acid or non-substituted pyrazinoic acid activated the LPS/D-GalN induced elevation of plasma IL-10 levels at 1 and 2 h, although there were no statistically significant differences in IL-10 levels between control and nicotinic acid or non-substituted pyrazinoic acid treated rats."	( Protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine induced acute liver injury in rats. Akashi, I; Hirano, T; Kagami, K; Oka, K, 2009)	0.68
"Treatment with caffeine significantly increased locomotion reduced by haloperidol, but not at all doses tested."	( Adenosine antagonists reverse the cataleptic effects of haloperidol: implications for the treatment of Parkinson's disease. Goode, T; Harris, A; Trevitt, J; Vallance, C, 2009)	0.69
"Treatment with caffeine significantly attenuated the elevated serum aminotransferase enzymes and reduced the severe extent of hepatic cell damage, steatosis and the immigration of inflammatory cells. "	( Caffeine protects against alcoholic liver injury by attenuating inflammatory response and oxidative stress. Chen, Z; Huang, C; Li, J; Liu, H; Lv, X; Zhang, L; Zhu, P, 2010)	2.16
"Pretreatment with caffeine, theophylline or aminophylline (xanthines) prolongs the duration of ECT seizures but has not been clearly shown in controlled trials to increase efficacy."	( Augmentation strategies in electroconvulsive therapy. Loo, C; MacPherson, R; Simpson, B, 2010)	0.68
"Pretreatment with caffeine increased UVB-induced apoptosis in HaCaT cells."	( Caffeine promotes ultraviolet B-induced apoptosis in human keratinocytes without complete DNA repair. Han, W; He, YY; Ming, M, 2011)	2.14
"Treatment with caffeine also decreased the need for a conservative supplementary therapeutic option."	( Drug therapy for treating post-dural puncture headache. Basurto Ona, X; Bonfill Cosp, X; Martínez García, L; Solà, I, 2011)	0.71
"The treatment with caffeine in the rats fed the high-carbohydrate, high-fat diet decreased body fat and systolic blood pressure, improved glucose tolerance and insulin sensitivity, and attenuated cardiovascular and hepatic abnormalities, although the plasma lipid concentrations were further increased."	( Caffeine attenuates metabolic syndrome in diet-induced obese rats. Brown, L; Kauter, K; Panchal, SK; Ward, LC; Wong, WY, 2012)	2.14
"Pretreatment with caffeine augmented the inhibitory effect of halothane."	( Inhibitory effect of caffeine on C-fibre-evoked excitation in the rat spinal dorsal horn recorded under Ca2+-free condition: an interaction with halothane. Asai, T; Ikeda, H; Kusudo, K; Murase, K; Takenoshita, M, 2003)	0.96
"Treatment with caffeine, quercetin and alizarin at doses of 200, 9 and 9 microg/ml respectively, in drinking water enhanced the exhalation of 14CO2, one of the major end products of NDEA metabolism."	( Caffeine, quercetin and alizarin stimulate the exhalation of metabolic products of [14C]-N-nitrosodiethylamine in mice. Bhardwaj, A; Khanduja, KL; Sangari, RK, 2002)	2.1
"Pretreatment with caffeine suppressed cell proliferation in a dose-dependent manner 36 h after addition of fetal bovine serum as a cell growth stimulator."	( Caffeine inhibits cell proliferation by G0/G1 phase arrest in JB6 cells. Bode, AM; Dong, Z; Hashimoto, T; He, Z; Ma, WY; Schmid, PC; Yang, CS, 2004)	2.09
"Treatment with caffeine significantly increased the number of sperm that bound tightly to the zona pellucida as compared with controls (42 +/- 9 and 13 +/- 3 sperm/zona, respectively; P < or = 0.01)."	( Macaque sperm release ESP13.2 and PSP94 during capacitation: the absence of ESP13.2 is linked to sperm-zona recognition and binding. Cherr, GN; Overstreet, JW; Tollner, TL; Treece, CA; Yudin, AI, 2004)	0.66
"Treatment with caffeine similarly activated CYP1A2 and related monooxygenases as well as UGT, while treatment with catechins induced UGT activity but not 7-ECOD or CN1D activity."	( Effect of components of green tea extracts, caffeine and catechins on hepatic drug metabolizing enzyme activities and mutagenic transformation of carcinogens. Fujita, S; Hara, Y; Ishizuka, M; Kazusaka, A; Maeda, Y; Nikaidou, S, 2005)	0.93
"Pretreatment with caffeine abolished the GH and GTH-II responses to PACAP."	( Intracellular calcium involvement in pituitary adenylate cyclase-activating polypeptide stimulation of growth hormone and gonadotrophin secretion in goldfish pituitary cells. Chang, JP; Sawisky, GR, 2005)	0.65
"Treatment with caffeine that abrogates the G(2) checkpoint without significantly affecting DSB rejoining increases metaphase chromosome damage of normal cells to the AT level but leaves unchanged interphase chromosome damage in G(2)."	( Checkpoint abrogation in G2 compromises repair of chromosomal breaks in ataxia telangiectasia cells. Iliakis, G; Manola, KN; Pantelias, GE; Terzoudi, GI, 2005)	0.67
"Pretreatment with caffeine (8, 15, 30 mg/kg) and theophylline (30 mg/kg) reversed the anxiolytic effect of adenosine."	( Involvement of adenosinergic receptors in anxiety related behaviours. Bishnoi, M; Kulkarni, SK; Singh, K, 2007)	0.66
"Treatment with caffeine as compared with placebo reduced the incidence of cerebral palsy (4.4% vs."	( Long-term effects of caffeine therapy for apnea of prematurity. Barrington, KJ; Davis, P; Doyle, LW; Ohlsson, A; Roberts, RS; Schmidt, B; Solimano, A; Tin, W, 2007)	1
"Rats treated with caffeine were probably more emotionally reactive than untreated controls as suggested by more immobility and defecation and urination."	( Increased emotional reactivity in rats following exposure to caffeine during adolescence. Anderson, NL; Hughes, RN, )	0.7
"Treatment with caffeine alone or ethionine alone had very little effect on reversion yield, whereas co-treatment with the two agents abolished 9AA mutagenesis."	( Mutagenesis and anti-mutagenesis in Salmonella: influence of ethionine and caffeine on yields of mutations induced by 2-aminopurine and 9-aminoacridine. MacPhee, DG; Nagel, BA; Podger, DM, 1983)	0.84
"Post-treatment with caffeine from 0 to 132 h had a dose-dependent biphasic effect on pancreatic tumorigenesis: post-treatment with the m.t.d."	( Effects of caffeine on pancreatic tumorigenesis by 4-hydroxyaminoquinoline 1-oxide in partially pancreatectomized rats. Denda, A; Emi, Y; Konishi, Y; Mikami, S; Murata, Y; Ohara, T; Sunagawa, M; Takahashi, S; Yokose, Y, 1983)	0.97
"Treatment with caffeine (75 mg/kg/day) for 12 days increases the Bmax (maximum binding capacity) for [3H]diazepam binding by 30.9% whereas the same treatment increased the Bmax for L-[3H]PIA binding by 120%."	( Up-regulation of brain [3H]diazepam binding sites in chronic caffeine-treated rats. Coffin, VL; Wu, PH, 1984)	0.85
"Pretreatment with caffeine enhanced phenytoin-induced toxicity and teratogenicity and these observations confirm that caffeine has the ability to function as a co-teratogen."	( The toxicology of chemical interactions during pregnancy in the mouse: caffeine and phenytoin. Kwasigroch, TE; Poche, PD; Skalko, RG, 1984)	0.82
"Post-treatment with caffeine alone resulted in shattered chromosomes in a high percentage of cells at the first post-irradiation mitosis as described previously."	( Induction of chromosome shattering and micronuclei by ultraviolet light and caffeine. I. Temporal relationship and antagonistic effects of the four deoxyribonucleosides. Cremer, C; Cremer, T; Simickova, M, 1980)	0.81
"Pretreatment with caffeine potentiated sodium nitroprusside-induced relaxations and cGMP increase of rings without endothelium."	( Endothelium-dependent and -independent vasodilation of isolated rat aorta induced by caffeine. Hatano, Y; Iranami, H; Mizumoto, K; Yamamoto, M; Yoshiyama, T, 1995)	0.84
"Pretreatment with caffeine (25 mg/kg, IP, -10 min) blocked the inhibition of CAR produced by the adenosine agonists, suggesting the event is mediated via purinergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)"	( Adenosine agonists reduce conditioned avoidance responding in the rat. Jarvis, MF; Martin, GE; Rossi, DJ, 1993)	0.61
"Treatment with caffeine and dbcAMP or with caffeine alone, significantly increased the number of sperm bound to each zona pellucida (96 +/- 16 and 81 +/- 17, respectively) compared to control and dbcAMP treatment (15 +/- 4 and 28 +/- 13)."	( Separate effects of caffeine and dbcAMP on macaque sperm motility and interaction with the zona pellucida. Overstreet, JW; Tollner, TL; VandeVoort, CA, 1994)	0.95
"Treatment with caffeine alone suppressed growth rate, R123 uptake, cell size, and frequency of S phase fraction in the cell cycle."	( Enhancement of CDDP cytotoxicity by caffeine is characterized by apoptotic cell death. Katsura, Y; Rokutanda, M; Shinomiya, M; Shinomiya, N; Wakiyama, H, 1994)	0.9
"Treatment with caffeine occluded phase 2 ([Ca2+]i oscillations) of the action of thyrotropin-releasing hormone (TRH) without modifying phase 1 (Ca2+ release from the intracellular stores)."	( Caffeine-induced oscillations of cytosolic Ca2+ in GH3 pituitary cells are not due to Ca2+ release from intracellular stores but to enhanced Ca2+ influx through voltage-gated Ca2+ channels. García-Sancho, J; Villalobos, C, 1996)	2.08
"Pretreatment with caffeine partially suppressed the IK(Ca) induced by either ACh or (1S,3R)-ACPD, although the inhibitory effect varied among the neurones, while pretreatment with either ACh or (1S,3R)-ACPD also partially inhibited the caffeine-induced IK(Ca)."	( Interaction between the intracellular Ca2+ stores in rat dissociated hippocampal neurones. Akaike, N; Imanishi, T; Rhee, JS; Yamanaka, H, 1996)	0.62
"TreatmenT with caFfeine to enhance calcium-induced calcium release increases the amplitude of NEB-associated calcium transients."	( Local perinuclear calcium signals associated with mitosis-entry in early sea urchin embryos. Ellis-Davies, G; Patel, R; Whitaker, M; Wilding, M; Wright, EM, 1996)	0.63
"Pretreatment with caffeine blocked the anticonvulsant effects of 2-CLA dose-dependently."	( Intra-amygdala infusion of 2-chloroadenosine suppresses amygdala-kindled seizures. Mirnajafi-Zadeh, J; Palizvan, MR; Pourgholami, MH; Rostampour, M, 1997)	0.62
"treatment with caffeine or the selective D2 (NPA) and D3 (PD 128,907) dopamine-receptor agonists in water- and caffeine-drinking rats."	( Acquisition of nicotine discrimination and discriminative stimulus effects of nicotine in rats chronically exposed to caffeine. Gasior, M; Goldberg, SR; Jaszyna, M; Shoaib, M; Yasar, S, 1999)	0.85
"Pretreatment with caffeine and ryanodine abolished STOCs and reduced NDGA-induced increase in outward current at -30 mV by approximately 60%."	( Activation of Ca(2+)-dependent K(+) current by nordihydroguaiaretic acid in porcine coronary arterial smooth muscle cells. Hirano, M; Imaizumi, Y; Muraki, K; Nagano, N; Watanabe, M; Yamamura, H, 1999)	0.63
"Treatment with caffeine in amounts equivalent to those found in the green tea extract had no effect on EE and RQ nor on urinary nitrogen or catecholamines."	( Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Chantre, P; Dulloo, AG; Duret, C; Fathi, M; Girardier, L; Mensi, N; Rohrer, D; Vandermander, J, 1999)	0.88
"Treatment with caffeine and dbcAMP was not an absolute requirement for sperm-zona pellucida binding, inasmuch as binding did occur in the absence of activators."	( Baboon spermatozoa-zona pellucida binding assay. Doncel, G; Goldberg, E; Mahony, MC; Rice, K, 2000)	0.65
"Pretreatment with caffeine ingibited all calcium respo nses to ACh."	( Calcium signalling mediated by the 9 acetylcholine receptor in a cochlear cell line from the immortomouse. Ashmore, JF; Griesinger, CB; Holley, MC; Jagger, DJ; Rivolta, MN, 2000)	0.63
"Post-treatment with caffeine greatly diminishes the yields by 4NQO of mutants in E."	( A test for mutation theory of cancer: carcinogenesis by misrepair of DNA damaged by 4-nitroquinoline 1-oxide. Kondo, S, 1977)	0.57
"Pretreatment of caffeine prior to injection by a) addition of sodium salicylate or sodium benzoate, b) increase in temperature or c) preliminary dissolution in hydrochloric acid, did not change the cardiovascular effects when injected i.v."	( The cardiovascular effects of caffeine in various forms. Atkinson, J, 1977)	0.88
"Treatment with caffeine (0-200 microgram/ml) did not result in a different response of variant cells compared with normal cells."	( Induction of sister chromatid exchanges in xeroderma pigmentosum cells after exposure to ultraviolet light. Bootsma, D; De Weerd-Kastelein, EA; Keijzer, W; Rainaldi, G, 1977)	0.6
"Treatment with caffeine after BBN had no enhancing effect and caffeine alone caused no remarkable changes."	( Effect of phenacetin and caffeine on the urinary bladder of rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine. Fukushima, S; Ito, N; Nakanishi, K; Ogiso, T; Shibata, M; Shirai, T, 1978)	0.9
"Pretreatment with caffeine enhanced the effect of MMS at high but not at low doses, suggesting an error-free repair process operating at low doses and an error-prone and caffeine-sensitive repair at higher doses."	( Factors affecting the induction of micronuclei at low doses of X-rays, MMS and dimethylnitrosamine in mouse erythroblasts. Jenssen, D; Ramel, C, 1978)	0.58
"Pretreatment with caffeine was found to shorten the hexobarbital sleeping time even though the brain concentration of the latter was actually elevated."	( The effect of caffeine on barbiturate sleeping time and brain level. Aeschbacher, HU; Atkinson, J; Domahidy, B, 1975)	0.94
"Treatment with caffeine after training has now been found to reduce greatly the amnestic effects of puromycin."	( Puromycin's suppression of memory in mice as affected by caffeine. Flexner, JB; Flexner, LB, )	0.72
"Post-treatment with caffeine greatly enhanced cell lethality and depression of cell proliferation."	( Evidence for caffeine-sensitive damage in methylazoxymethanol acetate-treated L5178Y cells. Matsudaira, H; Shinohara, K, 1976)	0.94
"Pretreatment with caffeine (10(-2) M) or ryanodine (10(-7) M) protected atria against the rise in end-diastolic [Ca]c that occurred when the tissue was exposed to conditions of simulated ischaemia."	( Effects of pretreatment with caffeine or ryanodine on the myocardial response to simulated ischaemia. Northover, BJ, 1991)	0.9
"Treatment with caffeine affected epididymal spermatozoa in a similar manner."	( Quantification of aerobic energy turnover in epididymal bull spermatozoa. Bohnensack, R; Halangk, W; Tröger, U, 1990)	0.62
"When treatment with caffeine was delayed for progressively longer times after both groups of cells received 3 Gy, the control cells achieved a higher level of survival."	( The action of caffeine on X-irradiated HeLa cells. X. Depressed recovery from potentially lethal damage in cells containing 5-bromodeoxyuridine. Beetham, KL; Labanowska, J; Tolmach, LJ, 1990)	0.95
"Treatment with caffeine (75 mg/kg/day) for 12 days increases the Bmax (maximum binding capacity) for [3H]diazepam binding by 30.9% whereas the same treatment increases the Bmax for [3H]L-PIA binding by 165%."	( Up-regulation of brain [3H]diazepam binding sites in chronic caffeine treated rats. Phillis, JW; Wu, PH, 1986)	0.85
"Pretreatment with caffeine suppressed the dark-survival curve of strain uvs-1, indicating the presence of excision enzymes involved in dark repair."	( Isolation and characterization of ultraviolet light-sensitive mutants of the blue-green alga Anacystis nidulans. Asato, Y, 1972)	0.57

Toxicity

Small studies have associated energy drinks with serious adverse health events. The aim of the present study was to further explore potential toxic consequences of chronic exposure to cocaine, caffeine and their combination on testicular physiology.

Excerpt	Reference	Relevance
" In adult rats, the LD50 of caffeine and aminophylline was the same after 24 h and after 1 week of observation: caffeine 265 mg/kg, and aminophylline 202 mg/kg (theophylline base 172 mg/kg)."	( Comparative toxicity of caffeine and aminophylline (theophylline ethylenediamine) in young and adult rats. Gorodischer, R; Kaplanski, J; Warszawski, D, 1978)	0.86
" The highest concentration of caffeine (20 mM) produced such toxic signs as reduced cell viability, increased vacuolization, and pseudopod formation."	( Cytotoxicity of caffeine in cultured heart cells. Acosta, D; Anuforo, D, )	0.77
"Twenty-two coffee drinkers (three to seven cups per day) underwent repeated double-blind trials to test for caffeine self-administration, withdrawal, and adverse effects."	( Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers. Bickel, WK; Fenwick, JW; Gulliver, SB; Higgins, ST; Hughes, JR; Hunt, WK; Mireault, GC, 1991)	1.94
" Post treatment incubation of MNU-treated HeLa cells with caffeine did not increase the toxic action of MNU."	( Properties of mer- HeLa cells sensitive or resistant to the cytotoxic effects of MNU; effects on DNA synthesis and of post treatment with caffeine. Basham, C; Roberts, JJ, )	0.58
" In six MH(-) patients with previous masseter muscle rigidity, no adverse reactions occurred in response to volatile anesthetic agents."	( Safety of general anesthesia in patients previously tested negative for malignant hyperthermia susceptibility. Allen, GC; Fletcher, JE; Rosenberg, H, 1990)	0.28
" All of the above inhibitors were also shown to potentiate the toxic effects of menadione against the Walker cell."	( Caffeine, aminoimidazolecarboxamide and dicoumarol, inhibitors of NAD(P)H dehydrogenase (quinone) (DT diaphorase), prevent both the cytotoxicity and DNA interstrand crosslinking produced by 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) in Walker cells. Boland, MP; Friedlos, F; Knox, RJ; Kotsaki-Kovatsi, VP; Marchbank, T; Roberts, JJ, 1989)	1.72
"Since it is unknown if chemicals which are generally safe in pregnancy can potentiate the embryotoxicity of cytotoxic drugs before implantation, the combined effects of cyclophosphamide (CPA) and caffeine (CF) were studied in the mouse (day 2) with CPA at 20 mg/kg, which induces a 18% resorption rate, and CF at 100 mg/kg, which does not increase embryolethality."	( Potentiating effect of caffeine on embryotoxicity of cyclophosphamide treatment in vivo during the preimplantation period. Spielmann, H; Vogel, R, 1987)	0.77
"While there are several comprehensive reviews on the toxic effects of methylxanthines in animals, data on the toxicity of these chemicals in humans has not been extensively reviewed in one document."	( Methylxanthines: toxicity to humans. 2. Caffeine. Stavric, B, 1988)	0.54
" Toxic concentrations of dT caused an increase in frequency of TGR colonies but this increase was shown to be due to effects of dT on cell growth rate, and differential sensitivity ot HGPRT- and HGPRT+ cells."	( The effects of pyrimidine nucleotides on alkylating agent induced cytotoxicity and spontaneous and induced mutation to purine analog resistance in V79 cells. Fox, M, 1985)	0.27
"" Toxic effects may result from overdose, drug interactions, or diseases that increase sensitivity to sympathomimetic agents."	( Toxicity of over-the-counter stimulants. Pentel, P, 1984)	0.27
"Nine chemicals, with a range from extremely to slightly toxic, were used to measure the oral LD50 in both fasted (24-h) and non-fasted rats."	( The effects of fasting on the acute oral toxicity of nine chemicals in the rat. Dashiell, OL; Kennedy, GL, 1984)	0.27
" Generally, toxic reactions involve excessive CNS stimulation (e."	( Managing acute toxicity from nonprescription stimulants. Conner, CS; Rumack, BH; Sawyer, DR, )	0.13
"The desirable effects of methylxanthine use in the neonate, appropriately prescribed and monitored, outweigh the importance of adverse effects."	( Adverse effects of caffeine and theophylline in the newborn infant. Aranda, JV; Clozel, M; Howell, J, 1981)	0.59
" We conclude from this study that caffeine-augmented ECT is safe and effective in increasing seizure duration in the elderly."	( Safety and efficacy of caffeine-augmented ECT in elderly depressives: a retrospective study. Grossberg, GT; Kelsey, MC, 1995)	0.88
"The aim of this study was an experimental assessment of the influence of caffeine on the symptoms of the toxic action of paracentamol in mice as well as a detailed analysis if paracetamol pharmacokinetics in men receiving caffeine at the same time."	( [Influence of caffeine on toxicity and pharmacokinetics of paracetamol]. Raińska-Giezek, T, 1995)	0.88
" To investigate toxic interactions between PB and other drugs, male ICR mice received contralateral ip injections of either a selected adrenergic drug or caffeine, followed 15 min later by PB."	( Potentiation of pyridostigmine bromide toxicity in mice by selected adrenergic agents and caffeine. Chaney, LA; Hume, AS; Moss, JI; Mozingo, JR; Rockhold, RW, 1997)	0.72
" Results indicated that the lowest concentration of guarana tested was not toxic and that the IC50 values calculated with the NR, KB, and MTT assays were lower than the highest concentration tested (40 mg/ml)."	( Evaluation of the toxicity of guarana with in vitro bioassays. Diaz, MM; Lopez, A; Muñoz-Mingarro, D; Pozuelo, JM; Santa Maria, A, 1998)	0.3
" Caffeine was used 50, 150, 250 and 350 microM concentrations and the most toxic dose for it was found to be 350 microM."	( Response to nimodipine in caffeine-induced neurotoxicity in cerebellar granular cell culture of rat pups. Düzenli, S; Gepdiremen, A; Ikbal, M; Sönmez, S; Tuna, S, 1998)	1.51
" The global incidence of adverse events was 45% higher with EC, though not significant (32 vs."	( Comparative efficacy and safety of calcium carbasalate plus metoclopramide versus ergotamine tartrate plus caffeine in the treatment of acute migraine attacks. Geraud, G; Gómez, JP; Henry, P; Joffroy, A; Lainez, JM; Le Jeunne, C; Liaño, H; Pradalier, A; Titus i Albareda, F, 1999)	0.52
"The results presented in this study indicate that the toxic response brought about by increasing concentrations of tert-butylhydroperoxide in CHP100 cells was mitigated significantly by exogenously added nitric oxide donors via a cyclic GMP-independent mechanism."	( Different signalling pathways mediate the opposite effects of endogenous versus exogenous nitric oxide on hydroperoxide toxicity in CHP100 neuroblastoma cells. Cantoni, O; Clementi, E; Guidarelli, A; Sciorati, C, 1999)	0.3
" Adverse events were negligible and did not differ between the CE and PL groups."	( Safety and efficacy of treatment with an ephedrine/caffeine mixture. The first double-blind placebo-controlled pilot study in adolescents. Erhardt, E; Jeges, S; Molnár, D; Török, K, 2000)	0.56
"According to the present pilot study, CE can be a safe and effective compound for the treatment of obesity in adolescents."	( Safety and efficacy of treatment with an ephedrine/caffeine mixture. The first double-blind placebo-controlled pilot study in adolescents. Erhardt, E; Jeges, S; Molnár, D; Török, K, 2000)	0.56
"In order to investigate gene expression changes associated with cytotoxicity, we used cDNA arrays to monitor the expression of over 5,000 genes in response to toxic stress in the HepG2 liver cell line."	( Gene expression changes associated with cytotoxicity identified using cDNA arrays. Gore, MA; Morshedi, MM; Reidhaar-Olson, JF, 2000)	0.31
" Adverse events were generally mild or moderate and transient."	( Efficacy, tolerability and safety of oral eletriptan and ergotamine plus caffeine (Cafergot) in the acute treatment of migraine: a multicentre, randomised, double-blind, placebo-controlled comparison. Diener, HC; Jansen, JP; Pascual, J; Pitei, D; Reches, A; Steiner, TJ, 2002)	0.55
"Caffeine (1,3,7-trimethylxanthine), a compound present in beverages such as tea and coffee, is known to be toxic at high concentrations."	( Caffeine enhances the calcium-dependent cardiac mitochondrial permeability transition: relevance for caffeine toxicity. Moreno, AJ; Oliveira, PJ; Sardão, VA, 2002)	3.2
"In this 6-month placebo-controlled trial, herbal ephedra/caffeine (90/192 mg/day) promoted body weight and body fat reduction and improved blood lipids without significant adverse events."	( Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Blanchard, D; Boozer, CN; Daly, PA; Homel, P; Meredith, T; Nasser, JA; Solomon, JL; Strauss, R, 2002)	0.91
" Reports of adverse events associated with the use of these non-prescription supplements have raised concerns in the United States regulatory community."	( The safety and efficacy of pharmaceutical and herbal caffeine and ephedrine use as a weight loss agent. Greenway, FL, 2001)	0.56
" This protection was associated with decreased formation of the toxic metabolite of APAP."	( Effect of caffeine on acetaminophen hepatotoxicity in cultured hepatocytes treated with ethanol and isopentanol. Bement, J; Chatfield, K; DiPetrillo, K; Jeffery, E; Kostrubsky, V; Sinclair, J; Sinclair, P; Wood, S; Wrighton, S, 2002)	0.72
" We conclude that these drugs are toxic to renal inner medullary collecting duct cells under the conditions of high osmolality normally present in the inner medulla, that combinations of the drugs are more toxic than are the drugs individually, and that the toxicity includes induction of proliferation of these cells that are otherwise quiescent in the presence of high osmolality."	( Toxicity of acetaminophen, salicylic acid, and caffeine for first-passage rat renal inner medullary collecting duct cells. Burg, MB; Cai, Q; Dmitrieva, NI; Ferguson, D; Michea, LF; Rocha, G, 2003)	0.58
"We searched 9 databases using the terms ephedra, ephedrine, adverse effect, side effect, efficacy, effective, and toxic."	( Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. Gagné, J; Hardy, ML; Jungvig, L; Maglione, M; Mojica, WA; Morton, SC; Rhodes, SL; Shekelle, PG; Suttorp, MJ, 2003)	0.32
"Eligible studies were controlled trials of ephedra or ephedrine used for weight loss or athletic performance and case reports of adverse events associated with such use."	( Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. Gagné, J; Hardy, ML; Jungvig, L; Maglione, M; Mojica, WA; Morton, SC; Rhodes, SL; Shekelle, PG; Suttorp, MJ, 2003)	0.32
" It was found that both Caco-2 and Hep G2 cells can metabolize B[a]P to toxic metabolites including B[a]P-7,8-hydrodiol (7,8-diol), an immediate precursor to the highly-reactive ultimate toxicant of B[a]P, B[a]P-7,8-hydrodiol-9,10-epoxide (BPDE), possibly mediated by cytochrome P450 1A1/2 activity."	( Feasibility of a simple double-layered coculture system incorporating metabolic processes of the intestine and liver tissue: application to the analysis of benzo[a]pyrene toxicity. Choi, S; Nishikawa, M; Sakai, Y; Sakoda, A, 2004)	0.32
" High ATP levels may postpone the toxic cascade."	( Reactive blue prevented caffeine-induced neurotoxicity by an independent mechanism from intracellular calcium currents in cell culture from auditory cortex of rats. Bakuridze, K; Büyükokuroglu, ME; Düzenli, S; Gepdiremen, A; Halici, Z; Uçüncü, H, 2005)	0.64
"Fatty acid ethyl esters are ethanol metabolites inducing sustained, toxic elevations of the acinar cytosolic free calcium ion concentration ([Ca(2+)](C)) implicated in pancreatitis."	( Fatty acid ethyl esters cause pancreatic calcium toxicity via inositol trisphosphate receptors and loss of ATP synthesis. Barrow, S; Criddle, DN; Fistetto, G; Murphy, J; Neoptolemos, JP; Petersen, OH; Sutton, R; Tepikin, AV, 2006)	0.33
" The acute effects stemming from this association, in tandem with the final potentiation of serotonergic terminals injury, provide evidence of the potentially greater long-term adverse effects of this particular recreational drug combination."	( Association of caffeine to MDMA does not increase antinociception but potentiates adverse effects of this recreational drug. Camarasa, J; Escubedo, E; Pubill, D, 2006)	0.69
" Extracts of Athrixia phylicoides and Athrixia elata were tested for toxic effects to brine shrimp larvae and the Vero kidney cell line."	( Evaluation of Athrixia bush tea for cytotoxicity, antioxidant activity, caffeine content and presence of pyrrolizidine alkaloids. Eloff, JN; McGaw, LJ; Steenkamp, V, 2007)	0.57
" Was shown relationship between concentration and toxic effect that is nonlinear and characterized with three parts different in induced damages level."	( [Mechanisms of 232Th effects on Chlorella vulgaris Beljer and modifications of it's toxic effect with caffeine and buthionine sulfoximine]. Belykh, ES; Evseeva, TI; Geras'kin, SA; Maĭstrenko, TA, )	0.35
" Our results indicate that it is possible to estimate LOEDs by integrating in vitro toxicity data as surrogates for lowest observed target tissue levels with PBBK models, provided that some knowledge about toxic mechanisms is known."	( Integration of in vitro neurotoxicity data with biokinetic modelling for the estimation of in vivo neurotoxicity. Blaauboer, B; Forsby, A, 2007)	0.34
"To describe benefits and adverse effects associated with the consumption of energy drinks."	( Safety issues associated with commercially available energy drinks. Clauson, KA; McQueen, CE; Persad, N; Shields, KM, )	0.13
" Commonly reported adverse effects seen with caffeine in the quantities present in most energy drinks are insomnia, nervousness, headache, and tachycardia."	( Safety issues associated with commercially available energy drinks. Clauson, KA; McQueen, CE; Persad, N; Shields, KM, )	0.39
"The amounts of guarana, taurine, and ginseng found in popular energy drinks are far below the amounts expected to deliver either therapeutic benefits or adverse events."	( Safety issues associated with commercially available energy drinks. Clauson, KA; McQueen, CE; Persad, N; Shields, KM, )	0.13
" In the present study, potential adverse effects of a standardized heat-sterilized green tea catechin (GTC-H) preparation was investigated following gavage administration to rats at doses of 0, 120, 400, 1200 mg/kg/day for 6 months."	( Safety assessment of heat-sterilized green tea catechin preparation: a 6-month repeat-dose study in rats. Beck, MJ; Bruner, RH; Chengelis, CP; Kirkpatrick, JB; Morita, O; Tamaki, Y, 2009)	0.35
" The findings of current in vitro studies now suggest that bactericidal concentrations of SCC1 are not toxic to airway epithelial cells in primary culture."	( In vitro and murine efficacy and toxicity studies of nebulized SCC1, a methylated caffeine-silver(I) complex, for treatment of pulmonary infections. Brody, SL; Cannon, CL; Capps, GH; Hindi, KM; Hogue, LA; Ibricevic, A; Kascatan-Nebioglu, A; Vajravelu, RK; Walter, MJ; Youngs, WJ, 2009)	0.58
" The present study focused on monitoring and adjusting serum caffeine levels during caffeine-potentiated chemotherapy to reduce adverse effects."	( Impact of serum caffeine monitoring on adverse effects and chemotherapeutic responses to caffeine-potentiated chemotherapy for osteosarcoma. Hayashi, K; Kawahara, M; Miyamoto, K; Shirai, T; Takeuchi, A; Tomita, K; Tsuchiya, H; Yamamoto, N; Yamauchi, K, 2009)	0.94
"Hematological toxic events were well tolerated in both groups."	( Impact of serum caffeine monitoring on adverse effects and chemotherapeutic responses to caffeine-potentiated chemotherapy for osteosarcoma. Hayashi, K; Kawahara, M; Miyamoto, K; Shirai, T; Takeuchi, A; Tomita, K; Tsuchiya, H; Yamamoto, N; Yamauchi, K, 2009)	0.7
" Moderate caffeine consumption is considered safe and its use as a food ingredient has been approved, within certain limits, by numerous regulatory agencies around the world."	( Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. Gonzalez de Mejia, E; Heckman, MA; Weil, J, 2010)	2.21
" An understanding of structure-activity relationships (SARs) of chemicals can make a significant contribution to the identification of potential toxic effects early in the drug development process and aid in avoiding such problems."	( Developing structure-activity relationships for the prediction of hepatotoxicity. Fisk, L; Greene, N; Naven, RT; Note, RR; Patel, ML; Pelletier, DJ, 2010)	0.36
" Caffeine, the most physiologically active ingredient in energy drinks, is generally considered safe by the US Food and Drug Administration (FDA), although adverse effects can occur at varying amounts."	( Energy drinks: a review of use and safety for athletes. Duchan, E; Feucht, C; Patel, ND, 2010)	1.27
" The results indicate that caffeine potentiates the toxic effects of methamphetamine, possibly via a mechanism involving an increase in dopamine release and excess ROS generation."	( Caffeine potentiates methamphetamine-induced toxicity both in vitro and in vivo. Govitrapong, P; Jaisin, Y; Morales, NP; Plasen, D; Plasen, S; Ratanachamnong, P; Sanvarinda, Y; Sinchai, T, 2011)	2.11
" In this work, the antinociceptive and toxic effects of two new coordination complexes: Cu₂(fen)₄(caf)₂ [fen: fenoprofenate anion; caf: caffeine] and Cu₂(fen)₄(dmf)₂ [dmf: N-N'-dimethylformamide] were evaluated in mice."	( Anti-nociceptive activity and toxicity evaluation of Cu(II)-fenoprofenate complexes in mice. Agotegaray, M; Bras, C; Gandini, NA; Gumilar, F; Minetti, A; Quinzani, O, 2012)	0.58
" We analyzed toxic and trace element levels of nine herbal products and found that these herbal products, even in low amounts, contain Pb, Al, Ni, and Ba."	( How safe is the use of herbal weight-loss products sold over the internet? Celbis, O; Erdogan, S; Kapucu, H; Karakoc, Y; Onal, Y; Ozdemir, B; Sahin, I, 2013)	0.39
" Moreover, they also may become contaminated with toxic metals."	( How safe is the use of herbal weight-loss products sold over the internet? Celbis, O; Erdogan, S; Kapucu, H; Karakoc, Y; Onal, Y; Ozdemir, B; Sahin, I, 2013)	0.39
" Recent and significant literature describing adverse events associated with energy drink use are reviewed."	( Toxicity of energy drinks. Babu, KM; Ganetsky, M; Wolk, BJ, 2012)	0.38
" The most frequent adverse events (AEs) were headache (60 %) and palpitations (40 %)."	( Cardiovascular safety of anagrelide in healthy subjects: effects of caffeine and food intake on pharmacokinetics and adverse reactions. Datino, T; Fernández-Avilés, F; Figueiras-Graillet, L; Franklin, R; Gama, JG; Jones, C; Martínez-Sellés, M, 2013)	0.63
" Because ephedrine has cardiovascular effects that may be exacerbated during physical exercise, the purpose of this study was to determine whether extracts containing synephrine produced adverse effects on the cardiovascular system in exercising rats."	( Cardiovascular toxicity of Citrus aurantium in exercised rats. Abdel-Rahman, A; Fabricant, D; George, NI; Hansen, DK; Pellicore, LS; White, GE, 2013)	0.39
" Adverse effects reported in association with preworkout supplements include gastrointestinal symptoms, cardiac arrhythmia, blood pressure increases, and potential effects on lipids and blood glucose."	( Efficacy and safety of ingredients found in preworkout supplements. Ambrose, PJ; Eudy, AE; Gordon, LL; Hockaday, BC; Lee, DA; Lee, V; Luu, D; Martinez, CA, 2013)	0.39
" Although it is difficult to assess the risk of spontaneous abortion with caffeine consumption, most of the data do not suggest an increased risk of adverse pregnancy, fertility, or neurodevelopmental outcomes with caffeine consumption of 300 mg/d or less from all sources."	( Is caffeine consumption safe during pregnancy? Bozzo, P; Koren, G; Morgan, S, 2013)	1.24
" The CAFF 9mg trial drastically increased the frequency of the adverse side effects (15%-62%)."	( Neuromuscular responses to incremental caffeine doses: performance and side effects. Fernández-Elías, VE; Mora-Rodríguez, R; Muñoz, G; Muñoz-Guerra, J; Ortega, JF; Pallarés, JG, 2013)	0.66
" A dose of 3 mg · kg(-1) is enough to improve high-velocity muscle actions against low loads, whereas a higher caffeine dose (9 mg · kg(-1)) is necessary against high loads, despite the appearance of adverse side effects."	( Neuromuscular responses to incremental caffeine doses: performance and side effects. Fernández-Elías, VE; Mora-Rodríguez, R; Muñoz, G; Muñoz-Guerra, J; Ortega, JF; Pallarés, JG, 2013)	0.87
"This pilot study assessed the prevalence of physiologic and behavioral adverse effects among adolescent (13-17 years) and adult (18-25 years) emergency department patients who reported energy drink and/or caffeinated-only beverage use within the 30 days prior to emergency department presentation."	( Behavioral and physiologic adverse effects in adolescent and young adult emergency department patients reporting use of energy drinks and caffeine. Babu, KM; Baird, JR; Cotter, BV; Jackson, DA; Linakis, JG; Merchant, RC; Nirenberg, T, 2013)	0.59
" Multivariable logistic regression and negative binomial regression models, adjusted for age, gender, and substance use, were created to compare the occurrence of each adverse effect between energy drink and caffeinated-only beverage users."	( Behavioral and physiologic adverse effects in adolescent and young adult emergency department patients reporting use of energy drinks and caffeine. Babu, KM; Baird, JR; Cotter, BV; Jackson, DA; Linakis, JG; Merchant, RC; Nirenberg, T, 2013)	0.59
"Energy drink users and substance users are more likely to report specific physiologic and behavioral adverse effects."	( Behavioral and physiologic adverse effects in adolescent and young adult emergency department patients reporting use of energy drinks and caffeine. Babu, KM; Baird, JR; Cotter, BV; Jackson, DA; Linakis, JG; Merchant, RC; Nirenberg, T, 2013)	0.59
"Small studies have associated energy drinks-beverages that typically contain high concentrations of caffeine and other stimulants-with serious adverse health events."	( An analysis of energy-drink toxicity in the National Poison Data System. Arheart, KL; Benson, BE; Bronstein, AC; Franco, VI; Hershorin, ER; Lipshultz, SE; Schaechter, JL; Seifert, SA; Seifert, SM, 2013)	0.61
"To assess the incidence and outcomes of toxic exposures to caffeine-containing energy drinks, including caffeinated alcoholic energy drinks, and to evaluate the effect of regulatory actions and educational initiatives on the rates of energy drink exposures."	( An analysis of energy-drink toxicity in the National Poison Data System. Arheart, KL; Benson, BE; Bronstein, AC; Franco, VI; Hershorin, ER; Lipshultz, SE; Schaechter, JL; Seifert, SA; Seifert, SM, 2013)	0.63
" The incidence of moderate to major adverse effects of energy drink-related toxicity was 15."	( An analysis of energy-drink toxicity in the National Poison Data System. Arheart, KL; Benson, BE; Bronstein, AC; Franco, VI; Hershorin, ER; Lipshultz, SE; Schaechter, JL; Seifert, SA; Seifert, SM, 2013)	0.39
" No changes in EKG-corrected QT interval were observed, and no serious adverse events were reported."	( Effects of a pre-workout supplement on lean mass, muscular performance, subjective workout experience and biomarkers of safety. Ferrando, AA; Gothard, MD; Habowski, SM; Hofheins, JE; Kedia, AW; Lopez, HL, 2014)	0.4
" Nearly half of these visits involved adverse effects occurring from product misuse."	( Proposed actions for the US Food and Drug Administration to implement to minimize adverse effects associated with energy drink consumption. Colby, DA; Devine, P; Thorlton, J, 2014)	0.4
" No adverse effects were noted for renal and hepatic clinical blood markers, resting heart rate, or BP."	( Ingesting a preworkout supplement containing caffeine, creatine, β-alanine, amino acids, and B vitamins for 28 days is both safe and efficacious in recreationally active men. Carson, LR; Esposito, EN; Fairman, CM; Falcone, PH; Joy, JM; Kendall, KL; Kim, MP; Moon, JR; Mosman, MM; Serrano, ER; Spradley, BD; Tai, CY, 2014)	0.66
" The ingestion of low to moderate doses of caffeinated energy drinks has been associated with adverse side effects such as insomnia or increased nervousness."	( The use of energy drinks in sport: perceived ergogenicity and side effects in male and female athletes. Abian-Vicen, J; Areces, F; Del Coso, J; Gallo-Salazar, C; Gonzalez-Millán, C; Lara, B; Ruiz-Vicente, D; Salinero, JJ, 2014)	0.4
" A tandem extraction protocol has been devised by exploiting the quick easy cheap effective rugged and safe (QuEChERS) scheme for extraction, coupled to a dispersive liquid-liquid micro-extraction (DLLME) in order to drastically reduce caffeine content in the final extract."	( Analysis of organo-chlorine pesticides residue in raw coffee with a modified "quick easy cheap effective rugged and safe" extraction/clean up procedure for reducing the impact of caffeine on the gas chromatography-mass spectrometry measurement. Bresin, B; Casetta, B; Del Bianco, C; Fabbro, D; Mancini, MA; Piol, M, 2015)	0.79
" Previous study demonstrated that caffeine potentiates the toxic effect of METH in association with the production of reactive oxygen species and the induction of apoptosis."	( Autophagy inhibition by caffeine increases toxicity of methamphetamine in SH-SY5Y neuroblastoma cell line. Govitrapong, P; Jantaratnotai, N; Jariyawat, S; Pitaksalee, R; Sanvarinda, P; Sanvarinda, Y; Sinchai, T; Thampithak, A; Tuchinda, P, 2015)	1
" The present study was undertaken to evaluate the reproductive toxic effect of meclizine and caffeine combination."	( Prenatal and developmental toxicity study of meclizine and caffeine combination in female albino Wistar rats. Alvin, JM; Sandeep, M, 2014)	0.87
" However, the existing protocols for predictive transcriptional signatures do not establish appropriate guidelines for dose selection or account for the fact that toxic agents may have pleiotropic effects."	( Development of a toxicogenomics signature for genotoxicity using a dose-optimization and informatics strategy in human cells. Aubrecht, J; Chen, R; Fornace, AJ; Heard, P; Hyduke, DR; Li, HH; Yauk, CL, 2015)	0.42
" Far-UV CD spectroscopy and fluorescence quenching analysis revealed that caffeine induced transient changes in this intrinsically disordered protein, forming a non-native species that enhanced the rate of aggregation of α-synuclein and modified the population of mature aggregates, introducing a higher fraction of amorphous, less toxic species."	( Understanding Caffeine's Role in Attenuating the Toxicity of α-Synuclein Aggregates: Implications for Risk of Parkinson's Disease. Kardani, J; Roy, I, 2015)	1.01
" One such case describes a caffeine-naïve service member who suffered an adverse reaction after taking an allegedly moderate dose of caffeine from a pill he obtained from a teammate."	( Caffeine Toxicity Due to Supplement Use in Caffeine--Naïve Individual: A Cautionary Tale. Leggit, JC; Lystrup, RM, 2015)	2.16
" The aim of the present study was to further explore potential toxic consequences of chronic exposure to cocaine, caffeine, and their combination on testicular physiology."	( Psychostimulant-Induced Testicular Toxicity in Mice: Evidence of Cocaine and Caffeine Effects on the Local Dopaminergic System. Bisagno, V; Cadet, JL; Garcia-Rill, E; González, B; González, CR; Matzkin, ME; Muñiz, JA; Urbano, FJ; Vitullo, AD, 2015)	0.86
" Twenty-three adverse drug reactions were observed in 21 neonates (4."	( The Real-World Routine Use of Caffeine Citrate in Preterm Infants: A European Postauthorization Safety Study. Carnielli, VP; Fabbri, L; Ferrari, F; Kiechl-Kohlendorfer, U; Lasagna, G; Lista, G; Papagaroufalis, K; Polackova, R; Saenz, P, 2016)	0.72
"The use of this caffeine citrate is safe for the management of AOP in a real-world setting."	( The Real-World Routine Use of Caffeine Citrate in Preterm Infants: A European Postauthorization Safety Study. Carnielli, VP; Fabbri, L; Ferrari, F; Kiechl-Kohlendorfer, U; Lasagna, G; Lista, G; Papagaroufalis, K; Polackova, R; Saenz, P, 2016)	1.07
" In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs."	( Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats. Fone, KC; Green, AR; King, MV; Shortall, SE, 2016)	2.1
"Caffeine is considered a very safe stimulant and is widely consumed in a variety of forms, from pure caffeine to beverages and foods."	( Caffeine toxicity in forensic practice: possible effects and under-appreciated sources. Byard, RW; Farrington, RL; Hoban, C; Musgrave, IF, 2016)	3.32
"An acute LD50 is a statistically derived amount of a substance that can be expected to cause death in 50% of the animals when given by a specified route as a single dose and the animals observed for a specified time period."	( The acute lethal dose 50 (LD50) of caffeine in albino rats. Adamson, RH, 2016)	0.71
"Obesity is a major global health problem associated with various adverse effects."	( Genotoxicity of antiobesity drug orlistat and effect of caffeine intervention: an in vitro study. Chakrabarti, M; Ghosh, I; Ghosh, M; Jana, A; Mukherjee, A, 2017)	0.7
"The objective of this evidence-based review was to examine whether supplementation with l-arginine, in combination with caffeine and/or creatine, is safe and whether it enhances athletic performance or improves recovery from exhaustion for military personnel."	( Safety and performance benefits of arginine supplements for military personnel: a systematic review. Barrett, ML; Brooks, JR; Cantilena, L; Chung, M; Costello, RB; Deuster, P; Dwyer, J; Giancaspro, GI; Gorecki, DK; Hardy, ML; Jones, D; Jordan, SA; Low Dog, T; Marles, RJ; Maughan, RJ; Oketch-Rabah, H; Osterberg, RE; Rodda, BE; Sarma, ND; Valerio, LG; Wolfe, RR; Zuniga, JM, 2016)	0.64
"Information from clinical trials and adverse event reports were collected from 17 databases and 5 adverse event report portals."	( Safety and performance benefits of arginine supplements for military personnel: a systematic review. Barrett, ML; Brooks, JR; Cantilena, L; Chung, M; Costello, RB; Deuster, P; Dwyer, J; Giancaspro, GI; Gorecki, DK; Hardy, ML; Jones, D; Jordan, SA; Low Dog, T; Marles, RJ; Maughan, RJ; Oketch-Rabah, H; Osterberg, RE; Rodda, BE; Sarma, ND; Valerio, LG; Wolfe, RR; Zuniga, JM, 2016)	0.43
" Short-term supplementation with arginine may result in adverse gastrointestinal and cardiovascular effects."	( Safety and performance benefits of arginine supplements for military personnel: a systematic review. Barrett, ML; Brooks, JR; Cantilena, L; Chung, M; Costello, RB; Deuster, P; Dwyer, J; Giancaspro, GI; Gorecki, DK; Hardy, ML; Jones, D; Jordan, SA; Low Dog, T; Marles, RJ; Maughan, RJ; Oketch-Rabah, H; Osterberg, RE; Rodda, BE; Sarma, ND; Valerio, LG; Wolfe, RR; Zuniga, JM, 2016)	0.43
" MeHg was more toxic than HgCl2."	( Glutamate‑mediated effects of caffeine and interferon‑γ on mercury-induced toxicity. Engin, AB; Engin, ED; Golokhvast, K; Spandidos, DA; Tsatsakis, AM, 2017)	0.74
" Thus, as an update to this foundational publication, we conducted a systematic review of data on potential adverse effects of caffeine published from 2001 to June 2015."	( Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Britt, J; Brorby, GP; Doepker, C; Goldberger, J; Harvey, S; Henderson, R; Lieberman, HR; Myers, E; O'Brien, C; Peck, J; Tenenbein, M; Urban, J; Weaver, C; Welsh, BT; Wikoff, D, 2017)	0.91
"Difference in apneic spells, associated respiratory morbidity, and acute adverse events were assessed."	( Comparative Efficacy and Safety of Caffeine and Aminophylline for Apnea of Prematurity in Preterm (≤34 weeks) Neonates: A Randomized Controlled Trial. Bhat Y, R; Jayashree, P; Kamath, A; Lewis, LES; Najih, M; Shashikala, -; Shivakumar, M, 2017)	0.73
" These results raise the possibility that the phenobarbital-induced adverse effects could be reduced by a co-treatment with caffeine."	( Caffeine Protects Against Anticonvulsant-Induced Neurotoxicity in the Developing Rat Brain. Bendix, I; Bührer, C; Endesfelder, S; Schiller, C; Sifringer, M; Weichelt, U, 2017)	2.1
" Stable O/W emulsions and gels were prepared containing the less toxic choline-based ILs and caffeine."	( Choline- versus imidazole-based ionic liquids as functional ingredients in topical delivery systems: cytotoxicity, solubility, and skin permeation studies. Araújo, MEM; Baby, AR; Fernandes, AS; Júlio, A; Mota, JP; Rosado, C; Santos de Almeida, T; Saraiva, N, 2017)	0.67
" Adverse events were infrequent and mostly mild or moderate across treatment groups."	( Efficacy and safety of a fixed-dose combination of ibuprofen and caffeine in the management of moderate to severe dental pain after third molar extraction. Hegewisch, A; Lange, R; Muse, DD; Richter, E; Weiser, T, 2018)	0.72
" No adverse effects were reported in response to the bitter orange (p-synephrine)."	( Safety evaluation of p-synephrine following 15 days of oral administration to healthy subjects: A clinical study. Shara, M; Smadi, MM; Stohs, SJ, 2018)	0.48
" UCB concentration toxic to 50% of astrocytes, and caffeine concentration increasing cell viability 100% were used in experiments."	( Caffeine prevents bilirubin-induced cytotoxicity in cultured newborn rat astrocytes. Akça, H; Deliktaş, M; Demiray, A; Ergin, H; Özdemir, MB; Özdemir, ÖMA, 2019)	2.21
" On the other hand, the adverse event rates in the caffeine group and the aminophylline group were 70."	( [Comparative Study of the Efficacy and Safety of Caffeine and Aminophylline for the Treatment of Apnea in Preterm Infants]. Kamimura, H; Nagasato, A; Nakamura, M, 2018)	0.99
"Ephedrine alkaloids-free Ephedra Herb extract (EFE) has been developed to eliminate the adverse effects caused by ephedrine alkaloid-induced sympathetic hyperactivation."	( Ephedrine Alkaloids-Free Ephedra Herb Extract, EFE, Has No Adverse Effects Such as Excitation, Insomnia, and Arrhythmias. Amakura, Y; Goda, Y; Hakamatsuka, T; Hanawa, T; Hyuga, M; Hyuga, S; Kobayashi, Y; Maruyama, T; Odaguchi, H; Oshima, N; Takahashi, J; Takemoto, H; Uchiyama, N; Yamashita, T, 2018)	0.48
" Higher blood levels of caffeine within the range considered therapeutic and safe for human infants correlated with increased neuroapoptosis."	( Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain. Brambrink, AM; Dissen, GA; Ikonomidou, C; Johnson, SA; Manzella, FM; Martin, LD; Masuoka, KL; Noguchi, KK; Olney, JW; Schenning, KJ; Williams, SL, 2018)	2.23
"Caffeine use is common in children and adolescents, but the recommendations for safe consumption are based on decades-old data collected exclusively in adults."	( Review: Trends, Safety, and Recommendations for Caffeine Use in Children and Adolescents. Temple, JL, 2019)	2.21
" More attention is being paid to the potential adverse effects of both acute and chronic caffeine use, and additional regulations surrounding the sale and marketing of highly caffeinated beverages are now being considered."	( Review: Trends, Safety, and Recommendations for Caffeine Use in Children and Adolescents. Temple, JL, 2019)	0.99
" There were no significant group differences in other adverse events including in-hospital death (P>0."	( Efficacy and Safety of Different Maintenance Doses of Caffeine Citrate for Treatment of Apnea in Premature Infants: A Systematic Review and Meta-Analysis. Chen, J; Chen, X; Jin, L, 2018)	0.73
"Amyloid-β, one of the hallmarks of Alzheimer's disease (AD), is toxic to neurons and can also cause brain cell death."	( Ingredients in Zijuan Pu'er Tea Extract Alleviate β-Amyloid Peptide Toxicity in a Bai, S; Du, F; Fu, X; Jiao, Y; Ma, J; Wang, L; Zhou, L, 2019)	0.51
" The two groups were compared in terms of response rate and incidence rate of adverse events."	( [Clinical effect and safety of different maintenance doses of caffeine citrate in treatment of apnea in very low birth weight preterm infants: a prospective randomized controlled trial]. Lyu, Y; Wang, LF; Yang, ZY; Zhang, HT; Zhang, X, 2019)	0.75
"Higher maintenance dose of caffeine citrate has a better clinical effect than lower maintenance dose of caffeine citrate in the treatment of apnea in very low birth weight preterm infants, without increasing the incidence rates of adverse drug reactions and serious complications in preterm infants."	( [Clinical effect and safety of different maintenance doses of caffeine citrate in treatment of apnea in very low birth weight preterm infants: a prospective randomized controlled trial]. Lyu, Y; Wang, LF; Yang, ZY; Zhang, HT; Zhang, X, 2019)	1.05
"This study aimed to verify the toxic effects of prenatal caffeine exposure (PCE) on the podocyte development in male offspring, and to explore the underlying intrauterine programming mechanisms."	( Decreased H3K9ac level of KLF4 mediates podocyte developmental toxicity induced by prenatal caffeine exposure in male offspring rats. Ao, Y; Chen, H; Cheng, H; He, H; Li, B; Wang, H; Zhao, X; Zhu, Y, 2019)	0.98
"To describe and compare caffeinated energy drink adverse event (AE) report/exposure call data from the US Food and Drug Administration Center for Food Safety and Applied Nutrition's Adverse Event Reporting System (CAERS) and the American Association of Poison Control Centers' National Poison Data System (NPDS)."	( Caffeinated energy drinks: adverse event reports to the US Food and Drug Administration and the National Poison Data System, 2008 to 2015. Jones, OE; Lurie, P; Markon, AO; Punzalan, CM; Wolpert, B, 2019)	0.51
" The final result is a ready-to-use compounding vehicle, containing minimal excipients, safe for children's use and stable for 6 months."	( Development of a safe and versatile suspension vehicle for pediatric use: Formulation development. Alarie, H; Leclair, G; Roullin, VG, 2019)	0.51
" In this work, we reported a novel kind of BiOI@CuS nanoparticle to achieve safe and effective therapy of lung cancer by co-loading hydrochloric acid doxorubicin (DOX) and aspirin phenacetin and caffeine (APC)."	( Construction of DOX/APC co-loaded BiOI@CuS NPs for safe and highly effective CT imaging and chemo-photothermal therapy of lung cancer. Cheng, J; He, D; Huang, G; Li, W; Wang, R; Zhang, Y; Zhu, J, 2019)	0.7
"Early use of caffeine can shorten the duration of caffeine treatment, oxygen supply time, and length of hospital stay, with little adverse effect, in preterm infants with a gestational age of ≤31 weeks."	( [Safety and efficacy of caffeine use started at different time in preterm infants: a multicenter study in Jiangsu Province, China]. Cheng, R; Gu, HB; Jiang, SH; Jiang, SY; Liu, SL; Qiao, LX; Wu, Q; Yang, Y; Yang, ZM, 2020)	1.23
" Inhibiting SSAO activity by natural agents might reduce the potential adverse effects of creatine metabolism in population of T2DM."	( Beneficial Impact of Semicarbazide-Sensitive Amine Oxidase Inhibition on the Potential Cytotoxicity of Creatine Supplementation in Type 2 Diabetes Mellitus. Deng, Y; Papukashvili, D; Rcheulishvili, N, 2020)	0.56
"To examine differences in the frequency and severity of federally reported adverse events between caffeine-containing and non-caffeine-containing products while also identifying the category of caffeine-containing products associated with the highest frequency and severity of adverse events."	( Adverse Events Reported to the United States Food and Drug Administration Related to Caffeine-Containing Products. Erickson, JL; Fischer, KM; Harty, PS; Jagim, AR; Kerksick, CM, 2020)	1
"All adverse event reports that met specified eligibility criteria and were submitted to the Center for Food Safety and Applied Nutrition Adverse Event Reporting System between January 1, 2014, and June 29, 2018, were extracted."	( Adverse Events Reported to the United States Food and Drug Administration Related to Caffeine-Containing Products. Erickson, JL; Fischer, KM; Harty, PS; Jagim, AR; Kerksick, CM, 2020)	0.78
"Energy and preworkout products saw a significant increase in the odds of the adverse event experienced being death rather than the other less severe outcomes relative to the noncaffeinated group."	( Adverse Events Reported to the United States Food and Drug Administration Related to Caffeine-Containing Products. Erickson, JL; Fischer, KM; Harty, PS; Jagim, AR; Kerksick, CM, 2020)	0.78
"Caffeine-containing products have a greater association with severe adverse events compared with non-caffeine-containing products."	( Adverse Events Reported to the United States Food and Drug Administration Related to Caffeine-Containing Products. Erickson, JL; Fischer, KM; Harty, PS; Jagim, AR; Kerksick, CM, 2020)	2.22
" Thus, the repeated dose study of 7-MX for 180 days may augment the possibility of using 7-MX clinically for the safe and effective treatment of myopia."	( Sub-chronic and chronic toxicity evaluation of 7-methylxanthine: a new molecule for the treatment of myopia. Jain, SK; Kaur, I; Paul, S; Sahajpal, NS; Singh, H, 2022)	0.72
" Caffeine potentiates the lethality of cells in conjunction with several other stressors such as oxidants, irradiation, and various toxic compounds through largely unknown mechanisms."	( Pleiotropic Effects of Caffeine Leading to Chromosome Instability and Cytotoxicity in Eukaryotic Microorganisms. Chung, WH, 2021)	1.84
"This case describes the interaction between a common caffeine-containing beverage and a commonly prescribed antipsychotic medication, associated with severe adverse effects."	( Caffeine-clozapine interaction associated with severe toxicity and multiorgan system failure: a case report. Peisah, C; Yartsev, A, 2021)	2.31
"Preterm infants are at greater risk for adverse drug effects due to hepatic immaturity."	( Caffeine disrupts ataxia telangiectasia mutated gene-related pathways and exacerbates acetaminophen toxicity in human fetal immortalized hepatocytes. Bandi, S; Gupta, P; Gupta, S; Maisuradze, L; Sharma, Y; Viswanathan, P, 2021)	2.06
" No serious adverse events/deaths were reported."	( Napabucasin Drug-Drug Interaction Potential, Safety, Tolerability, and Pharmacokinetics Following Oral Dosing in Healthy Adult Volunteers. Brantley, SJ; Dai, X; Goulet, MT; Hard, ML; Hitron, M; Karol, MD; McLaughlin, CF, 2021)	0.62
" Many toxic effects are attributed to oxidative damage, and nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical intracellular regulator of the oxidative stress response."	( Caffeine-induced neurotoxicity mediated by Nrf2 pathway in PC12 cells and zebrafish larvae. Chen, WS; Chian, S; Fan, YX; Jiang, LX; Jiang, ZC; Liao, T; Wang, KT; Yao, WX, 2022)	2.16
"Epidemiological studies revealed that prenatal caffeine exposure (PCE) is associated with adverse gestational outcomes and susceptibility to chronic diseases in offspring, yet the effects of PCE on glomerulosclerosis susceptibility in adult female offspring and its intergenerational transmission remain to be further investigated."	( Prenatal caffeine exposure induced renal developmental toxicity and transgenerational effect in rat offspring. Ao, Y; Hu, S; Li, B; Sun, Z; Wang, H; Xia, Z; Xiong, Y; Zhao, X, 2022)	1.4
" Serious adverse events from supplements with these ingredients are rare and typically involve unusually high intakes."	( Dietary Supplements for Weight Management: A Narrative Review of Safety and Metabolic Health Benefits. Blumberg, JB; Chen, O; Liska, DJ; Mah, E, 2022)	0.72
" The adverse effects of the compound on rats and beagle dogs mainly included anorexia and liver function impairment."	( Evaluation of subchronic toxicity of the compound of diphenhydramine hydrochloride and caffeine after 28 days of repeated oral administration in Sprague-Dawley rats and beagle dogs. Chen, J; Chen, Y; Dai, X; Gao, F; Geng, B; Gu, J; Li, J; Mao, J; Ren, L; Shi, W; Tian, Y; Wang, H; Yan, L; Zhang, J; Zhang, T; Zhang, X; Zhu, J, 2023)	1.13
" However, with its increasing popularity, numerous cases of adverse events related to synephrine use have been reported."	( Review of Case Reports on Adverse Events Related to Pre-workout Supplements Containing Synephrine. de Jonge, MLL; Egberink, LB; Kieviet, LC; Sierts, M; van der Heyden, MAG, 2023)	0.91
" The study revealed that caffeine pollution can have adverse effects on marine and offshore ecosystems."	( Development of a trace quantitative method to investigate caffeine distribution in the Yellow and Bohai Seas, China, and assessment of its potential neurotoxic effect on fish larvae. Li, K; Li, Y; Lin, A; Lu, Z; Niu, D; Tang, J; Yan, Z; Yang, X; Zhang, H; Zhang, T; Zhao, J; Zhao, X, 2023)	1.46

Pharmacokinetics

Quinolone is reported to interact with caffeine, often resulting in an increase both in the plasma half-life and AUC. This study sought to assess the pharmacokinetic (PK) changes of caffeine and its CYP1A2 metabolites across the 3 trimesters of pregnancy.

Excerpt	Reference	Relevance
"The pharmacokinetic profile of caffeine was studied in 32 premature newborn infants with apnea: 12 following a single intravenous dose; 3 after a single oral dose; 7 during treatment with an initial empirical (high) maintenance dose schedule; and 10 during treatment with a revised (lower) dose schedule."	( Pharmacokinetic profile of caffeine in the premature newborn infant with apnea. Aldridge, A; Aranda, JV; Collinge, JM; Cook, CE; Gorman, W; Loughnan, PM; Neims, AH; Outerbridge, EW, 1979)	0.84
"h) and terminal-phase half-life (9."	( Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine. Fuhr, U; Granneman, GR; Kinzig, M; Mahr, G; Muth, P; Nickel, P; Patterson, K; Sörgel, F; Stephan, U, 1992)	0.52
" The pharmacokinetic profile of caffeine in the suckling pup following iv bolus administration (5 mg/kg) was more prolonged compared with adult rabbits."	( Pharmacokinetics of caffeine and its demethylated metabolites in lactating adult rabbits and neonatal offspring. Predictions of breast milk to serum concentration ratios. Burgio, D; McNamara, PJ; Yoo, SD, )	0.74
" The relevance of the observed pharmacokinetic phenomena in serum is questionable for the CNS processes because animals convulsed late (starting 90 min) and no significant changes of brain levels of 1 were observed."	( Pharmacodynamic interactions between isoniazid and theophylline in mice and rats, and the influence of pyridoxine. Desta, Z; Steingruber, M, 1992)	0.28
" The differences in pharmacokinetic parameters were not statistically significant among administration routes."	( Pharmacokinetics of caffeine and its metabolites in horses after intravenous, intramuscular or oral administration. Aramaki, S; Ishidaka, O; Momose, A; Suzuki, E; Umemura, K, 1991)	0.6
" The range of clinically acceptable variation in the pharmacokinetic characteristics of drug A defines the equivalence range."	( Lack of pharmacokinetic interaction as an equivalence problem. Hartmann, M; Huber, R; Radtke, HW; Steinijans, VW, 1991)	0.28
"The pharmacokinetic and pharmacodynamic interaction between caffeine and phenylpropanolamine has been investigated in six normal subjects in a double-blind, placebo-controlled, Latin-square design study."	( A pharmacodynamic interaction between caffeine and phenylpropanolamine. Branch, RA; Brown, NJ; Ryder, D, 1991)	0.79
"The pharmacokinetic profile of caffeine was studied in 15 premature infants."	( Pharmacokinetic aspects of caffeine in premature infants. Carnevale, A; Chiarotti, M; De Carolis, MP; De Giovanni, N; Muzii, U; Romagnoli, C; Tortorolo, G, 1991)	0.86
" Therefore, caffeine is maximally effective in potentiating the effect of analgesics at a dose of 10 mg/kg and this potentiation is not due to a pharmacokinetic interaction with the analgesic, and also not due to phosphodiesterase (PDE) inhibition."	( Determination of the optimal analgesia-potentiating dose of caffeine and a study of its effect on the pharmacokinetics of aspirin in mice. Gayawali, K; Pandhi, P; Sharma, PL, 1991)	0.9
"Quinolone is reported to interact with caffeine, often resulting in an increase both in the plasma half-life and AUC, a decrease in total plasma clearance, and little change in the absorption rate constant and maximum plasma level."	( Pharmacokinetic determination of relative potency of quinolone inhibition of caffeine disposition. Barnett, G; Carbó, M; de la Torre, R; Segura, J, 1990)	0.78
" There were no significant alterations of bromocriptine pharmacokinetic parameters after caffeine, although statistical power was very low."	( Pharmacokinetic evaluation of erythromycin and caffeine administered with bromocriptine. Berchou, RC; Kareti, D; LeWitt, PA; Nelson, MV, 1990)	0.76
" The pharmacokinetic behavior is likely to be dominated by a zero dimensional point attractor so that it is highly predictable."	( Pharmacokinetics from a dynamical systems point of view. de Bie, JE; Teeuwen, HW; van Lingen, G; van Rossum, JM, 1989)	0.28
" The pharmacokinetic properties that presumably contribute to self-administration and drug abuse include rapid delivery of the drug into the central nervous system and high free drug clearance."	( Clinical pharmacokinetics of non-opiate abused drugs. Bendayan, R; Busto, U; Sellers, EM, 1989)	0.28
" Other pharmacokinetic parameters of the salicylate remained unchanged."	( Effect of caffeine on the bioavailability and pharmacokinetics of aspirin. Thithapandha, A, 1989)	0.68
"001) and no significant differences were observed in the pharmacokinetic data derived from the respective concentration-time curves."	( The pharmacokinetics of caffeine and its dimethylxanthine metabolites in patients with chronic liver disease. Chakraborty, J; Marks, V; Morgan, MY; Scott, NR; Stambuk, D, 1989)	0.58
"The pharmacokinetic of paraxanthine, one of the primary metabolites of caffeine, is described for the first time."	( Pharmacokinetics of paraxanthine, one of the primary metabolites of caffeine, in the rat. Bonati, M; Bortolotti, A; Jiritano, L, )	0.6
" For a structure-pharmacokinetic relationship study, correlations were found between the partition coefficient and some pharmacokinetic parameters, suggesting that for drugs that are widely metabolized, any predictions of their disposition from physicochemical characteristics are hazardous."	( Correlation between n-octanol/water partition coefficient and liquid chromatographic retention for caffeine and its metabolites, and some structure-pharmacokinetic considerations. Bonati, M; Gaspari, F, 1987)	0.49
" A three-compartment pharmacokinetic model used to stimulate mass transfer from the surface (C1), diffusion through epidermis and dermis (C2), and transfer into the capillary perfusate (C3), was developed based on flux through the IPPSF from 0 to 8 hr."	( The isolated perfused porcine skin flap. III. Percutaneous absorption pharmacokinetics of organophosphates, steroids, benzoic acid, and caffeine. Carver, MP; Riviere, JE; Williams, PL, 1989)	0.48
"1 mg caffeine according to conventional pharmacokinetic methods (Cl = D/AUC)."	( [One point determination of oral caffeine clearance in patients with liver diseases]. Brachtel, D; Epping, J; Hofstetter, G; Joeres, R; Junggeburth, J; Klinker, H; Richter, E; Zilly, W, 1988)	1.07
" It was found that the half-life of all the drugs increased and plasma clearance decreased."	( [Pharmacokinetic characteristics of drugs in experimental splenectomy]. Ashirmetov, AKh; Krakovskiĭ, ME, )	0.13
"The pharmacokinetic and dynamic interactions of caffeine and diazepam after single doses were investigated in six young healthy adults."	( Pharmacokinetic and pharmacodynamic interactions between caffeine and diazepam. Chiang, CK; Ghoneim, MM; Hinrichs, JV; Loke, WH, 1986)	0.77
"The pharmacokinetic parameters of caffeine were measured in 9 pregnant women and 4 women 4 days post partum."	( Pharmacokinetics of caffeine during and after pregnancy. Berland, M; Brazier, JL; Faucon, G; Khenfer, D; Ritter, J, 1983)	0.87
"For psychopharmacological studies with caffeine two reliable non-invasive methods are available in order to determine pharmacokinetic parameters simultaneously with psychometric tests, without any appreciable impairment of the experimental subject."	( [Significance of caffeine values in serum, saliva and urine--determination of pharmacokinetic data by non-invasive methods in psychopharmacologic studies]. Banditt, P; Köhler, E; Walther, H, 1983)	0.87
" Plasma concentrations of the drug peaked at 10 micrograms/ml and decreased rapidly at first, and then more slowly, with an apparent beta-phase half-life of 18."	( Pharmacology, pharmacokinetics, and behavioral effects of caffeine in horses. Greene, EW; Tobin, T; Woods, WE, 1983)	0.51
" The mean maternal and fetal caffeine concentrations were simultaneously evaluated with a two-compartment pharmacokinetic model."	( Pharmacokinetic and hemodynamic effects of caffeine in the pregnant sheep. Ayromlooi, J; Errick, JK; Wilson, SJ, 1983)	0.82
" It is suggested that the control of salt and fluid intake and other factors affecting urine flow rate may be a worthwhile endeavor in pharmacokinetic studies of drugs with properties similar to caffeine."	( Relationship between urine flow rate and renal clearance of caffeine in man. Blanchard, J; Sawers, SJ, 1983)	0.7
"The pharmacokinetic behavior of caffeine was compared in a group of eight healthy young men aged 20."	( Comparative pharmacokinetics of caffeine in young and elderly men. Blanchard, J; Sawers, SJ, 1983)	0.83
" An increase of the half-life of elimination of caffeine has been reported during the final weeks of pregnancy."	( The effect of pregnancy on the pharmacokinetics of caffeine. Knutti, R; Rothweiler, H; Schlatter, C, 1982)	0.77
" Conversely, none of the caffeine pharmacokinetic parameters evaluated changed significantly during the study."	( The effect of vitamin C on the pharmacokinetics of caffeine in elderly men. Blanchard, J; Conrad, KA; Harrison, GG; Trang, JM, 1982)	0.82
" 3 A significant reduction occurred in the systemic clearance of caffeine and the half-life was prolonged as determined from measurement of caffeine in plasma and saliva."	( Decreased systemic clearance of caffeine due to cimetidine. Broughton, LJ; Rogers, HJ, 1981)	0.78
" The mean plasma half-live of theophylline was 22."	( [Pharmacokinetics of theophylline and caffeine in premature infants with apnea (author's transl)]. Lipowsky, G; Riechert, M; Stiegler, H; Stöckl, H, 1981)	0.53
" Despite significant inter-individual differences in pharmacokinetic parameters there was good reproducibility within 5 subjects given 300 mg caffeine orally on 3 occasions."	( Plasma and salivary pharmacokinetics of caffeine in man. Bradbrook, ID; Broughton, LJ; Lind, MJ; Morrison, PJ; Newton, R; Rogers, HJ, 1981)	0.73
"To study the pharmacokinetic interactions between aspirin (250 mg/kg) and simultaneously administered oral acetaminophen (125 mg/kg) or caffeine (50 mg/kg) in male rats, noninterfering GLC assays for these drugs were developed."	( Interactions of aspirin with acetaminophen and caffeine in rat stomach: pharmacokinetics of absorption and accumulation in gastric mucosa. Jager, LP; Olling, M; Seegers, JM; Van Noordwijk, J, 1980)	0.72
"The influence of caffeine (60 mg) was studied on the pharmacokinetic characteristics of acetaminophen (500 mg single dose) in ten healthy male human volunteers in a complete cross-over design."	( The effect of caffeine on the pharmacokinetics of acetaminophen in man. Ahmad, B; Gilani, AU; Iqbal, N; Janbaz, KH; Niazi, SK, 1995)	0.99
"Caffeine elimination half-life (T1/2) and clearance (CLo) were similar in obese and lean subjects (6."	( Caffeine pharmacokinetics in obesity and following significant weight reduction. Berry, EM; Caraco, Y; Levy, M; Zylber-Katz, E, 1995)	3.18
" The ka and Cmax values for theophylline were significantly decreased, and the tmax was significantly increased."	( Influences of immobilization and footshock stress on pharmacokinetics of theophylline and caffeine in rats. Eto, K; Furuno, K; Gomita, Y; Oishi, R; Okazaki, M, 1995)	0.51
"For food-limited rats, serum caffeine was proportional to IP caffeine doses (10-40 mg/kg) for Cmax and area under the curve [AUC(0-24 h)], whereas the three dimethylxanthine (DMX) metabolites of caffeine were disproportional over the dose range."	( Oral and IP caffeine pharmacokinetics under a chronic food-limitation condition. Falk, JL; Lau, CE; Ma, F, 1995)	0.96
" There were significant changes in caffeine plasma half-life (6."	( The influence of rifampin treatment on caffeine clearance in healthy man. Generet, K; Marschall, HU; Matern, S; Wietholtz, H; Zysset, T, 1995)	0.84
"The pharmacokinetic properties of intravenously administered caffeine were studied in 10 horses using a commercially available automated enzyme immunoassay."	( Caffeine clearance in the horse. DeGraves, FJ; Duran, SH; Ruffin, DC; Schumacher, J; Spano, JS; Wilson, RC, 1994)	1.97
" After acute cola administration, we observed an increase in half-life elimination of caffeine and a stabilization of its plasma/erythrocyte ratio."	( Effects of a subacute treatment in rats by a fresh cola extract on EEG and pharmacokinetics. Balansard, G; Jadot, G; Vaille, A, 1993)	0.51
" The half-life of equilibration of effect with plasma caffeine concentration is about 20 minutes."	( Pharmacokinetic-pharmacodynamic modeling of caffeine: tolerance to pressor effects. Benowitz, NL; Denaro, CP; Sheiner, LB; Shi, J, 1993)	0.8
" A pharmacokinetic study was conducted to quantitate changes in the formation clearance (Cl(f)) of NAPQI to assess in vivo the activation and inhibition of NAPQI formation by methylxanthines."	( Effects of caffeine and theophylline on acetaminophen pharmacokinetics: P450 inhibition and activation. Lee, CA; Lillibridge, JH; Nelson, SD; Slattery, JT, 1996)	0.68
" The pharmacokinetic calculations in men demonstrated an interaction between paracetamol and caffeine which was indicated by a decrease in plasma paracetamol levels, by a smaller surface under the curve of changes of paracetamol levels indicating faster elimination of the drug after simultaneous administration with caffeine."	( [Influence of caffeine on toxicity and pharmacokinetics of paracetamol]. Raińska-Giezek, T, 1995)	0.87
"Pharmacokinetic and pharmacodynamic responses to caffeine (2."	( Pharmacokinetic and pharmacodynamic responses to caffeine in poor and normal sleepers. Ashton, H; Kamali, F; Marsh, R; Tiffin, P, 1995)	0.8
" The population pharmacokinetic parameter estimates were then tested prospectively in a further 20 neonates."	( Population pharmacokinetics of caffeine in neonates and young infants. Kerr, S; Thomson, AH; Wright, S, 1996)	0.58
" Elimination half-life was significantly prolonged in the patient group (3."	( Caffeine clearance test: a quantitative liver function assessment in patients with liver cirrhosis. Lee, SD; Lo, KJ; Lu, RH; Shyu, JK; Wang, YJ, 1996)	1.74
" 230 l), and the half-life was slightly increased (19."	( Influence of age, frailty and liver function on the pharmacokinetics of brofaromine. Antonin, KH; Bergmann, W; Bieck, P; Degel, F; Fuchs, L; Platt, D; Zeeh, J, 1996)	0.29
" The half-life of caffeine elimination from blood was seven times longer in the CYP1A2 -/- than wild-type mice."	( Role of CYP1A2 in caffeine pharmacokinetics and metabolism: studies using mice deficient in CYP1A2. Buters, JT; Gelboin, HV; Gonzalez, FJ; Kimura, S; Pineau, T; Tang, BK, 1996)	0.96
"In the present study we have investigated the use of caffeine, administered in the form of instant coffee, as a prodrug for 1MX to validate the use of the 1MU:1MX ratio following caffeine administration as a pharmacodynamic measure of oxypurinol effect on xanthine oxidase."	( 1-Methylxanthine derived from caffeine as a pharmacodynamic probe of oxypurinol effect. Birkett, DJ; Day, RO; Lillywhite, KJ; Miners, JO; Valente, L, 1997)	0.84
" The sigmoid maximal effect-link pharmacodynamic model indicated that caffeine did not alter the concentration at half of the maximal effect value of alprazolam and suggested that the interaction is not competitive, but independent."	( Differential reinforcement of low rate performance, pharmacokinetics and pharmacokinetic-pharmacodynamic modeling: independent interaction of alprazolam and caffeine. Falk, JL; Lau, CE; Wang, Y, 1997)	0.73
" Population pharmacokinetic modeling was performed with NONMEM."	( Population pharmacokinetics of intravenous caffeine in neonates with apnea of prematurity. Charles, B; Flenady, V; Lee, TC; Shearman, A; Steer, P, 1997)	0.56
"To determine population pharmacokinetic parameters of caffeine in premature neonates."	( Population pharmacokinetics of caffeine in premature neonates. Delgado Iribarnegaray, MF; Dominguez-Gil, A; Falcão, AC; Fernández de Gatta, MM; García, MJ; Lanao, JM; Santos Buelga, D, 1997)	0.83
"In this study, which involved on average only two serum concentrations of caffeine per patient, the use of NONMEM gave us significant and consistent information about the pharmacokinetic profile of caffeine when compared with available bibliographic information."	( Population pharmacokinetics of caffeine in premature neonates. Delgado Iribarnegaray, MF; Dominguez-Gil, A; Falcão, AC; Fernández de Gatta, MM; García, MJ; Lanao, JM; Santos Buelga, D, 1997)	0.81
" The serum concentration-time curves for each animal were analyzed separately to estimate model-independent pharmacokinetic variables."	( Comparative pharmacokinetics of caffeine and three metabolites in clinically normal horses and donkeys. Matthews, NS; Mealey, KL; Peck, K; Taylor, TS, 1997)	0.58
"Mean pharmacokinetic values for caffeine, theophylline, and paraxanthine did not differ significantly in horses, compared with donkeys."	( Comparative pharmacokinetics of caffeine and three metabolites in clinically normal horses and donkeys. Matthews, NS; Mealey, KL; Peck, K; Taylor, TS, 1997)	0.86
"This study attempted to compare the pharmacokinetic parameters of caffeine in patients with chronic liver disease and in normal subjects and to define the two sampling times which are suitable for determining caffeine clearance in these patients."	( Caffeine clearance by two point analysis: a measure of liver function in chronic liver disease. Israsena, S; Komolmit, P; Thamaree, S; Tongnopnoua, P; Wittayalertpanya, S, 1996)	1.97
" Pharmacokinetic interactions with other drugs have been described but, in some cases, their mechanism is unknown."	( Pharmacokinetic interactions involving clozapine. Taylor, D, 1997)	0.3
"Published trials and case reports relevant to the human metabolism of clozapine and to suspected pharmacokinetic interactions were reviewed."	( Pharmacokinetic interactions involving clozapine. Taylor, D, 1997)	0.3
" Pharmacodynamic measures included oscillometric blood pressure, systolic blood pressure at the toe and arm using a strain gauge technique, stroke volume and cardiac output using bioimpedance cardiography, high-resolution ultrasound to measure brachial arterial diameter and a novel Doppler method to measure blood flow velocity."	( Peripheral vascular effects and pharmacokinetics of the antimigraine compound, zolmitriptan, in combination with oral ergotamine in healthy volunteers. Dixon, RM; Evans, DH; Meire, HB; On, N; Posner, J; Rolan, PE; Watt, H, 1997)	0.3
" Caffeine kinetics were nonlinear, with clearance significantly reduced and elimination half-life prolonged at the 500-mg compared to the 250-mg dose."	( Dose-dependent pharmacokinetics and psychomotor effects of caffeine in humans. Cotreau, MM; Ehrenberg, BL; Goddard, JE; Greenblatt, DJ; Harmatz, JS; Kaplan, GB; Shader, RI, 1997)	1.45
"Simplified pharmacokinetic methods have been used to estimate caffeine clearance in subjects with liver disease."	( Evaluation of pharmacokinetic methods used to estimate caffeine clearance and comparison with a Bayesian forecasting method. Benowitz, NL; Denaro, CP; Jacob, P, 1998)	0.79
"The present study evaluates effect of pharmacokinetic interaction between caffeine (300 mg) in three divided doses with sodium valproate (400 mg) and carbamazepine (200 mg) given as single doses, in normal human volunteers, using a open cross over design."	( Influence of caffeine on pharmacokinetic profile of sodium valproate and carbamazepine in normal human volunteers. David, J; Joseph, T; Kulkarni, C; Vaz, J, 1998)	0.9
"Hepatic impairment does not warrant dose modification of lamivudine based on this single-dose pharmacokinetic study."	( The pharmacokinetics of lamivudine in patients with impaired hepatic function. Breuel, P; Horak, J; Johnson, MA, 1998)	0.3
" This open-label study evaluated the effect of steady-state venlafaxine on CYP1A2-dependent metabolism, as measured by the pharmacokinetic disposition of caffeine, and urinary caffeine metabolite ratios (CMRs)."	( Effect of venlafaxine on CYP1A2-dependent pharmacokinetics and metabolism of caffeine. Albano, D; Amchin, J; Klockowski, PM; Taylor, KP; Zarycranski, W, 1999)	0.73
" Serum concentrations of fluvoxamine, caffeine and paraxanthine were measured and standard pharmacokinetic parameters were calculated."	( Lack of correlation between fluvoxamine clearance and CYP1A2 activity as measured by systemic caffeine clearance. Dahlqvist, R; Hägg, S; Söderström, E; Spigset, O, 1999)	0.79
"05) differences in the pharmacokinetic parameters of caffeine across the menstrual cycle phases."	( The effect of the menstrual cycle on the pharmacokinetics of caffeine in normal, healthy eumenorrheic females. Eddington, ND; Joubert, A; Kamimori, GH; Otterstetter, R; Santaromana, M, 1999)	0.79
"Several statistical regression models and artificial neural networks were used to predict the hepatic drug clearance in humans from in vitro (hepatocyte) and in vivo pharmacokinetic data and to identify the most predictive models for this purpose."	( Combining in vitro and in vivo pharmacokinetic data for prediction of hepatic drug clearance in humans by artificial neural networks and multivariate statistical techniques. Coassolo, P; Lavé, T; Schneider, G, 1999)	0.3
" Values for AUC and Cmax were significantly higher in CLD patients compared with healthy subjects, and the MRT was prolonged in CLD patients."	( Single-dose pharmacokinetics of repaglinide in subjects with chronic liver disease. Christensen, MS; Hatorp, V; Haug-Pihale, G; Walther, KH, 2000)	0.31
" Caffeine pharmacokinetic parameters were dose independent following intravenous doses ranging from 1 to 20 mg/kg."	( Dose independent pharmacokinetics of caffeine after intravenous administration under a chronic food-limited regimen. Lau, CE; Ma, F; Smith, C, 1999)	1.49
" The purpose of this study was to compare the pharmacokinetic parameters of theophylline and caffeine after intravenous administration of aminophylline to seven Korean low-birthweight neonates with apnea to those in other countries."	( Pharmacokinetics of theophylline and caffeine after intravenous administration of aminophylline to premature neonates in Korea. Ahn, HW; Choi, JH; Park, KJ; Shin, WG; Suh, OK, 1999)	0.8
" The elimination half-life (t(1/2)) was 31."	( The pharmacokinetics, metabolism and urinary detection time of caffeine in camels. Abdel Hadi, AA; Alkatheeri, NA; Almuhrami, AM; Barezaig, IM; Boni, NS; Elghazali, M; Wasfi, IA, 2000)	0.55
" The mechanism by which caffeine increases the antinociceptive action of NSAIDs does not appear to include a pharmacokinetic interaction."	( A review of the pharmacokinetic and pharmacodynamic factors in the potentiation of the antinociceptive effect of nonsteroidal anti-inflammatory drugs by caffeine. Castañeda-Hernández, G; Granados-Soto, V, 1999)	0.81
" This might occur with high levels of consumption or as the result of a pharmacokinetic interaction between caffeine and over-the-counter or prescription medications."	( Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Benitez, J; Carrillo, JA, 2000)	0.76
" In the control group no significant differences between the pharmacokinetic parameters of caffeine in 24-25 and 28-29 day-old calves were observed."	( The effect of short-term starvation or water deprivation on caffeine pharmacokinetics in calves. Antoszek, J; Janus, K; Suszycki, S, 2001)	0.77
" The validity of the human kinetic subfactor has been analysed in relation to CYP1A2 metabolism using published in vivo pharmacokinetic parameters selected to reflect chronic exposure (metabolic and total clearances and area under the plasma concentration-time curve: CLm, CL and AUC) and acute exposure (the peak plasma concentration, C(max))."	( Uncertainty factors for chemical risk assessment. human variability in the pharmacokinetics of CYP1A2 probe substrates. Dorne, JL; Renwick, AG; Walton, K, 2001)	0.31
" During the pharmacodynamic study, HR, BT and LA were measured every 10 min by radiotelemetry and analysed by Cosinor."	( Time-of-day dependent pharmacodynamic and pharmacokinetic profiles of caffeine in rats. Bruguerolle, B; Gantenbein, M; Pelissier-Alicot, AL; Schreiber-Deturmeny, E; Simon, N, 2002)	0.55
" Menstrual cycle, gender, and exercise, with or without an additional thermal stress, had no effect on the pharmacokinetic measurements or urine caffeine."	( Effects of exercise and thermal stress on caffeine pharmacokinetics in men and eumenorrheic women. Graham, TE; McLean, C, 2002)	0.78
" Clearance (Cl) was calculated using the equation of Cl = Kel x Vd (Kel = elimination rate constant, Vd = volume of distribution) and half-life was determined using pharmacokinetic analysis."	( Caffeine clearance in patients with hepatocellular carcinoma after transcatheter oily chemoembolization treatment. Janchai, A; Mahachai, V; Tangkijvanich, P; Thong-Ngam, D; Thumvijit, L; Wittayalertpanya, S, 2002)	1.76
" By comparing the pharmacokinetic parameters of theophylline before and after daily treatment with daidzein, the effect of daidzein on the metabolism of theophylline was evident."	( Effect of daidzein on CYP1A2 activity and pharmacokinetics of theophylline in healthy volunteers. Li, HD; Peng, WX; Zhou, HH, 2003)	0.32
" As such, when these stores are saturated, both volume of distribution and clearance can decrease, thus leading to complex pharmacokinetic situations."	( Pharmacokinetics of the dietary supplement creatine. Brazeau, GA; Hochhaus, G; Persky, AM, 2003)	0.32
"Previous pharmacokinetic studies have shown that a number of the quinolones inhibit the metabolism of caffeine."	( Influence of sex on the pharmacokinetic interaction of fleroxacin and ciprofloxacin with caffeine. Kim, MK; Nicolau, D; Nightingale, C, 2003)	0.76
" Plasma and urine concentrations were determined by validated high-performance liquid chromatography procedures and the data were analysed by noncompartmental linear pharmacokinetic methods."	( Influence of sex on the pharmacokinetic interaction of fleroxacin and ciprofloxacin with caffeine. Kim, MK; Nicolau, D; Nightingale, C, 2003)	0.54
" (AUC)(0-24), (AUC)(0- infinity ), terminal half-life and oral clearance were not affected by menthol."	( Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers. Artok, L; Balkan, D; Benowitz, NL; Gelal, A; Guven, H, 2003)	0.63
"To explore the ability of the nonparametric expectation maximisation (NPEM) method of population pharmacokinetic modelling to deal with sparse data in estimating systemic caffeine clearance for monitoring and evaluation of cytochrome P450 (CYP) 1A2 activity."	( Nonparametric expectation maximisation (NPEM) population pharmacokinetic analysis of caffeine disposition from sparse data in adult caucasians: systemic caffeine clearance as a biomarker for cytochrome P450 1A2 activity. Atanasova, I; Bozhinova, K; Dimitrova, V; Terziivanov, D, 2003)	0.74
"Children's risks can differ from those in adults for numerous reasons, one being differences in the pharmacokinetic handling of chemicals."	( Physiologically based pharmacokinetic (PBPK) modeling of caffeine and theophylline in neonates and adults: implications for assessing children's risks from environmental agents. Ginsberg, G; Hattis, D; Russ, A; Sonawane, B, 2004)	0.57
"The primary objectives of the present study were to establish whether there was a pharmacokinetic or pharmacodynamic interaction between the probe drugs caffeine (CYP1A2), tolbutamide (CYP2C9), debrisoquine (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A4), when administered in combination as a cocktail."	( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1. Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004)	0.52
" Blood pressure and blood glucose measurements were used to assess pharmacodynamic interactions."	( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1. Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004)	0.32
"The five probe drugs when coadministered, in this dosing regimen, demonstrated no evidence of either a metabolic or pharmacodynamic interaction that might confound the conclusions drawn during a cocktail study."	( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1. Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004)	0.32
" A comparison is also presented between several methods based on animal pharmacokinetic data, using the same set of proprietary compounds, and it lends further support for the use of this method, as opposed to methods that require the gathering of pharmacokinetic data in laboratory animals."	( Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics. Gao, F; Lombardo, F; Obach, RS; Shalaeva, MY, 2004)	0.32
"As the mechanism involved in the serious adverse effects associated with phenylpropanolamine (PPA) has not yet been clarified, and as PPA in usual cases is not being ingested without other drugs combination, the aim of this study was to characterize the possibility of pharmacokinetic interactions between PPA and most often combined drugs existing in the same dosage."	( Pharmacokinetic interactions between phenylpropanolamine, caffeine and chlorpheniramine in rats. Kaddoumi, A; Nakashima, K; Nakashima, MN; Wada, M, 2004)	0.57
"The stimulant effect of caffeine, as an additive in diacetylmorphine preparations for study purposes, may interfere with the pharmacodynamic effects of diacetylmorphine."	( Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine. Beijnen, JH; de Jonge, ME; den Hoed, R; Hendriks, VM; Huitema, AD; Sparidans, RW; van den Brink, W; van Ree, JM; Zandvliet, AS, 2005)	0.92
"The combination of ephedrine and caffeine has been used in herbal products for weight loss and athletic performance-enhancement, but the pharmacokinetic profiles of these compounds have not been well characterized."	( Mechanistic pharmacokinetic modelling of ephedrine, norephedrine and caffeine in healthy subjects. Benowitz, NL; Csajka, C; Haller, CA; Verotta, D, 2005)	0.84
"The pharmacokinetic model was developed based on the simultaneous modelling using plasma samples gathered from two clinical trials."	( Mechanistic pharmacokinetic modelling of ephedrine, norephedrine and caffeine in healthy subjects. Benowitz, NL; Csajka, C; Haller, CA; Verotta, D, 2005)	0.56
"Human pharmacokinetic parameters are often predicted prior to clinical study from in vivo preclinical pharmacokinetic data."	( Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure. Jolivette, LJ; Ward, KW, 2005)	0.33
"In pharmacokinetic studies of hepatic impairment, including all classes of cirrhosis may be more revealing than including only selected classes of liver failure."	( Pharmacokinetics of levetiracetam in patients with moderate to severe liver cirrhosis (Child-Pugh classes A, B, and C): characterization by dynamic liver function tests. Brockmöller, J; Coupez, R; Lochs, H; Roots, I; Thomsen, T; Wittstock, M, 2005)	0.33
" Pharmacokinetic data were calculated by a non-compartmental model."	( Effects of Evodia rutaecarpa and rutaecarpine on the pharmacokinetics of caffeine in rats. Chang, CH; Lin, LC; Tsai, TH, 2005)	0.56
"6), and prolonged its elimination half-life (4."	( Fluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics. Culm-Merdek, KE; Greenblatt, DJ; Harmatz, JS; von Moltke, LL, 2005)	0.61
"To determine the pharmacokinetic disposition of IV administered caffeine in healthy Lama spp camelids."	( Pharmacokinetics of intravenously administered caffeine in healthy alpacas (Lama pacos) and llamas (Lama glama). Anderson, DE; Lakritz, J; Linden, DR; Middleton, JR; Sams, RA; Tessman, RK; Tyler, JW, 2006)	0.83
"The present study investigated pharmacokinetic and electroencephalographic responses to caffeine (140 mg) in two groups of healthy volunteers reporting, or not, caffeine-related sleep disturbances."	( Differences in pharmacokinetic and electroencephalographic responses to caffeine in sleep-sensitive and non-sensitive subjects. Arnaud, MJ; Bchir, F; Ben Fradj, R; Dogui, M; Saguem, S, 2006)	0.79
"Prediction of the exposure of neonates, infants and children to xenobiotics is likely to be more successful using physiologically based pharmacokinetic models than simplistic allometric scaling, particularly in younger children."	( Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Johnson, TN; Rostami-Hodjegan, A; Tucker, GT, 2006)	0.33
" In vitro enzyme pharmacokinetic parameters (maximum rate of metabolism [Vmax] and Michaelis-Menten constant [Km]) and in vivo clearance data were obtained from the literature."	( Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Johnson, TN; Rostami-Hodjegan, A; Tucker, GT, 2006)	0.33
"The in silico prediction of pharmacokinetic behaviour in paediatric patients is not intended to replace clinical studies."	( Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Johnson, TN; Rostami-Hodjegan, A; Tucker, GT, 2006)	0.33
" The disposition of TPT did not normalize in UN-ARF rats when treated with caffeine, a non-selective adenosine A1 receptor antagonist, whereas the selective adenosine A1 receptor antagonist (1,3-dipropyl-8-phenylxanthine, DPPX) normalized TPT pharmacokinetic disposition by improving renal function."	( Altered intravenous pharmacokinetics of topotecan in rats with acute renal failure (ARF) induced by uranyl nitrate: do adenosine A1 antagonists (selective/non-selective) normalize the altered topotecan kinetics in ARF? Mullangi, R; Mustafa, S; Pasha, K; Srinivas, NR; Venkatesh, P, 2006)	0.56
" Serial blood samples were collected and pharmacokinetic parameters were estimated using a population pharmacokinetic approach."	( Inhibitory effects of propafenone on the pharmacokinetics of caffeine in humans. Bélanger, PM; Ferron, LA; Gilbert, M; Grech-Bélanger, O; Labbé, L; Michaud, V; Mouksassi, MS; Turgeon, J, 2006)	0.58
" The present study was aimed at building a pharmacokinetic model as a basis for a medical decision support tool."	( Sequential updating of a new dynamic pharmacokinetic model for caffeine in premature neonates. Amzal, B; Bach, V; Bois, FY; Chardon, K; Micallef, S; Tourneux, P, 2007)	0.58
" To take into account the large variability in the population, the pharmacokinetic model is embedded in a population structure."	( Sequential updating of a new dynamic pharmacokinetic model for caffeine in premature neonates. Amzal, B; Bach, V; Bois, FY; Chardon, K; Micallef, S; Tourneux, P, 2007)	0.58
" The update of the pharmacokinetic model using body mass and caffeine concentration data is studied."	( Sequential updating of a new dynamic pharmacokinetic model for caffeine in premature neonates. Amzal, B; Bach, V; Bois, FY; Chardon, K; Micallef, S; Tourneux, P, 2007)	0.82
" The application of the assay to determine the pharmacokinetic disposition after a single oral dose to rats is described."	( Stereospecific determination of cis- and trans-resveratrol in rat plasma by HPLC: application to pharmacokinetic studies. Chen, X; He, H; Ma, L; Ren, W; Wang, G; Yang, B; Yu, Q, 2007)	0.34
" Caffeine partially, but not completely, reversed most pharmacodynamic effects of zolpidem."	( Pharmacokinetic and pharmacodynamic interactions between zolpidem and caffeine. Cysneiros, RM; Farkas, D; Greenblatt, DJ; Harmatz, JS; von Moltke, LL, 2007)	1.48
"Among nonsmokers, the peak concentration (C(max)) and area under concentration-time curve from 0 to infinity [AUC(0-infinity)] of tizanidine did not differ significantly between females and males."	( Effects of gender and moderate smoking on the pharmacokinetics and effects of the CYP1A2 substrate tizanidine. Backman, JT; Neuvonen, PJ; Schröder, MT, 2008)	0.35
" The data were evaluated using a mechanistic pharmacokinetic approach in NONMEM."	( Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin. Cederberg, J; Dahl, ML; Karlsson, MO; Magnusson, MO; Sandström, R, 2008)	0.55
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."	( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Lombardo, F; Obach, RS; Waters, NJ, 2008)	0.35
" Statistics provided no evidence for a true difference in mesalazine pharmacokinetics between slow and rapid acetylators, and no significant correlation between NAT2 activity and any mesalazine pharmacokinetic parameter was found."	( Mesalazine pharmacokinetics and NAT2 phenotype. Fuhr, U; Jetter, A; Kinzig, M; Lück, H; Sörgel, F, 2009)	0.35
" As pharmacokinetic studies in this population are hampered by limitations in the number and volume of plasma samples, we developed an LC-MS/MS assay for the simultaneous determination of these medications in small volume human plasma specimens for pharmacokinetic evaluations in neonates."	( A tandem mass spectrometry assay for the simultaneous determination of acetaminophen, caffeine, phenytoin, ranitidine, and theophylline in small volume pediatric plasma specimens. Budha, NR; Christensen, ML; Mehrotra, N; Meibohm, B; Zhang, Y, 2008)	0.57
"01) in nested models for pharmacokinetic influence."	( Caffeine citrate treatment for extremely premature infants with apnea: population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring. Charles, BG; Flenady, VJ; Gray, PH; Shearman, A; Steer, PA; Townsend, SR, 2008)	1.79
"Caffeine has been shown to maintain or improve the performance of individuals, but its pharmacokinetic profile for Asians has not been well characterized."	( Population pharmacokinetics of caffeine in healthy male adults using mixed-effects models. Fan, W; Fun, CY; Law, YL; Lim, CL; Lim, WM; Seng, KY, 2009)	2.08
"The population pharmacokinetic model satisfactorily described the disposition and variability of caffeine in the data."	( Population pharmacokinetics of caffeine in healthy male adults using mixed-effects models. Fan, W; Fun, CY; Law, YL; Lim, CL; Lim, WM; Seng, KY, 2009)	0.86
" This method can be applied to the pharmacokinetic study of norfloxacin and enoxacin after repeated administration to assess changes in CYP1A2 activity in healthy subjects."	( A simple chromatographic method for determining norfloxacin and enoxacin in pharmacokinetic study assessing CYP1A2 inhibition. Homma, M; Kobayashi, D; Kobayashi, T; Kohda, Y; Momo, K, 2011)	0.37
") decreased metabolism of caffeine to paraxanthine, with overall decrease in caffeine clearance (6-20%), increase in area under the curve (AUC; 7-24%) and plasma half-life (t(1/2) 14-16%)."	( Effects of the aqueous extract from Salvia miltiorrhiza Bunge on caffeine pharmacokinetics and liver microsomal CYP1A2 activity in humans and rats. Wang, X; Yeung, JH, 2010)	0.9
" Pharmacokinetic parameters of CF and its metabolites were calculated."	( Comparative pharmacokinetics and metabolisms of caffeine in sheep breeds. Tras, B; Uney, K, 2011)	0.62
" The aim of this study was to evaluate the pharmacodynamic effects of interactions caused by concomitants in MDMA tablets on extracellular dopamine and serotonin (5-HT) by microdialysis in the striatum of ethylcarbamate-anesthetized rats."	( Pharmacodynamic interactions between MDMA and concomitants in MDMA tablets on extracellular dopamine and serotonin in the rat brain. Fuchigami, Y; Igari, Y; Ikeda, R; Kuroda, N; Nakashima, K; Wada, M, 2011)	0.37
"This was a cross-over pharmacokinetic study in 30 healthy male subjects who received a single oral 100mg caffeine dose after 24-h caffeine abstinence or after maintaining their regular caffeine intake (no caffeine abstinence)."	( Pharmacokinetics of caffeine in plasma and saliva, and the influence of caffeine abstinence on CYP1A2 metrics. Gross, AS; McLachlan, AJ; Perera, V; Xu, H, 2011)	0.91
" Incorporation of the relevant physiological and biochemical changes into predictive bottom-up pharmacokinetic models in order to optimize dosage regimens may offer a logical way forward for the cases where no clinical data exist."	( Application of a systems approach to the bottom-up assessment of pharmacokinetics in obese patients: expected variations in clearance. Aarabi, M; Allabi, AC; Almond, LM; Ghobadi, C; Jamei, M; Johnson, TN; Rostami-Hodjegan, A; Rowland-Yeo, K, 2011)	0.37
"Extension of a mechanistic predictive pharmacokinetic model to accommodate physiological and biochemical changes associated with obesity and morbid obesity allowed prediction of changes in drug clearance on the basis of in vitro data, with reasonable accuracy across a range of compounds that are metabolized by different enzymes."	( Application of a systems approach to the bottom-up assessment of pharmacokinetics in obese patients: expected variations in clearance. Aarabi, M; Allabi, AC; Almond, LM; Ghobadi, C; Jamei, M; Johnson, TN; Rostami-Hodjegan, A; Rowland-Yeo, K, 2011)	0.37
" Therefore, an HPLC-ESI-MS method for simultaneous determination of both drugs, and their metabolites was developed for purpose of pharmacokinetic study."	( An HPLC-ESI-MS method for simultaneous determination of fourteen metabolites of promethazine and caffeine and its application to pharmacokinetic study of the combination therapy against motion sickness. Bai, YQ; Gao, JY; Huang, M; Liang, QL; Luo, GA; Wang, YM; Zhai, ZG, 2012)	0.6
"In the first DDI study, coadministration of ketoconazole (a CYP3A4 inhibitor) and clobazam increased clobazam's area under the concentration time curve from time zero extrapolated to infinity (AUC(0-∞) ) 54% and decreased clobazam's maximum plasma concentration (C(max) ) by 15% versus administration of clobazam alone, but the combination affected these pharmacokinetic parameters for N-CLB to a lesser degree."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
" We have used a pregnancy physiologically based pharmacokinetic (p-PBPK) model to assess the likely impact of pregnancy on three model compounds, namely caffeine, metoprolol and midazolam, based on the knowledge of their disposition in nonpregnant women and information from in vitro studies."	( A pregnancy physiologically based pharmacokinetic (p-PBPK) model for disposition of drugs metabolized by CYP1A2, CYP2D6 and CYP3A4. Abduljalil, K; Gaohua, L; Jamei, M; Johnson, TN; Rostami-Hodjegan, A, 2012)	0.58
"Dried blood spots (DBS) alongside micro-analytical techniques are a potential solution to the challenges of performing pharmacokinetic (PK) studies in children."	( Dried blood spots and sparse sampling: a practical approach to estimating pharmacokinetic parameters of caffeine in preterm infants. Della Pasqua, O; Field, DJ; Gade, S; Kairamkonda, V; Mulla, H; Pandya, HC; Patel, P; Spooner, N, 2013)	0.6
"Predicted metabolic drug clearances (CLPT ) were determined using in vitro-in vivo extrapolation coupled with physiological-based pharmacokinetic modelling and simulation (IVIVE-PBPK) in Simcyp®."	( Predicted metabolic drug clearance with increasing adult age. Doogue, MP; Jensen, BP; Patel, F; Polasek, TM; Sorich, MJ; Wiese, MD, 2013)	0.39
" Here, three different mathematical models were investigated and tested with the experimental data: a pharmacokinetic model (PK), a detailed microscopic two-dimensional diffusion model (MICRO) and a macroscopic homogenized diffusion model (MACRO)."	( Finite dose skin mass balance including the lateral part: comparison between experiment, pharmacokinetic modeling and diffusion models. Hahn, T; Heisig, M; Kostka, KH; Lehr, CM; Naegel, A; Neumann, D; Schaefer, UF; Selzer, D; Wittum, G, 2013)	0.39
" Plasma samples obtained, up to 24 hr after dosing, from four male and four female Microminipigs were analyzed by liquid chromatography tandem mass spectrometry to estimate typical pharmacokinetic parameters for each analyte."	( Simultaneous pharmacokinetics assessment of caffeine, warfarin, omeprazole, metoprolol, and midazolam intravenously or orally administered to Microminipigs. Iwasaki, K; Izumi, H; Kusumoto, S; Mogi, M; Murayama, N; Shimizu, M; Takehara, H; Toda, A; Utoh, M; Yamazaki, H, 2012)	0.64
"We conducted a pharmacokinetic (PK) study and a pharmacodynamic (PD) study to assess whether Roux-en-Y gastric bypass (RYGB) surgery is associated with significant changes to PK and PD of oral medications."	( Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients. Chalasani, N; Hall, SD; Jones, DR; Mattar, S; Tandra, S; Vuppalanchi, R, 2013)	0.39
" Compared with controls, the RYGB group had brisk natriuresis, with significantly lower tmax for urine sodium (1."	( Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients. Chalasani, N; Hall, SD; Jones, DR; Mattar, S; Tandra, S; Vuppalanchi, R, 2013)	0.39
"RYGB recipients have significantly shorter tmax for the studied orally administered medications, but otherwise no other significant changes in PK were reported."	( Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients. Chalasani, N; Hall, SD; Jones, DR; Mattar, S; Tandra, S; Vuppalanchi, R, 2013)	0.39
" Chlorogenic acid-derived metabolites were found to be separated into two groups showing different pharmacokinetic properties."	( Bioappearance and pharmacokinetics of bioactives upon coffee consumption. Beusch, A; Dieminger, N; Dunkel, A; Hauner, H; Hofmann, T; Lang, R; Lee, YM; Skurk, T; Suess, B; Wahl, A, 2013)	0.39
"A new approach for calculation of sample size in pediatric clinical pharmacokinetic studies was suggested based on desired precision for a pharmacokinetic parameter of interest."	( Precision criteria to derive sample size when designing pediatric pharmacokinetic studies: which measure of variability should be used? Aarons, L; Johnson, TN; Ogungbenro, K; Rostami-Hodjegan, A; Salem, F; Vajjah, P, 2014)	0.4
"To evaluate felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions (PK-DDIs) involving cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp)."	( Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions. Doogue, MP; Miners, JO; Polasek, TM; Rowland, A; Snyder, BD, 2014)	0.4
" Blood samples for pharmacokinetic analysis were collected pre-dose and serially for 72 h post-dose."	( Lisdexamfetamine Dimesylate Effects on the Pharmacokinetics of Cytochrome P450 Substrates in Healthy Adults in an Open-Label, Randomized, Crossover Study. Corcoran, M; Ermer, J; Martin, P, 2015)	0.42
" Plasma concentrations of slowly eliminated caffeine and R-/S-warfarin and rapidly eliminated omeprazole and midazolam previously observed in cynomolgus monkeys were scaled to human oral biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model."	( Human plasma concentrations of cytochrome P450 probes extrapolated from pharmacokinetics in cynomolgus monkeys using physiologically based pharmacokinetic modeling. Murayama, N; Shida, S; Shimizu, M; Uno, Y; Utoh, M; Yamazaki, H, 2015)	0.68
"This study sought to assess the pharmacokinetic (PK) changes of caffeine and its CYP1A2 metabolites across the 3 trimesters of pregnancy."	( Pregnancy-induced changes in the pharmacokinetics of caffeine and its metabolites. Campbell, SC; Clark, EA; Schoen, K; Sherwin, CM; Spigarelli, MG; Stockmann, C; Tak, C; Varner, MW; Yu, T, 2016)	0.92
" Because there are some data about the impact of aniseed EO on drug effects, this survey aimed to assess the potential of pharmacokinetic herb-drug interaction between aniseed EO and acetaminophen and caffeine in mice."	( Pharmacokinetic Herb-Drug Interaction between Essential Oil of Aniseed (Pimpinella anisum L., Apiaceae) and Acetaminophen and Caffeine: A Potential Risk for Clinical Practice. Božin, B; Mijatović, V; Petković, S; Samojlik, I; Stilinović, N; Vukmirović, S, 2016)	0.83
" The pharmacokinetic data of cytochrome P450 probes in humans can be extrapolated from corresponding data in cynomolgus monkeys, dogs and minipigs using simplified physiologically based pharmacokinetic (PBPK) modeling."	( Human plasma concentrations of cytochrome P450 probe cocktails extrapolated from pharmacokinetics in mice transplanted with human hepatocytes and from pharmacokinetics in common marmosets using physiologically based pharmacokinetic modeling. Kawano, M; Mitsui, M; Sasaki, E; Shimizu, M; Suemizu, H; Toda, A; Uehara, S; Uno, Y; Utoh, M; Yamazaki, H, 2016)	0.43
" ADRs occur because of interhuman pharmacokinetic variability and interactions with coprescribed medicines."	( Application of a Physiologically Based Pharmacokinetic Model to Study Theophylline Metabolism and Its Interactions With Ciprofloxacin and Caffeine. Lightstone, FC; Navid, A; Ng, DM; Wong, SE, 2016)	0.64
" In this study, we developed a physiologically based pharmacokinetic (PBPK) model using SimCYP to predict the impact of elevated interleukin-6 (IL-6) levels on cytochrome P450 (CYP) enzymes and the treatment effect of an anti-IL-6 monoclonal antibody, sirukumab, in patients with rheumatoid arthritis (RA)."	( Development of a Physiologically Based Pharmacokinetic Model to Predict Disease-Mediated Therapeutic Protein-Drug Interactions: Modulation of Multiple Cytochrome P450 Enzymes by Interleukin-6. Jiang, X; Wang, W; Xu, Z; Zhou, H; Zhuang, Y, 2016)	0.43
"There is a paucity of data describing the impact of type of beverage (coffee versus energy drink), different rates of consumption and different temperature of beverages on the pharmacokinetic disposition of caffeine."	( Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults. Chen, G; Layton, ME; Lazarus, P; Luo, S; McPherson, S; Padowski, JM; White, JR; Zhong, Y, 2016)	0.88
" Caffeine concentration was measured via liquid chromatography-mass spectrometry (LC-MS), and those concentrations were assessed by non-compartmental pharmacokinetic analysis."	( Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults. Chen, G; Layton, ME; Lazarus, P; Luo, S; McPherson, S; Padowski, JM; White, JR; Zhong, Y, 2016)	1.61
" The ANOVA revealed significant differences in mean Cmax and Vd ss/F, but no pair-wise comparisons reached statistical significance."	( Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults. Chen, G; Layton, ME; Lazarus, P; Luo, S; McPherson, S; Padowski, JM; White, JR; Zhong, Y, 2016)	0.7
"The results of this study are consistent with previous caffeine pharmacokinetic studies and suggest that while rate of consumption, temperature of beverage and vehicle (coffee versus energy drink) may be associated with slightly different pharmacokinetic parameters, the overall impact of these variables is small."	( Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults. Chen, G; Layton, ME; Lazarus, P; Luo, S; McPherson, S; Padowski, JM; White, JR; Zhong, Y, 2016)	0.94
"This study sought to assess the pharmacokinetic and pharmacodynamic relationships of caffeine citrate therapy in preterm neonates who had therapeutic drug monitoring (TDM) in the post-extubation period."	( Incorporating pharmacodynamic considerations into caffeine therapeutic drug monitoring in preterm neonates. Balch, AH; Korgenski, EK; Sherwin, CM; Ward, RM; Yu, T, 2016)	0.91
" The relationships between pharmacodynamic effects (heart rate, respiratory rate, episodes of apnea, adverse events) and caffeine serum concentrations were explored."	( Incorporating pharmacodynamic considerations into caffeine therapeutic drug monitoring in preterm neonates. Balch, AH; Korgenski, EK; Sherwin, CM; Ward, RM; Yu, T, 2016)	0.9
"A randomized, single-dose, crossover study assessed hemodynamic and pharmacokinetic effects following 2 days without coffee and caffeine-containing foods."	( Coffee-Antihypertensive Drug Interaction: A Hemodynamic and Pharmacokinetic Study With Felodipine. Arnold, JM; Bailey, DG; Dresser, GK; Freeman, DJ; Urquhart, BL, 2016)	0.64
" Caffeine and felodipine pharmacokinetics were similar for coffee and felodipine given alone or in combination indicating an interaction having a pharmacodynamic basis."	( Coffee-Antihypertensive Drug Interaction: A Hemodynamic and Pharmacokinetic Study With Felodipine. Arnold, JM; Bailey, DG; Dresser, GK; Freeman, DJ; Urquhart, BL, 2016)	1.34
"Blood samples were taken from 21 male and five female individuals, during a 24-h period, to characterize the pharmacokinetic profile of acetaminophen."	( Bioequivalence and Pharmacokinetic Evaluation Study of Acetaminophen vs. Acetaminophen Plus Caffeine Tablets in Healthy Mexican Volunteers. Abarca, JE; Guzmán, NA; Molina, DR; Núñez, BF; Soto-Sosa, JC, 2016)	0.65
" Bariatric surgery resulted in faster absorption and normalized pharmacokinetic parameters, prompting an increase in paracetamol bioavailability."	( Pharmacokinetics in Morbid Obesity: Influence of Two Bariatric Surgery Techniques on Paracetamol and Caffeine Metabolism. Boix, DB; Civit, E; de la Torre, R; Farré, M; Goday Arno, A; Grande, L; Langohr, K; Le Roux, JAF; Lí Carbó, M; Nino, OC; Papaseit, E; Pera, M; Pérez-Mañá, C; Ramon, JM; Rodríguez-Morató, J, 2017)	0.67
" The mean hepatic clearances determined by in silico fitting for individual pharmacokinetic models of warfarin and midazolam in the aged group were, respectively, 23% and 56% smaller than those for the young group."	( Effects of aging and rifampicin pretreatment on the pharmacokinetics of human cytochrome P450 probes caffeine, warfarin, omeprazole, metoprolol and midazolam in common marmosets genotyped for cytochrome P450 2C19. Inoue, T; Kusama, T; Mogi, M; Sasaki, E; Shimizu, M; Toda, A; Uehara, S; Uno, Y; Utoh, M; Yamazaki, H, 2018)	0.7
"Physiologically based pharmacokinetic modeling is considered a valuable tool for predicting pharmacokinetic changes in pregnancy to subsequently guide in-vivo pharmacokinetic trials in pregnant women."	( A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways. Coboeken, K; Dallmann, A; Eissing, T; Hempel, G; Ince, I, 2018)	0.48
"Quantitative information on gestation-specific changes in enzyme activity available in the literature was incorporated in a pregnancy physiologically based pharmacokinetic model and the pharmacokinetics of eight drugs metabolized via one or multiple cytochrome P450 enzymes was predicted."	( A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways. Coboeken, K; Dallmann, A; Eissing, T; Hempel, G; Ince, I, 2018)	0.48
"The pregnancy physiologically based pharmacokinetic model successfully predicted the pharmacokinetics of all tested drugs."	( A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways. Coboeken, K; Dallmann, A; Eissing, T; Hempel, G; Ince, I, 2018)	0.48
"The presented pregnancy physiologically based pharmacokinetic model can quantitatively predict the pharmacokinetics of drugs that are metabolized via one or multiple cytochrome P450 enzymes by integrating prior knowledge of the pregnancy-related effect on these enzymes."	( A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways. Coboeken, K; Dallmann, A; Eissing, T; Hempel, G; Ince, I, 2018)	0.48
" There were no significant differences in the pharmacokinetic parameters of caffeine, omeprazole, metoprolol, chlorzoxazone, and midazolam between the SGI-pretreated and control groups."	( Influence of Shenxiong Glucose Injection on the Activities of Six CYP Isozymes and Metabolism of Warfarin in Rats Assessed Using Probe Cocktail and Pharmacokinetic Approaches. Gong, Z; Huang, J; Li, Y; Liu, C; Liu, T; Lu, Y; Pan, J; Sun, J; Wang, Y; Zheng, J; Zheng, L, 2017)	0.68
"A physiologically based pharmacokinetic (PBPK) model was used to simulate the impact of elevated levels of interleukin (IL)-6 on the exposure of several orally administered cytochrome P450 (CYP) probe substrates (caffeine, S-warfarin, omeprazole, dextromethorphan, midazolam, and simvastatin)."	( Simulating the Impact of Elevated Levels of Interleukin-6 on the Pharmacokinetics of Various CYP450 Substrates in Patients with Neuromyelitis Optica or Neuromyelitis Optica Spectrum Disorders in Different Ethnic Populations. Ducray, PS; Endo-Tsukude, C; Gardner, I; Gill, KL; Hatley, OJ; Machavaram, KK; Parrott, N; Terao, K, 2019)	0.7
" HSB decreased terminal t1/2 and Tmax of caffeine by 13."	( In vitro modulation of cytochrome P450 isozymes and pharmacokinetics of caffeine by extracts of Hibiscus sabdariffa Linn calyx. Adegbolagun, OM; Fakeye, TO; Hokkanen, J; Igbinoba, SI; Kajula, M; Showande, JS; Tolonen, A, 2019)	1.01
" Developing modelling and simulation tools, such as physiologically based pharmacokinetic (PBPK) models that incorporate developmental physiology and maturation of drug metabolism, can be used to predict drug exposure in this group of patients, and may help to optimize drug dose adjustment."	( Preterm Physiologically Based Pharmacokinetic Model. Part II: Applications of the Model to Predict Drug Pharmacokinetics in the Preterm Population. Abduljalil, K; Jamei, M; Johnson, TN; Pan, X; Pansari, A, 2020)	0.56
"This work provides case studies for the pharmacokinetic (PK) analog approach, where a physiologically based pharmacokinetic (PBPK) model for a target chemical (has no PK data) is evaluated using PK data from a source chemical (has existing PK data)."	( Application of structural and functional pharmacokinetic analogs for physiologically based pharmacokinetic model development and evaluation. Ellison, CA; Wu, S, 2020)	0.56
" A physiologically-based pharmacokinetic (PBPK) model was developed integrating in vitro, preclinical, and clinical data of HVs and patients with cancer."	( Ribociclib Drug-Drug Interactions: Clinical Evaluations and Physiologically-Based Pharmacokinetic Modeling to Guide Drug Labeling. Chakraborty, A; Dhuria, SV; Elmeliegy, M; He, H; Heimbach, T; Huth, F; Ji, Y; Miller, M; Samant, TS; Schiller, H; Umehara, K, 2020)	0.56
" Population pharmacokinetic modelling of caffeine in Chinese preterm newborn on a population-wide scale was conducted using NONMEM."	( Developmental population pharmacokinetics of caffeine in Chinese premature infants with apnoea of prematurity: A post-marketing study to support paediatric labelling in China. Gao, XB; Jacqz-Aigrain, E; Jiang, ZH; Ni, SQ; Wang, CH; Wu, YE; Yang, F; Zhao, W; Zheng, Y, 2021)	1.15
" Eight genotypes of CYP1A2 were tested and none of them had a significant impact on caffeine pharmacokinetic parameters."	( Developmental population pharmacokinetics of caffeine in Chinese premature infants with apnoea of prematurity: A post-marketing study to support paediatric labelling in China. Gao, XB; Jacqz-Aigrain, E; Jiang, ZH; Ni, SQ; Wang, CH; Wu, YE; Yang, F; Zhao, W; Zheng, Y, 2021)	1.11
" The aim of this study was to develop and verify a population pharmacokinetic (PPK) model, which can provide a reference for individualized caffeine citrate treatment of apnea in Chinese premature infants."	( Population pharmacokinetic study of caffeine citrate in Chinese premature infants with apnea. Di, X; Fan, J; Guo, A; Hu, X; Huang, L; Xie, H; Xue, J; Zhao, P; Zhu, Z, 2020)	1.03
" The weight at the time of blood collection (CW) and post-natal age were identified as important predictors for pharmacokinetic parameters of caffeine."	( Population pharmacokinetic study of caffeine citrate in Chinese premature infants with apnea. Di, X; Fan, J; Guo, A; Hu, X; Huang, L; Xie, H; Xue, J; Zhao, P; Zhu, Z, 2020)	1.03
"This is a complete PPK study of caffeine citrate in Chinese premature infants with apnea, which complements caffeine pharmacokinetic data of the premature from China."	( Population pharmacokinetic study of caffeine citrate in Chinese premature infants with apnea. Di, X; Fan, J; Guo, A; Hu, X; Huang, L; Xie, H; Xue, J; Zhao, P; Zhu, Z, 2020)	1.12
" dosing, substance, route of application); (iii) pharmacokinetic parameters (e."	( PK-DB: pharmacokinetics database for individualized and stratified computational modeling. Barthorscht, F; Brandhorst, J; De Angelis, S; Duport, Y; Eleftheriadou, D; Green, K; Grzegorzewski, J; Ke, DYJ; Köller, A; König, M, 2021)	0.62
"The plasma elimination half-life of caffeine in the newborn is approximately 100 h."	( Pharmacokinetics, pharmacodynamics and metabolism of caffeine in newborns. Aranda, JV; Beharry, KD, 2020)	1.08
" To estimate the pharmacokinetic parameters, the diabetic animals were assigned to 2 groups: one group received PIO (10 mg/kg), while the other received PIO + caffeine (20 mg/kg)."	( Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats: Impact on therapeutics. Alkahtani, SA; Alshabi, AM; Habeeb, MS; Shaikh, IA, 2021)	2.26
" Although multiple small studies have reported the efficacy of doxapram, the structural co-treatment with caffeine impedes to ascribe the efficacy to doxapram itself or to a pharmacokinetic (PK) interaction where doxapram increases the exposure to caffeine."	( The Pharmacokinetics of Caffeine in Preterm Newborns: No Influence of Doxapram but Important Maturation with Age. Engbers, AGJ; Flint, RB; Knibbe, CAJ; Koch, BCP; Poets, CF; Reiss, IKM; Simons, SHP; Völler, S, 2021)	1.14
" However, varying oxygen environments, such as Hx or neonatal IH, may alter and modify pharmacodynamic actions of caffeine and may even override the benefits caffeine."	( Pharmacodynamic Effects of Standard versus High Caffeine Doses in the Developing Brain of Neonatal Rats Exposed to Intermittent Hypoxia. Ahmad, T; Aranda, JV; Beharry, KD; Cai, CL; Hand, I; Soontarapornchai, K, 2021)	1.09
"This pharmacokinetic (PK) drug-interaction trial investigated the effects of repeated dosing of a plant-derived pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex in the United States and Epidyolex in Europe; 100 mg/mL oral solution) on caffeine clearance via modulation of cytochrome P450 (CYP) 1A2 activity in healthy adults."	( A Phase 1 Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Trial to Investigate the Effect of Cannabidiol on the CYP1A2 Probe Caffeine in Healthy Subjects. Critchley, D; Tayo, B; Thai, C, 2021)	1
"Physiologically based pharmacokinetic (PBPK) models have been proposed as a tool for more accurate individual pharmacokinetic (PK) predictions and model-informed precision dosing, but their application in clinical practice is still rare."	( Data-driven personalization of a physiologically based pharmacokinetic model for caffeine: A systematic assessment. Blank, LM; Burghaus, R; Fendt, R; Hofmann, U; Kerb, R; Kuepfer, L; Lippert, J; Schaeffeler, E; Schlender, JF; Schneider, ARP; Schwab, M; Yilmaz, A, 2021)	0.85
" Deuteration can potentially alter the metabolic profile of a substance, while maintaining its pharmacodynamic properties."	( Pharmacokinetic, pharmacological, and genotoxic evaluation of deuterated caffeine. Burdock, GA; Parente, RM; Sippy, BC; Tarantino, PM, 2022)	0.95
"In this pharmacokinetic simulation study, we generated the body weights (0-49 days of postnatal age [PNA]) of neonates <28 weeks gestational age with different birth weights (550, 750, and 1050 g)."	( Caffeine dosing in premature neonates: impact of birth weight on a pharmacokinetic simulation study. Johnson, PN; Lim, SY; May, CB; Miller, JL, 2023)	2.35
"The half-life decreased and the weight-adjusted clearance increased more significantly in neonates with lower birth weights, resulting in lower caffeine plasma concentrations."	( Caffeine dosing in premature neonates: impact of birth weight on a pharmacokinetic simulation study. Johnson, PN; Lim, SY; May, CB; Miller, JL, 2023)	2.55
"A simple, sensitive, and selective first derivative synchronous fluorimetric method was developed and optimized to track the influence of caffeine content in beverages on the pharmacokinetic parameters of three pharmaceuticals used in relieving headache namely, aspirin (ASP), ibuprofen (IBU), and ergotamine tartrate (ERG)."	( Tracing the influence of caffeine on the pharmacokinetic parameters of three headache relieving pharmaceuticals applying synchronous fluorescence spectroscopy. Draz, ME; El Enany, N; El Sherbiny, D; Wahba, MEK, 2022)	1.23
" The aims of this study were to develop and evaluate population pharmacokinetic (PPK) models of caffeine in preterm infants through comprehensive screening of covariates and then to propose model-informed precision dosing of caffeine for this population."	( Population pharmacokinetic modeling of caffeine in preterm infants with apnea of prematurity: New findings from concomitant erythromycin and AHR genetic polymorphisms. Chen, F; Cheng, R; Dai, HR; Ding, XS; Guo, HL; He, X; Hu, YH; Jiao, Z; Liu, Y; Lu, KY; Xu, J, 2022)	1.21
" This study aimed to build a physiologically based pharmacokinetic (PBPK) model reflecting observed changes in physiological and molecular parameters relevant to drug disposition that are associated with MAFLD."	( A Physiologically Based Pharmacokinetic Model to Predict the Impact of Metabolic Changes Associated with Metabolic Associated Fatty Liver Disease on Drug Exposure. Newman, EM; Rowland, A, 2022)	0.72
" Pharmacokinetic characteristics of probe drugs were subsequently assessed in a Phase I, open-label, single-sequence crossover study in healthy male participants."	( Pharmacokinetic-Interactions of BI 425809, a Novel Glycine Transporter 1 Inhibitor, With Cytochrome P450 and P-Glycoprotein Substrates: Findings From In Vitro Analyses and an Open-Label, Single-Sequence Phase I Study. Chan, T; Desch, M; Hohl, K; Ishiguro, N; Keller, S; Liesenfeld, KH; Müller, F; Schlecker, C; Wind, S; Wunderlich, G, )	0.13
" With BI 425809, area under the plasma concentration curve from administration to the last measurement (AUC 0-tz ) and maximum plasma concentration ( Cmax ) for midazolam were lower than when administered alone."	( Pharmacokinetic-Interactions of BI 425809, a Novel Glycine Transporter 1 Inhibitor, With Cytochrome P450 and P-Glycoprotein Substrates: Findings From In Vitro Analyses and an Open-Label, Single-Sequence Phase I Study. Chan, T; Desch, M; Hohl, K; Ishiguro, N; Keller, S; Liesenfeld, KH; Müller, F; Schlecker, C; Wind, S; Wunderlich, G, )	0.13
" Pharmacokinetic parameters were estimated by using a noncompartmental method."	( Evaluation of the effect of ritlecitinib on the pharmacokinetics of caffeine in healthy participants. Kaplan, J; Liu, J; O'Gorman, MT; Plotka, A; Purohit, VS; Solan, R; Winton, JA; Wolk, R, 2023)	1.15
"Physiologically based pharmacokinetic modeling could be used to predict changes in exposure during pregnancy and possibly inform medicine use in pregnancy in situations in which there is currently limited or no available clinical PK data."	( Use of Physiologically Based Pharmacokinetic Modeling for Hepatically Cleared Drugs in Pregnancy: Regulatory Perspective. Cole, S; Coppola, P; Kerwash, E, 2023)	0.91
" After cocktail alone or in combination with adavosertib administration, 24-h pharmacokinetic sampling occurred for probe substrates and their respective metabolites paraxanthine, 5-hydroxyomeprazole (5-HO), and 1'-hydroxymidazolam (1'-HM)."	( Phase I study to assess the effect of adavosertib (AZD1775) on the pharmacokinetics of substrates of CYP1A2, CYP2C19, and CYP3A in patients with advanced solid tumors. Ah-See, ML; Edenfield, WJ; Lewis, LD; Li, Y; Mugundu, GM; Nadeau, L; Någård, M; Ottesen, LH; Safran, HP; Strauss, J; Wise-Draper, T, 2023)	0.91

Compound-Compound Interactions

The purpose of this study was to examine the metabolic, lipolytic, and cardiovascular responses to supplementation with p-synephrine alone and in combination with caffeine during resistance exercise. Certain psychotropic drugs when combined with caffeine significantly enhanced the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea in murine leukemia L1210.

Excerpt	Reference	Relevance
"Certain psychotropic drugs when combined with caffeine significantly enhanced the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea in murine leukemia L1210."	( Enhancement of the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea by various psychotropic drugs in combination with caffeine. Cohen, MH, 1975)	0.72
" Within each study, there is no significant difference between the elimination rate constants, areas under the plasma concentration/time curve and percentage excreted in urine for the three components administered alone or in any combination with the other components of Optalidon."	( Drug interactions of the components of Optalidon after oral administration. Guillaume, MF; Kiger, JL; Lavene, D; Longchampt, J, 1976)	0.26
"The effect of caffeine (300 mg/70 kg) on cognitive, perceptual and motor functions was investigated both alone and in combination with ethanol (0."	( The effect of caffeine on human performance, alone and in combination with ethanol. Franks, HM; Hagedorn, H; Hensley, VR; Hensley, WJ; Starmer, GA, 1975)	0.98
" If pentobarbital was the CS and d-amphetamine or nicotine sulfate the US, then after about four drug-drug pairings the pentobarbital CS produced a higher heart rate (HR) than control conditions."	( Drug-drug heart rate conditioning in rats: effective USs when pentobarbital is the CS. Reilly, S; Revusky, S, 1992)	0.28
"Nine patients with osteosarcoma were treated by chemotherapy combined with caffeine and surgery."	( Effect of chemotherapy combined with caffeine for osteosarcoma. Baba, H; Tomita, K; Tsuchiya, H; Ueda, Y; Yasutake, H; Yokogawa, A, 1992)	0.79
"The enhanced effect of CDDP combined with caffeine against P-388 leukemia was investigated."	( [Enhanced effect of intraperitoneal administration of CDDP combined with caffeine against peritoneal metastasis]. Akaike, M; Amano, T; Aoyama, N; Hasuo, K; Imada, T; Noguchi, Y; Rino, Y; Takehana, T; Tsuburaya, A; Yamamoto, Y, 1991)	0.78
" The effects of cocaine alone and in combination with d-amphetamine, caffeine, morphine or delta-9-tetrahydrocannabinol were determined in five male white Carneaux pigeons responding under a multiple fixed-ratio 30, fixed-interval 600 schedule (mult FR FI)."	( The effects of cocaine in combination with other drugs of abuse on schedule-controlled behavior in the pigeon. Evans, EB; Wenger, GR, 1990)	0.51
" We investigated the effect of this new sexual hormone alone and in combination with ethynylestradiol on the elimination of both testdrugs."	( [Effect of a new gestagen--dienogest--and its combination with ethinyl estradiol on the activity of biotransformation reactions]. Balogh, A; Hoffmann, A; Klinger, G; Liewald, S; Liewald, T; Schröder, S; Splinter, FC, 1990)	0.28
"We studied the effects of caffeine alone or in combination with homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenylacetic acid (ASE, NSC 290205) on the frequency of SCEs and lymphocyte proliferation kinetics."	( Synergistic induction of cytogenetic damage by the homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenylacetic acid in combination with caffeine in human lymphocytes in vitro and in Ehrlich ascites tumour cells in vivo. Catsoulacos, P; Dozi-Vassiliades, J; Mourelatos, D; Petrou, C, 1990)	0.78
"A study was performed to determine if the pharmacokinetics of bromocriptine is altered by factors that have been shown to interact with other ergot compounds."	( Pharmacokinetic evaluation of erythromycin and caffeine administered with bromocriptine. Berchou, RC; Kareti, D; LeWitt, PA; Nelson, MV, 1990)	0.54
"Early investigational trials with new quinolone antibiotics revealed two important drug-drug interactions: decreased fluoroquinolone absorption when co-administered with magnesium-aluminum antacids and inhibition of theophylline metabolism."	( Drug-drug interactions with ciprofloxacin and other fluoroquinolones. Polk, RE, 1989)	0.28
"Effects of the adenosine analogs R-N6-phenylisopropyl-adenosine (R-PIA) and 5'-N-ethylcarboxamidoadenosine (NECA), alone and in combination with caffeine, were studied in squirrel monkeys trained to respond under multiple fixed-interval fixed-ratio schedules of reinforcement."	( Effects of adenosine analogs alone and in combination with caffeine in the squirrel monkey. Goldberg, SR; Katz, JL; Prada, JA, 1988)	0.72
"A study on the effect of anti-tumor agents combined with caffeine on sarcoma cells was carried out by clonogenic assay."	( [A study of the effect of anti-tumor agents combined with caffeine on established lines of human osteosarcoma cells and primary cultured human sarcoma cells by clonogenic assay]. Tomita, K; Tsuchiya, H, 1987)	0.76
" The extent of absorption following oral administration of tolfenamic acid is decreased during migraine attacks, irrespectively if the volunteers received caffeine or placebo in combination with the drug."	( Tolfenamic acid in combination with caffeine: absorption during acute migraine. Tokola, RA, 1985)	0.74
" Vitamin A induces cytotoxic effects: in combination with melphalan (MELPH), as can be deduced from the resulted synergism on induction of SCEs, the produced cell division delay and the suppressed mitotic index; in combination with caffeine (CAF), producing synergism on induction of SCEs and suppressing the mitotic index; and in combination with MELPH and CAF, producing cell-cycle delays and reducing the mitotic index."	( Induction of sister-chromatid exchanges and cell-cycle delays in human lymphocytes by vitamin A alone or in combination with melphalan and caffeine. Dozi-Vassiliades, J; Granitsas, A; Mourelatos, D; Myrtsiotis, A, 1985)	0.65
" It is often combined with caffeine in diet preparations and "look-alike" pills."	( Cerebral hemorrhage associated with phenylpropanolamine in combination with caffeine. Asdell, SM; Mueller, SM; Muller, J, )	0.66
" After a dose of 100 mg/kg of caffeine given alone and in combination with 50 mg/kg of theophylline, hepatic GSH levels were decreased by 22."	( Hepatic glutathione and lipid peroxidation in rats treated with theophylline. Effect of dose and combination with caffeine and acetaminophen. Abdel-Meguid, EM; Farag, MM, 1994)	0.79
"Antimicrobials of the fluoroquinolone class are involved in a number of clinically important drug-drug interactions."	( Drug-drug interactions with fluoroquinolones. Marchbanks, CR, )	0.13
"The aim of the study was to investigate whether the analgesic effect of propyphenazone (PROP) was increased when it was administered in combination with caffeine (CAFF)."	( Analgesic effects of propyphenazone in comparison to its combination with caffeine. Hummel, T; Kobal, G; Kraetsch, HG; Kussat, R; Lötsch, J, 1996)	0.72
" No significant differences between plasma levels of PROP were found when applied either alone or in combination with CAFF."	( Analgesic effects of propyphenazone in comparison to its combination with caffeine. Hummel, T; Kobal, G; Kraetsch, HG; Kussat, R; Lötsch, J, 1996)	0.52
"The analgesic drug combination Thomapyrin consisting of acetylsalicylic acid (CAS 50-78-2, ASA), paracetamol (CAS 103-90-2, NAPAP) and caffeine (CAS 58-08-2) in the ratio 5:4:1 was investigated for its chronic toxicity in rats."	( Studies on the chronic oral toxicity of an analgesic drug combination consisting of acetylsalicylic acid, paracetamol and caffeine in rats including an electron microscopical evaluation of kidneys. Bauer, E; Bauer, M; Greischel, A; Hirsch, U; Lehmann, H; Schmid, J; Schneider, P, 1996)	0.7
"The objective of this study was to quantify the analgesic efficacy of paracetamol and its combination with codeine or caffeine through a systematic overview and meta-analysis of relevant randomized controlled trials (RCTs)."	( Analgesic efficacy of paracetamol and its combination with codeine and caffeine in surgical pain--a meta-analysis. Li Wan Po, A; Zhang, WY, 1996)	0.74
" Zolmitriptan, at eight times the likely therapeutic dose, was generally well tolerated both alone and in combination with ergotamine."	( Peripheral vascular effects and pharmacokinetics of the antimigraine compound, zolmitriptan, in combination with oral ergotamine in healthy volunteers. Dixon, RM; Evans, DH; Meire, HB; On, N; Posner, J; Rolan, PE; Watt, H, 1997)	0.3
" Another drug whose mechanism of action is unknown is caffeine, which is often used in combination with other analgesics, augmenting their effect."	( Effects of caffeine and paracetamol alone or in combination with acetylsalicylic acid on prostaglandin E(2) synthesis in rat microglial cells. Aicher, B; Engelhardt, G; Fiebich, BL; Hüll, M; Lieb, K; Pairet, M; van Ryn, J, 2000)	0.95
" To clarify this matter the study investigated the effects of aspirin alone and in combination with caffeine on mood and cardiovascular parameters before, during, and after pain induction through mechanical stimulation."	( [Experimental study of the effect of acetylsalicylic acid combined with caffeine regarding possible abuse potential]. Hüppe, A; Janke, W, 2001)	0.76
"Many fluoroquinolone antibiotics are inhibitors of cytochrome P450 enzyme systems and may produce potentially important drug interactions when administered with other drugs."	( Drug interactions with clinafloxacin. Abel, R; Alvey, CW; Bron, NJ; Hounslow, NJ; Koup, JR; Randinitis, EJ; Rausch, G; Sedman, AJ; Vassos, AB, 2001)	0.31
"Because caffeine and tissue levels of Zn are closely related, the objectives of this study were to determine the changes in plasma caffeine levels over a period of 5 h when different concentrations of Zn combined with a fixed concentration of caffeine were injected into the femoral vein of rats and to determine the relationship between tissue levels of caffeine and Zn at 5 h postinjection."	( Association of different zinc concentrations combined with a fixed caffeine dose on plasma and tissue caffeine and zinc levels in the rat. Gottschalk, S; Ide, K; Nakamoto, T; Yazdani, M, 2002)	0.99
" The efficacy of indomethacin, alone and combined with prochlorperazine and caffeine, in abolishing peripheral and central sensitization in in vivo models of hyperalgesia is a further explanation of the clinical efficacy of IndoProCaf in the treatment of migraine."	( Indomethacin, alone and combined with prochlorperazine and caffeine, but not sumatriptan, abolishes peripheral and central sensitization in in vivo models of migraine. Galeotti, N; Ghelardini, C; Grazioli, I; Uslenghi, C, 2004)	0.8
"This hypothesis was tested in an experiment where information about the effect of a drug was combined with administration of an active drug or placebo."	( Stimulant and relaxant drugs combined with stimulant and relaxant information: a study of active placebo. Aamo, T; Flaten, MA; Olsen, H; Sager, G; Simonsen, T; Zahlsen, K, 2004)	0.32
" Drug eruption due to a drug combination appears to be very rare."	( Multiple fixed drug eruption due to drug combination. Hara, H; Yokoyama, A, 2005)	0.33
" This study assessed the effects of caffeine on sleep architecture and electroencephalography (EEG) spectrum alone and in combination with two different sleep-promoting medications."	( Effects on sleep stages and microarchitecture of caffeine and its combination with zolpidem or trazodone in healthy volunteers. Hutson, PH; Ivarsson, M; Nutt, DJ; Paterson, LM; Wilson, SJ, 2009)	0.88
" Male ICR mice were treated with ketamine alone or ketamine combined with various doses of caffeine, then the locomotor activity, rotarod test, prepulse inhibition of acoustic startle, loss of righting reflex, and mortality rate were examined."	( Behavioural and toxic interaction profile of ketamine in combination with caffeine. Chen, HH; Chiu, PH; Hsu, HR; Mei, YY; Wu, CY, 2009)	0.8
"To determine the risk: benefit of paracetamol combined with caffeine in the short-term management of acute pain conditions."	( A risk-benefit assessment of paracetamol (acetaminophen) combined with caffeine. Day, R; Graham, G; Palmer, H; Williams, K, 2010)	0.84
"Database searches were conducted to identify double-blind trials comparing paracetamol/caffeine with paracetamol alone (benefit analysis) and any data pertaining to hepatotoxicity of paracetamol when combined with caffeine (risk analysis)."	( A risk-benefit assessment of paracetamol (acetaminophen) combined with caffeine. Day, R; Graham, G; Palmer, H; Williams, K, 2010)	0.82
"A method of hollow fiber (HF) liquid phase microextraction (LPME) combined with gas chromatography (GC)-flame ionization detection (FID) was developed for the simultaneous quantification of trace amphetamine (AP), methamphetamine (MA), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), caffeine and ketamine (KT) in drug abuser urine samples."	( Simultaneous quantification of amphetamines, caffeine and ketamine in urine by hollow fiber liquid phase microextraction combined with gas chromatography-flame ionization detector. Chen, J; He, M; Hu, B; Xiong, J, 2010)	0.79
" The drug combination led to more male ambulation than for alcohol alone, and higher occupancy of the center squares of the apparatus than for males in any other group."	( Adult anxiety-related behavior of rats following consumption during late adolescence of alcohol alone and in combination with caffeine. Hughes, RN, 2011)	0.58
"To investigate potential drug-drug interactions between clobazam and cytochrome P450 (CYP) isoenzyme substrates, inhibitors, and inducers."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
"Two, prospective, open-label, single-center, drug-drug interaction (DDI) studies and a population pharmacokinetics analysis of seven multicenter phase II-III trials."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
"Fifty-four healthy adult volunteers were enrolled in the two drug-drug interaction studies; 53 completed the studies."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
"In the first drug-drug interaction study, 36 participants received a single oral dose of clobazam 10 mg on day 1, followed by either ketoconazole 400 mg once/day or omeprazole 40 mg once/day on days 17-22, with a single dose of clobazam 10 mg coadministered on day 22, to study the effects of CYP3A4 or CYP2C19 inhibition, respectively, on clobazam and its active metabolite N-desmethylclobazam (N-CLB)."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
" In the second DDI study, no clinically significant drug-drug interactions were observed between clobazam 40 mg and the CYP probe substrates caffeine or tolbutamide."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.58
"These findings suggest no clinically meaningful drug-drug interactions between clobazam and drugs metabolized by CYP3A4, CYP2C19, CYP1A2, or CYP2C9."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
"This study aims to evaluate the objective and subjective effects of alcohol versus placebo at two alcohol doses, alone and in combination with an energy drink, in a balanced order, placebo-controlled, double-blind design."	( The effects of energy drink in combination with alcohol on performance and subjective awareness. Alford, C; Hamilton-Morris, J; Verster, JC, 2012)	0.38
" Neither breath alcohol concentration nor the subjective measures showed a significant difference between the energy drink and the placebo energy drink when combined with alcohol."	( The effects of energy drink in combination with alcohol on performance and subjective awareness. Alford, C; Hamilton-Morris, J; Verster, JC, 2012)	0.38
"The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions."	( Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. Artursson, P; Haglund, U; Karlgren, M; Kimoto, E; Lai, Y; Norinder, U; Vildhede, A; Wisniewski, JR, 2012)	0.38
" The KNN method in combination with chemical analysis is recommended for discrimination of the production seasons of Chinese green tea."	( Discrimination of the production season of Chinese green tea by chemical analysis in combination with supervised pattern recognition. Li, D; Song, Q; Wan, X; Xu, W, 2012)	0.38
"To evaluate felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions (PK-DDIs) involving cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp)."	( Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions. Doogue, MP; Miners, JO; Polasek, TM; Rowland, A; Snyder, BD, 2014)	0.4
"Estimation of ergogenic effects of caffeine and bitter orange exract combined with alcohol is presented in the article."	( [Comparative analysis of ergogenic efficacy of energy drinks components (caffeine and bitter orange extract) in combination with alcohol]. Anuchin, AM; Iuvs, GG, 2014)	0.91
" Higher sodium alginate concentration (3%) for production of hydrogel beads in combination with psyllium or chitosan coating would present the most favourable carrier systems for immobilization of caffeine."	( Improving the controlled delivery formulations of caffeine in alginate hydrogel beads combined with pectin, carrageenan, chitosan and psyllium. Belščak-Cvitanović, A; Djaković, S; Ježek, D; Karlović, S; Komes, D; Mršić, G; Spoljarić, I, 2015)	0.86
" The hypoglycemic action of JAT was also confirmed: JAT, in combination with acarbose, produced a synergistic inhibitory effect on plasma glucose levels in vivo."	( Inhibitory effect of black tea and its combination with acarbose on small intestinal α-glucosidase activity. Igarashi, M; Satoh, T; Takahashi, N; Watanabe, K; Yamada, S, 2015)	0.42
" Therefore, the purpose of the present study was to examine the effects of supplementation with p-synephrine alone and in combination with caffeine on free-weight resistance exercise performance."	( The effects of supplementation with P-Synephrine alone and in combination with caffeine on resistance exercise performance. Bush, JA; Diamond, KB; Faigenbaum, AD; Kang, J; Kraemer, WJ; Leise, MD; Nocera, VG; Ratamess, NA; Stohs, SJ, 2015)	0.85
" In the current study, stepwise injection analysis (SWIA) was successfully combined with single-drop liquid microextraction (SDLME) and solvent exchange procedure."	( Stepwise injection potentiometric determination of caffeine in saliva using single-drop microextraction combined with solvent exchange. Bulatov, A; Kirsanov, D; Medinskaia, K; Nikolaeva, L; Timofeeva, I, 2016)	0.69
" To further validate this cocktail, in this study, we have verified whether probe drugs contained in the latter cause mutual drug-drug interactions."	( Evaluation of Mutual Drug-Drug Interaction within Geneva Cocktail for Cytochrome P450 Phenotyping using Innovative Dried Blood Sampling Method. Bosilkovska, M; Daali, Y; Déglon, J; Desmeules, J; Samer, C; Thomas, A; Walder, B, 2016)	0.43
"The purpose of this study was to examine the metabolic, lipolytic, and cardiovascular responses to supplementation with p-synephrine alone and in combination with caffeine during resistance exercise (RE)."	( The Effects of Supplementation with p-Synephrine Alone and in Combination with Caffeine on Metabolic, Lipolytic, and Cardiovascular Responses during Resistance Exercise. Bush, JA; Campbell, SC; Diamond, KB; Faigenbaum, AD; Kang, J; Kraemer, WJ; Leise, MD; Miller, HB; Nocera, VG; Ratamess, NA; Stohs, SJ, )	0.55
"This phase 1, open-label, crossover study sought to evaluate drug-drug interactions between tivantinib and cytochrome P450 (CYP) substrates and tivantinib and P-glycoprotein."	( Evaluation of the pharmacokinetic drug interaction potential of tivantinib (ARQ 197) using cocktail probes in patients with advanced solid tumours. Gajee, R; Papadopoulos, KP; Puzanov, I; Strickler, JH; Tachibana, M; Wang, Y; Zahir, H, 2018)	0.48
"The data suggest that tivantinib 360 mg twice daily has either a minimal or no effect on the pharmacokinetics of probe drugs for CYP1A2, CYP2C9, CYP2C19 and CYP3A4 substrates, and decreases the systemic exposure of P-glycoprotein substrates when administered with tivantinib."	( Evaluation of the pharmacokinetic drug interaction potential of tivantinib (ARQ 197) using cocktail probes in patients with advanced solid tumours. Gajee, R; Papadopoulos, KP; Puzanov, I; Strickler, JH; Tachibana, M; Wang, Y; Zahir, H, 2018)	0.48
"The purpose was to examine cardiovascular responses to supplementation with p-synephrine alone and in combination with caffeine during quiet sitting."	( Acute cardiovascular effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine in human subjects: A placebo-controlled, double-blind study. Bush, JA; Ellis, NL; Faigenbaum, AD; Hasan, SB; Kang, J; Kuper, JD; O'Grady, EA; Ratamess, NA; Stohs, SJ; Vought, IT, 2018)	0.9
"To evaluate the capacity for modafinil to be a perpetrator of metabolic drug-drug interactions by altering cytochrome P450 activity following a single dose and dosing to steady state."	( Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions using a model informed cocktail reaction phenotyping trial protocol. Mangoni, AA; Rowland, A; Sorich, MJ; van Dyk, M; Warncken, D, 2018)	0.48
"These data support consideration of the risk of clinically relevant metabolic drug-drug interactions perpetrated by modafinil when this drug is co-administered with drugs that are primarily cleared by CYP2C19 (single modafinil dose or steady state modafinil dosing) or CYP3A4 (steady state modafinil dosing only) catalysed metabolic pathways."	( Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions using a model informed cocktail reaction phenotyping trial protocol. Mangoni, AA; Rowland, A; Sorich, MJ; van Dyk, M; Warncken, D, 2018)	0.48
" The metabolic profile of guarana from the two largest producing regions was investigated using UPLC-MS combined with multivariate statistical analysis."	( Chemical profiling of guarana seeds (Paullinia cupana) from different geographical origins using UPLC-QTOF-MS combined with chemometrics. Canuto, KM; Coutinho, JP; da Silva, GS; de Brito, ES; de Jesus, RM; Nascimento, MM; Ribeiro, PRV; Zocolo, GJ, 2017)	0.46
"This review examines the effects of carbohydrates, delivered individually and in combination with caffeine, on a range of cognitive domains and subjective mood."	( The Effects of Carbohydrates, in Isolation and Combined with Caffeine, on Cognitive Performance and Mood-Current Evidence and Future Directions. Bernard, BN; Louise, D; Louise, LC, 2018)	0.94
"The purpose of this study was to examine acute hematological and mood perception responses to supplementation with p-synephrine alone and in combination with caffeine during quiet sitting."	( Acute hematological and mood perception effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine: A placebo-controlled, double-blind study. Bush, JA; Ellis, NL; Faigenbaum, AD; Kang, J; Kuper, JD; O'Grady, EA; Ratamess, NA; Stohs, SJ; Vought, IT, 2018)	0.88
" We recently reported that recombinant methioninase (rMETase) inhibited SS growth in a patient-derived orthotopic xenograft (PDOX) mouse model and was more effective when administered in combination with the first-line drug doxorubicin (DOX)."	( Oral Recombinant Methioninase Combined with Caffeine and Doxorubicin Induced Regression of a Doxorubicin-resistant Synovial Sarcoma in a PDOX Mouse Model. Chawla, SP; Eilber, FC; Han, Q; Hayashi, K; Higuchi, T; Hoffman, RM; Igarashi, K; Kawaguchi, K; Kimura, H; Miwa, S; Miyake, K; Oshiro, H; Razmjooei, S; Singh, AS; Singh, SR; Sugisawa, N; Tan, Y; Tsuchiya, H; Yamamoto, N; Zhang, Z, 2018)	0.74
" DOX combined with o-rMETase and caffeine led to regression of SS-PDOX."	( Oral Recombinant Methioninase Combined with Caffeine and Doxorubicin Induced Regression of a Doxorubicin-resistant Synovial Sarcoma in a PDOX Mouse Model. Chawla, SP; Eilber, FC; Han, Q; Hayashi, K; Higuchi, T; Hoffman, RM; Igarashi, K; Kawaguchi, K; Kimura, H; Miwa, S; Miyake, K; Oshiro, H; Razmjooei, S; Singh, AS; Singh, SR; Sugisawa, N; Tan, Y; Tsuchiya, H; Yamamoto, N; Zhang, Z, 2018)	1.02
"Electronic nose (E-nose), electronic tongue (E-tongue) and electronic eye (E-eye) combined with chemometrics methods were applied for qualitative identification and quantitative prediction of tea quality."	( The qualitative and quantitative assessment of tea quality based on E-nose, E-tongue and E-eye combined with chemometrics. Wang, J; Xu, M; Zhu, L, 2019)	0.51
"Cytochrome P450 (CYP) downregulation is a mechanism of drug-drug interaction encountered in pharmaceutical development which is difficult to evaluate in vitro because of the scarcity of evidence."	( CYP1A2 Downregulation by Obeticholic Acid: Usefulness as a Positive Control for the In Vitro Evaluation of Drug-Drug Interactions. Ishida, C; Kotake, Y; Sanoh, S, 2019)	0.51
" Recently, using a patient-derived orthotopic xenograft (PDOX) model of malignant soft-tissue sarcoma (STS), we showed that oral recombinant methioninase (o-rMETase), in combination with caffeine, was more efficacious than o-rMETase alone in inhibiting STS tumor growth."	( Oral Recombinant Methioninase, Combined With Oral Caffeine and Injected Cisplatinum, Overcome Cisplatinum-Resistance and Regresses Patient-derived Orthotopic Xenograft Model of Osteosarcoma. Bouvet, M; Chawla, SP; Han, Q; Hayashi, K; Higuchi, T; Hoffman, RM; Igarashi, K; Kimura, H; Miwa, S; Miyake, K; Oshiro, H; Park, J; Razmjooei, S; Singh, SR; Sugisawa, N; Tan, Y; Tsuchiya, H; Yamamoto, N; Zhang, Z, 2019)	0.96
" The probe cocktail was generally well-tolerated when administered in combination with guselkumab in patients with psoriasis."	( Evaluating Potential Disease-Mediated Protein-Drug Interactions in Patients With Moderate-to-Severe Plaque Psoriasis Receiving Subcutaneous Guselkumab. Chen, D; Piantone, A; Sharma, A; Shu, C; Xu, Y; Xu, Z; Zhou, H; Zhu, Y; Zhuang, Y, 2020)	0.56
"Ribociclib is approved in combination with endocrine therapy as initial endocrine-based therapy for HR-positive and HER2-negative advanced breast cancer."	( Ribociclib Drug-Drug Interactions: Clinical Evaluations and Physiologically-Based Pharmacokinetic Modeling to Guide Drug Labeling. Chakraborty, A; Dhuria, SV; Elmeliegy, M; He, H; Heimbach, T; Huth, F; Ji, Y; Miller, M; Samant, TS; Schiller, H; Umehara, K, 2020)	0.56
" Since drug-drug interactions can cause serious adverse effects and impede overall curative effects, evidence regarding the risk associated with drug-drug interactions between Hb-V and such simultaneously administered drugs is needed."	( Assessing cytochrome P450-based drug-drug interactions with hemoglobin-vesicles, an artificial red blood cell preparation, in healthy rats. Ohtsuki, S; Otagiri, M; Sakai, H; Taguchi, K; Tokuno, M; Yamasaki, K, 2020)	0.56
" RNAi therapeutics, such as givosiran, have a low liability for drug-drug interactions (DDIs) because they are not metabolized by cytochrome 450 (CYP) enzymes, and do not directly inhibit or induce CYP enzymes in the liver."	( A Drug-Drug Interaction Study Evaluating the Effect of Givosiran, a Small Interfering Ribonucleic Acid, on Cytochrome P450 Activity in the Liver. Agarwal, S; Clausen, VA; Harper, P; Najafian, N; Robbie, GJ; Sardh, E; Simon, AR; Vassiliou, D, 2021)	0.62
"To explore the application effect of aminophylline combined with caffeine citrate and GMs in the evaluation of neurodevelopmental treatment and follow-up in high-risk preterm infants."	( Aminophylline in combination with caffeine citrate in neurodevelopmental treatment and follow-up of high-risk preterm infants using GMs assessment. Chen, W; Feng, X; Zheng, K, 2022)	1.24
" We assessed the time-dependent biological impact induced by environmental concentrations of caffeine alone (CAF; 5 ng/L to 10 µg/L) and its combination with salicylic acid (CAF+SA; 5 ng/L+0."	( Comparison of cellular mechanisms induced by pharmaceutical exposure to caffeine and its combination with salicylic acid in mussel Mytilus galloprovincialis. Afsa, S; Ben Mansour, H; Billè, B; Cappello, T; De Marco, G; Galati, M; Parrino, V, 2022)	1.17
"To explore the curative effect of "Jiaotai Pill" combined with head rhythmic massage consistent with 5-tone rhythm on insomnia of heart-kidney disharmony type."	( Clinical study of "Jiaotai Pill" combined with head massage with 5-tone rhythm on insomnia patients of heart-kidney disharmony type. Guan, R; Li, J; Liu, Z; Pan, L; Shi, Q; Yu, Z, 2023)	0.91
" Patients in group A were treated with traditional head massage combined with oral estazolam tablets."	( Clinical study of "Jiaotai Pill" combined with head massage with 5-tone rhythm on insomnia patients of heart-kidney disharmony type. Guan, R; Li, J; Liu, Z; Pan, L; Shi, Q; Yu, Z, 2023)	0.91
"The overall efficacy of Jiaotai Pill combined with head massage therapy consistent with 5-tone rhythm is significantly better than that of traditional massage combined with 5-element music therapy for insomnia patients with heart-kidney disharmony."	( Clinical study of "Jiaotai Pill" combined with head massage with 5-tone rhythm on insomnia patients of heart-kidney disharmony type. Guan, R; Li, J; Liu, Z; Pan, L; Shi, Q; Yu, Z, 2023)	0.91
" A2A receptor antagonists are an emerging class of agents that treat cancers by enhancing immunotherapy, both as monotherapy and in combination with other therapeutic agents."	( Caffeine-folic acid-loaded-chitosan nanoparticles combined with methotrexate as a novel HepG2 immunotherapy targeting adenosine A2A receptor downstream cascade. Gaber, M; Ghareeb, D; Hamed, A; Hamed, M; Mohamed, TM; Nofal, MS, 2023)	2.35
"This study suggests that CAF-FA-CS-NPs (D4) in combination with MTX may be a promising candidate for cancer immunotherapy, by inhibiting A2aR signaling and leading to improved immune activation and anti-tumor activity of MTX."	( Caffeine-folic acid-loaded-chitosan nanoparticles combined with methotrexate as a novel HepG2 immunotherapy targeting adenosine A2A receptor downstream cascade. Gaber, M; Ghareeb, D; Hamed, A; Hamed, M; Mohamed, TM; Nofal, MS, 2023)	2.35

Bioavailability

Coffee and trigonelline are some of the most important bioactive organic compounds of these beverages. High solubility and high permeability of caffeine rank it among class I of BCS and well absorbed compounds.

Excerpt	Reference	Relevance
" Based on a pharmacokinetic model, the following conclusions can be drawn: a) There is no change in bioavailability due to the combination of the three components in Optalidon in respect to their single administration."	( Drug interactions of the components of Optalidon after oral administration. Guillaume, MF; Kiger, JL; Lavene, D; Longchampt, J, 1976)	0.26
" Accumulation of caffeine, with its subsequent metabolism to theophylline, in patients, who consume average quantities of caffeine-containing beverages relative to those patients who avoid such drinks could interfere with bioavailability studies in normal volunteers."	( The human metabolism of caffeine to theophylline. Hossie, RD; McGilveray, IJ; Sved, S, 1976)	0.9
" The rate of absorption of caffeine across rat intestine using the everted gut was also compared for a guarana suspension and a solution containing an equivalent amount of caffeine."	( Dissolution and absorption of caffeine from guarana. Bempong, DK; Houghton, PJ, 1992)	0.87
" Our results showed that a hydrophilic compound poorly absorbed (urea) was insensitive to cutaneous blood flow modifications whereas compounds readily absorbed (caffeine, amphiphilic; urea on stripped skin) or slightly absorbed (progesterone, lipophilic) exhibited local concentration phenomena in relation to cutaneous blood flow lowering."	( Importance of blood flow to the local distribution of drugs after percutaneous absorption in the bipediculated dorsal flap of the hairless rat. Auclair, F; Besnard, M; Dupont, C; Wepierre, J, 1991)	0.48
"Quinolone is reported to interact with caffeine, often resulting in an increase both in the plasma half-life and AUC, a decrease in total plasma clearance, and little change in the absorption rate constant and maximum plasma level."	( Pharmacokinetic determination of relative potency of quinolone inhibition of caffeine disposition. Barnett, G; Carbó, M; de la Torre, R; Segura, J, 1990)	0.78
" We conclude that erythromycin can markedly increase the systemic bioavailability of bromocriptine, which can lead to increased therapeutic or adverse effects, whereas the effects of caffeine require further study."	( Pharmacokinetic evaluation of erythromycin and caffeine administered with bromocriptine. Berchou, RC; Kareti, D; LeWitt, PA; Nelson, MV, 1990)	0.73
"The objective of this study was to determine the influence of caffeine on aspirin bioavailability and pharmacokinetics in man."	( Effect of caffeine on the bioavailability and pharmacokinetics of aspirin. Thithapandha, A, 1989)	0.92
" The first-order absorption rate constant (ka) was estimated from the rise in the plasma concentration-time curve and extent of absorption was estimated by the area under the concentration-time curve."	( Effect of formula feeding on oral absorption of caffeine in premature infants. Giacoia, GP; Jungbluth, GL; Jusko, WJ, 1989)	0.53
" The determination of cerebral bioavailability utilizing time- and dose-efficacy relations, as well as the evaluation of bioequipotency of different formulations of compounds is shown."	( Topographic brain mapping of EEG in neuropsychopharmacology--Part II. Clinical applications (pharmaco EEG imaging). Anderer, P; Grünberger, J; Kinsperger, K; Saletu, B, 1987)	0.27
" Since in CF some compounds are poorly absorbed or abnormally metabolized, and the function of salivary glands or renal tubuli partly impaired, caffeine was measured in urine, blood, and saliva after a single oral dose of 3 mg/kg in CF patients."	( Use of salivary levels to predict clearance of caffeine in patients with cystic fibrosis. Bianchetti, MG; Jost, J; Kraemer, R; Passweg, J; Preisig, R, )	0.59
" Compared with controls (n = 15), a significantly slowed caffeine absorption was found in gastric stasis (n = 8) by means of a lower absorption rate constant KA (0."	( Effect of altered gastric emptying on caffeine absorption. Brachtel, D; Richter, E, 1988)	0.79
"The effects of caffeine on the pharmacokinetics and bioavailability of aspirin were studied in 12 healthy adult male volunteers."	( Influence of caffeine on aspirin pharmacokinetics. Sriwatanakul, K; Thithapandha, A; Yoovathaworn, KC, )	0.85
"The absorption rate and the bioavailability of two commercially available paracetamol tablets were investigated in a panel of seven volunteers; one of these tablets contained a combination of 50 mg caffeine and paracetamol."	( Bioavailability of paracetamol after oral administration to healthy volunteers. Influence of caffeine on rate and extent of absorption. Gusdorf, CF; Sitsen, JM; Tukker, JJ, 1986)	0.68
" Bioavailability is of the order of 5% or less by oral or rectal administration."	( Clinical pharmacokinetics of ergotamine in migraine and cluster headache. Perrin, VL, )	0.13
"The 3 acetylsalicylic acid preparations showed at normal patients at the same elimination phase no significant differences concerning the bioavailability (comparison of the area under the concentration-time-curve)."	( [Comparison of the pharmacokinetic behavior of Turivital, Acesal and Micristin]. Berlet, G; Chemnitius, KH; Schröber, R; Traeger, A; Zaumseil, J, 1984)	0.27
" Application of this method during human bioavailability studies is described."	( Rapid quantitative liquid chromatographic determination of caffeine levels in plasma after oral dosing. O'Connell, SE; Zurzola, FJ, 1984)	0.51
" Finally, the absolute bioavailability was calculated."	( [Biologic availability of caffeine in subjects with regard to the variability of the elimination half life]. Banditt, P; Meyer, FP; Uchtländer, M; Walther, H; Walther, T, 1983)	0.57
" No differences were found in the quinidine absorption and disposition constants between the control and caffeine-treated phases, using a nonlinear, least-squares regression analysis of the serum quinidine concentration-time curves and standard blood and urine bioavailability test methods."	( Effect of caffeine on the oral absorption and disposition of quinidine. Meyers, DG; Ueda, CT; Wulf, BG; Zeller, FP, )	0.75
" After oral administration, caffeine was absorbed poorly with an apparent bioavailability of 39%."	( Pharmacology, pharmacokinetics, and behavioral effects of caffeine in horses. Greene, EW; Tobin, T; Woods, WE, 1983)	0.8
"The absolute bioavailability of orally administered caffeine was investigated in 10 healthy adult male volunteers, aged 18."	( The absolute bioavailability of caffeine in man. Blanchard, J; Sawers, SJ, 1983)	0.8
" 4 The oral bioavailability of caffeine was found to be complete in the one subject studied."	( Decreased systemic clearance of caffeine due to cimetidine. Broughton, LJ; Rogers, HJ, 1981)	0.83
"A rapid simple and robust reversed-phase HPLC method was developed for rapid screening in bioavailability studies or comparative bioequivalence studies."	( Rapid high-performance liquid chromatographic determination of vancomycin in human plasma. Luksa, J; Marusic, A, 1995)	0.29
"The bioavailability of the four metabolites of metamizole (CAS 68-89-3), 4-methyl-amino-antipyrine (4-MAA), 4-formyl-amino-antipyrine (4-FAA), 4-amino-antipyrine (4-AA) and 4-acetyl-amino-antipyrine (4-AcAA) was compared after oral administration of a test (Analgin) and a reference formulation, both containing 1 g of metamizole."	( Comparative bioavailability of two oral metamizole formulations. Influence of the acetylation phenotype. Bacracheva, N; Drenska, A; Gorantcheva, J; Tyutyulkova, N; Vlahov, V, 1995)	0.29
"30 hours, and bioavailability of 99."	( Application of an enzyme-multiplied immunoassay technique for determination of caffeine elimination kinetics as a test of liver function in clinically normal dogs. DeGraves, FJ; Golden, DL; Spano, JS; Whatley, EM; Wilson, RC, 1994)	0.52
" The results indicated that decaffeinated coffee and caffeine had no effect on F metabolism, whereas caffeinated coffee appeared to increase the initial absorption rate but not the 4-hour bio-availability."	( Lack of significant effect of coffee and caffeine on fluoride metabolism in rats. Chen, X; Whitford, GM, 1994)	0.8
" The reduction in bioavailability of fluoroquinolones by concurrent administration of aluminium hydroxide is more striking for derivatives with fewer substituents on the essential structure and on the piperazinyl group, such as norfloxacin, ciprofloxacin and enoxacin."	( Pharmacokinetic interactions related to the chemical structures of fluoroquinolones. Fujiwara, I; Mizuki, Y; Yamaguchi, T, 1996)	0.29
" Also, the plasma t 1/2 (of carbamazepine was prolonged by two folds and bioavailability reduced by about 32% in presence of caffeine."	( Influence of caffeine on pharmacokinetic profile of sodium valproate and carbamazepine in normal human volunteers. David, J; Joseph, T; Kulkarni, C; Vaz, J, 1998)	0.88
" In conclusion, cisapride has a positive influence on GOR parameters during caffeine treatment without impairing the oral bioavailability or therapeutic effect of caffeine."	( Effect of cisapride on acid gastro-oesophageal reflux during treatment with caffeine. Baisch, HJ; Heimann, G; Kentrup, H; Kusenbach, G; Skopnik, H, 2000)	0.77
"The quantitative structure-bioavailability relationship of 232 structurally diverse drugs was studied to evaluate the feasibility of constructing a predictive model for the human oral bioavailability of prospective new medicinal agents."	( QSAR model for drug human oral bioavailability. Topliss, JG; Yoshida, F, 2000)	0.31
" An analysis of the published literature showed that the absorption, bioavailability and route of excretion were generally similar between humans and the test species, for each probe substrate."	( Uncertainty factors for chemical risk assessment: interspecies differences in the in vivo pharmacokinetics and metabolism of human CYP1A2 substrates. Dorne, JL; Renwick, AG; Walton, K, 2001)	0.31
"The purpose of this study was to evaluate the rate of absorption and relative bioavailability of caffeine from a Stay Alert chewing gum and capsule formulation."	( The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers. Balkin, TJ; Belenky, GL; Cox, DS; Eddington, ND; Kamimori, GH; Karyekar, CS; Otterstetter, R, 2002)	0.78
" Relative bioavailability of the gum formulation after the 50, 100 and 200 mg dose was 64, 74 and 77%, respectively."	( The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers. Balkin, TJ; Belenky, GL; Cox, DS; Eddington, ND; Kamimori, GH; Karyekar, CS; Otterstetter, R, 2002)	0.56
"The use of human skin models for performing cutaneous bioavailability studies has been little investigated."	( Comparison of cutaneous bioavailability of cosmetic preparations containing caffeine or alpha-tocopherol applied on human skin models or human skin ex vivo at finite doses. Andrian, M; Benech-Kieffer, F; Dreher, F; Fouchard, F; Patouillet, C; Simonnet, JT, 2002)	0.54
" It is becoming increasingly evident, however, that the bioavailability of these compounds is poor as a result of limited absorption and presystemic metabolism by mammalian and microbial enzymes."	( Antimutagenic activity of tea: role of polyphenols. Ioannides, C; Yoxall, V, 2003)	0.32
"The results of this study revealed a pronounced effect of caffeine on the bioavailability of orally given melatonin, most probably due to inhibition of CYP1A2 activity."	( Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. Bertilsson, L; Härtter, S; Laine, K; Nordmark, A; Rose, DM; Tybring, G, 2003)	0.95
" These results appear to be correlated with in vivo data on the effects of orally administered B[a]P, that is, low (10%) bioavailability in the rats and almost no acute lethal toxicity in rats or mice."	( Feasibility of a simple double-layered coculture system incorporating metabolic processes of the intestine and liver tissue: application to the analysis of benzo[a]pyrene toxicity. Choi, S; Nishikawa, M; Sakai, Y; Sakoda, A, 2004)	0.32
" For caffeine the maximum absorption rate and the total penetration through rat skin were clearly higher than the mean value for human skin."	( In vitro predictions of skin absorption of caffeine, testosterone, and benzoic acid: a multi-centre comparison study. Cage, S; Carmichael, PL; Dick, I; Kenyon, S; Korinth, G; Larese, F; Limasset, JC; Maas, WJ; Montomoli, L; Nielsen, JB; Payan, JP; Robinson, E; Sartorelli, P; Schaller, KH; van Burgsteden, JA; van de Sandt, JJ; Wilkinson, SC; Williams, FM, 2004)	1.1
" In terms of the bioavailability of caffeine, the most important factor seemed to be the residence time in the ascending and transverse colon."	( Neutron activation-based gamma scintigraphy in pharmacoscintigraphic evaluation of an Egalet constant-release drug delivery system. Ariniemi, K; Hietanen, H; Kanerva, H; Kekki, T; Lindevall, K; Lipponen, M; Marvola, J; Marvola, M; Mykkänen, S; Slot, L, 2004)	0.6
" The bioavailability was approximately 60%."	( Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine. Beijnen, JH; de Jonge, ME; den Hoed, R; Hendriks, VM; Huitema, AD; Sparidans, RW; van den Brink, W; van Ree, JM; Zandvliet, AS, 2005)	0.61
" The relative bioavailability of ephedrine differed between the herbal supplement compared with the pharmaceutical formulation."	( Mechanistic pharmacokinetic modelling of ephedrine, norephedrine and caffeine in healthy subjects. Benowitz, NL; Csajka, C; Haller, CA; Verotta, D, 2005)	0.56
" Among the different activities of EGCG observed in cell culture systems, we need to select the physiologically relevant ones based on the biological importance of the target as well as the effective concentration and whether the reaction can take place in vivo because of the limited bioavailability of EGCG."	( Possible mechanisms of the cancer-preventive activities of green tea. Hou, Z; Ju, J; Lambert, JD; Lu, G; Sang, S; Yang, CS, 2006)	0.33
" Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects."	( Hologram QSAR model for the prediction of human oral bioavailability. Andricopulo, AD; Moda, TL; Montanari, CA, 2007)	0.34
" The model was more successful at simulating double-peak phenomena in absorption rate profiles and onset of caffeine absorption."	( Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans. Amidon, GL; Choe, SY; Higaki, K; Löbenberg, R; Welage, LS, 2008)	0.56
"Stratum corneum composition and structure limit cutaneous bioavailability of pharmaceutical and cosmetical agents."	( In vitro evaluation of the effect of electrotreatment on skin permeability. Kalia, YN; Levy, JL; Marra, F; Santi, P, 2008)	0.35
" Induction of Cytochrome P450 (Cyp)1b1 in maternal liver may reduce bioavailability of DBP to the fetus as a mechanism of chemoprevention."	( Chemoprevention of dibenzo[a,l]pyrene transplacental carcinogenesis in mice born to mothers administered green tea: primary role of caffeine. Castro, DJ; Dashwood, RH; Fischer, KA; Giovanini, JN; Löhr, CV; Orner, GA; Pereira, CB; Williams, DE; Yu, Z, 2008)	0.55
" However, data on the bioavailability of CGA from green coffee in humans are inexistent."	( Chlorogenic acids from green coffee extract are highly bioavailable in humans. Donangelo, CM; Farah, A; Lafay, S; Monteiro, M, 2008)	0.35
" Interoccasion variability was smaller compared to interindividual variability in clearance, volume and absorption rate (27% vs."	( Population pharmacokinetics of caffeine in healthy male adults using mixed-effects models. Fan, W; Fun, CY; Law, YL; Lim, CL; Lim, WM; Seng, KY, 2009)	0.64
" These findings (modulation of plasma EGCG level by CAF) provide ideas for modulating the bioavailability of tea catechins, which can be applied to tea-related drinks and foods."	( Effects of co-administration of tea epigallocatechin-3-gallate (EGCG) and caffeine on absorption and metabolism of EGCG in humans. Kimura, F; Miyazawa, T; Nakagawa, K; Nakamura, M; Nakayama, K; Niino, H; Sookwong, P; Tsuduki, T, 2009)	0.58
" It is proposed that by modifying the cellular redox state, caffeine ultimately reduces the pool of reactive oxygen species, thereby increasing the bioavailability of endogenous melatonin for interaction with zolpidem."	( The paradox of caffeine-zolpidem interaction: a network analysis. Myslobodsky, M, 2009)	0.95
"High solubility and high permeability of caffeine rank it among class I of BCS and well absorbed compounds."	( Caco-2 cells and Biopharmaceutics Classification System (BCS) for prediction of transepithelial transport of xenobiotics (model drug: caffeine). Kholova, D; Kvetina, J; Smetana, J; Smetanova, L; Stetinova, V; Svoboda, Z, 2009)	0.82
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."	( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination. Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010)	0.36
" Adding energy drinks to alcohol tends to increase the rate of absorption through its carbonation and dilution of the alcohol, and keep a person awake longer allowing ingestion of a greater volume of alcohol."	( Risks of alcoholic energy drinks for youth. Weldy, DL, )	0.13
" To show the importance of physicochemical properties, the classic QSAR and CoMFA of neonicotinoids and prediction of bioavailability of pesticides in terms of membrane permeability in comparison with drugs are described."	( Importance of physicochemical properties for the design of new pesticides. Akamatsu, M, 2011)	0.37
" Pharmacokinetic parameters describing absorption rate and extent of absorption through hair follicles or the stratum corneum were determined separately and compared with each other."	( Hair follicles contribute significantly to penetration through human skin only at times soon after application as a solvent deposited solid in man. Grice, JE; Lademann, J; Liu, X; Otberg, N; Patzelt, A; Roberts, MS; Trauer, S, 2011)	0.37
" The absorption rate constant of caffeine for hair follicles was nearly 10 times higher than that for the stratum corneum and the percentage of absorption from hair follicles was more than half of that of the stratum corneum."	( Hair follicles contribute significantly to penetration through human skin only at times soon after application as a solvent deposited solid in man. Grice, JE; Lademann, J; Liu, X; Otberg, N; Patzelt, A; Roberts, MS; Trauer, S, 2011)	0.65
" The cocrystals outperformed QUE dihydrate with increases in bioavailability up to nearly 10-fold."	( Cocrystals of quercetin with improved solubility and oral bioavailability. Kavuru, P; Shytle, RD; Smith, AJ; Wojtas, L; Zaworotko, MJ, 2011)	0.37
" Anagrelide is metabolized by cytochrome P450 (CYP) 1A2, and previous studies of the effect of food on the bioavailability and pharmacokinetics of anagrelide were conducted prior to the identification of the active metabolite, 3-hydroxyanagrelide."	( Cardiovascular safety of anagrelide in healthy subjects: effects of caffeine and food intake on pharmacokinetics and adverse reactions. Datino, T; Fernández-Avilés, F; Figueiras-Graillet, L; Franklin, R; Gama, JG; Jones, C; Martínez-Sellés, M, 2013)	0.63
" However, maximum plasma concentration, half-life, area under the curve, and oral bioavailability were not different."	( Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients. Chalasani, N; Hall, SD; Jones, DR; Mattar, S; Tandra, S; Vuppalanchi, R, 2013)	0.39
" Finally, we demonstrated that the biological activity of Trp-P-1 and Trp-P-2 is strictly dependent on the presence of the mutagen in a free (unbound with methylxanthine) form, suggesting that mutagen sequestration in stacking heterocomplexes with methylxanthines can decrease its bioavailability and diminish its biological effects."	( Caffeine and other methylxanthines as interceptors of food-borne aromatic mutagens: inhibition of Trp-P-1 and Trp-P-2 mutagenic activity. Gołuński, G; Kaźmierkiewicz, R; Piosik, J; Woziwodzka, A; Wyrzykowski, D, 2013)	1.83
" The bioavailability and the distribution of each compound and its metabolites also contribute to coffee mechanisms of action."	( Coffee components and cardiovascular risk: beneficial and detrimental effects. Buscemi, S; Galvano, F; Godos, J; Grosso, G; Li Volti, G; Marventano, S; Pluchinotta, FR, 2014)	0.4
" In medicine, cocrystals are obtained by crystallization of active pharmaceutical ingredients with precisely chosen coformers to design medicaments that demonstrate enhanced stability, high solubility, and therefore high bioavailability and optimized drug up-take."	( Continuous engineering of nano-cocrystals for medical and energetic applications. Klaumünzer, M; Pichot, V; Risse, B; Schaefer, MR; Schnell, F; Spitzer, D, 2014)	0.4
" In this study we have assessed the cutaneous bioavailability of caffeine as hydrophilic compound model using Franz diffusion cell and VitroPharma."	( New easy handling and sampling device for bioavailability screening of topical formulations. Gilbert, E; Gioia, B; Haftek, M; Pirot, F; Pivot, C; Salmon, D; Verrier, B, 2015)	0.65
" Bioavailability of midazolam was 4% in marmosets, presumably because of contribution of marmoset P450 3A4 expressed in small intestine and liver, with a high catalytic efficiency for midazolam 1'-hydroxylation as evident in the recombinant system."	( Simultaneous pharmacokinetics evaluation of human cytochrome P450 probes, caffeine, warfarin, omeprazole, metoprolol and midazolam, in common marmosets (Callithrix jacchus). Inoue, T; Sasaki, E; Shimizu, M; Toda, A; Uehara, S; Uno, Y; Utoh, M; Yamazaki, H, 2016)	0.67
" Lateral diffusivity is expected to be an important determinant of the topical bioavailability of ZnPT, which is characteristically administered as a fine suspension and must reach microorganisms in molecular form to exert biocidal activity."	( A quantitative radioluminographic imaging method for evaluating lateral diffusion rates in skin. Kasting, GB; Miller, MA; Rush, AK; Smith, ED, 2015)	0.42
" The bioavailability of orally applied caffeine was also significantly decreased (p = 0."	( Pharmacokinetic Herb-Drug Interaction between Essential Oil of Aniseed (Pimpinella anisum L., Apiaceae) and Acetaminophen and Caffeine: A Potential Risk for Clinical Practice. Božin, B; Mijatović, V; Petković, S; Samojlik, I; Stilinović, N; Vukmirović, S, 2016)	0.91
" In vivo pharmacokinetic testing revealed that inverse agonist 8c is orally bioavailable and has vastly reduced brain penetration compared to rimonabant."	( Pyrazole antagonists of the CB1 receptor with reduced brain penetration. Amato, G; Bortoff, K; Fulp, A; Maitra, R; Seltzman, H; Snyder, R; Wiethe, R; Zhang, Y, 2016)	0.43
"The Cosmetics Europe Skin Bioavailability and Metabolism Task Force aims to improve the measurement and prediction of the bioavailability of topically-exposed compounds for risk assessment."	( Comparison of protocols for measuring cosmetic ingredient distribution in human and pig skin. Cubberley, R; Duplan, H; Eilstein, J; Gerstel, D; Grégoire, S; Hewitt, N; Jacques-Jamin, C; Klaric, M; Rothe, H; Schepky, A, 2016)	0.43
" The results indicate a way to control the size of cocrystals on a nanometer scale, which will provide higher bioavailability of pharmaceuticals."	( Raman Spectroscopy of Pharmaceutical Cocrystals in Nanosized Pores of Mesoporous Silica. Ajito, K; Ohta, R; Ueno, Y, 2017)	0.46
" These non-specific membrane interactions may increase the efficacy of analgesic drugs through changes in the bioavailability and rate of metabolism of these drugs."	( Partitioning of caffeine in lipid bilayers reduces membrane fluidity and increases membrane thickness. Alsop, RJ; Backholm, M; Dhaliwal, A; Khondker, A; Rheinstädter, MC; Shi, AC; Tang, J, 2017)	0.8
"Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance."	( Effect of Short-Term Fasting on Systemic Cytochrome P450-Mediated Drug Metabolism in Healthy Subjects: A Randomized, Controlled, Crossover Study Using a Cocktail Approach. Achterbergh, R; Lammers, LA; Mathôt, RAA; Romijn, JA; van Schaik, RHN, 2017)	0.46
"Liposomes are commonly used in cosmetic formulations to increase the bioavailability of active ingredients."	( Skin delivery of hydrophilic molecules from liposomes and polysaccharide-coated liposomes. Arab-Tehrany, E; Belhaj, N; Bézivin, C; Loing, E, 2017)	0.46
"Results showed that both coated and non-coated liposomes significantly improved the bioavailability of hydrophilic active molecules in skin, compared to reference solutions."	( Skin delivery of hydrophilic molecules from liposomes and polysaccharide-coated liposomes. Arab-Tehrany, E; Belhaj, N; Bézivin, C; Loing, E, 2017)	0.46
" The bioavailability of the filters was extremely low regardless of the extent of skin damage, suggesting bioavailability would not be increased if the consumer applied the sunscreen to sun-damaged skin."	( Standardization of an in vitro Model for Evaluating the Bioavailability of Topically Applied Compounds on Damaged Skin: Application to Sunscreen Analysis. Bessou-Touya, S; Domergue, A; Duplan, H; Jacques-Jamin, C; Jeanjean-Miquel, C, 2017)	0.46
" The two studied bariatric surgical techniques normalize paracetamol oral bioavailability without impairing the liver function (measured by cytochrome P450 1A2 activity)."	( Pharmacokinetics in Morbid Obesity: Influence of Two Bariatric Surgery Techniques on Paracetamol and Caffeine Metabolism. Boix, DB; Civit, E; de la Torre, R; Farré, M; Goday Arno, A; Grande, L; Langohr, K; Le Roux, JAF; Lí Carbó, M; Nino, OC; Papaseit, E; Pera, M; Pérez-Mañá, C; Ramon, JM; Rodríguez-Morató, J, 2017)	0.67
" Compound 12g with MIC values of 5 μg/ml as a representative may possess better oral bioavailability and indicated high permeability by the parallel artificial membrane permeation assay of the blood-brain barrier (PAMPA-BBB)."	( Discovery of novel anti-tuberculosis agents with pyrrolo[1,2-a]quinoxaline-based scaffold. An, Q; Deng, Y; Liu, P; Luo, Y; Sang, Z; Tang, Y; Wang, T; Yang, T; Yang, Y; Zhang, T, 2018)	0.48
" The conjugation of alginate beads within an orodispersible film matrix represents an effective oral/buccal delivery system that induces a controlled release along with an enhanced intimate contact with cell layers that may promote higher in vivo bioavailability of carried drugs."	( Incorporation of beads into oral films for buccal and oral delivery of bioactive molecules. Castro, PM; Madureira, AR; Magalhães, R; Pilosof, AMR; Pintado, ME; Ruiz-Henestrosa, VMP; Sarmento, B; Sousa, F, 2018)	0.48
" The alkaloids caffeine and trigonelline, as well as the polyphenol chlorogenic acid, are some of the most important bioactive organic compounds of these beverages, displaying high levels in both espresso and common brews and/or increased bioavailability after consumption."	( Drinking for protection? Epidemiological and experimental evidence on the beneficial effects of coffee or major coffee compounds against gastrointestinal and liver carcinogenesis. Barbisan, LF; Chaves, MAG; Cogliati, B; Moreno, FS; Rocha, AB; Romualdo, GR; Vinken, M, 2019)	0.87
"An understanding of the bioavailability of topically applied cosmetics ingredients is key to predicting their local skin and systemic toxicity and making a safety assessment."	( Comparison of the metabolism of 10 cosmetics-relevant chemicals in EpiSkin™ S9 subcellular fractions and in vitro human skin explants. Arbey, E; Cubberley, R; Duplan, H; Eilstein, J; Ellison, C; Fabre, A; Géniès, C; Grégoire, S; Hewitt, NJ; Jacques-Jamin, C; Klaric, M; Lange, D; Rothe, H; Schepky, A, 2020)	0.56
" Hence, using nanotechnology is a viable alternative to primarily improve the physicochemical characteristics and bioavailability of guarana."	( Protective effect of guarana-loaded liposomes on hemolytic activity. da Cruz, IBM; Dalcin, AJF; Gomes, P; Mitjans, M; Ourique, AF; Ribeiro, EE; Roggia, I; Vinardell, MP, 2020)	0.56
" It is currently unknown whether these protective effects are related to caffeine (CAF), or to its combination with other common and/or highly bioavailable coffee compounds, such as trigonelline (TRI) and chlorogenic acid (CGA)."	( The combination of coffee compounds attenuates early fibrosis-associated hepatocarcinogenesis in mice: involvement of miRNA profile modulation. Barbisan, LF; Cogliati, B; da Silva, TC; Evangelista, AF; Moreno, FS; Prata, GB; Reis, RM; Romualdo, GR; Vinken, M, 2020)	0.79
" Apparent oral clearance and relative bioavailability for caffeine and S-warfarin were not significantly different between the subject populations."	( Therapeutic Protein Drug Interaction Potential in Subjects With Psoriasis: An Assessment Based on Population Pharmacokinetic Analyses of Sensitive Cytochrome P450 Probe Substrates. Mohamed, MF; Othman, AA; Sathe, AG, 2021)	0.87
" Caffeine is rapidly absorbed with complete bioavailability following oral dosing."	( Pharmacokinetics, pharmacodynamics and metabolism of caffeine in newborns. Aranda, JV; Beharry, KD, 2020)	1.72
"Agglomeration of active pharmaceutical ingredients (API) in tablets can lead to decreased bioavailability in some enabling formulations."	( Diagnosis of Agglomeration and Crystallinity of Active Pharmaceutical Ingredients in Over the Counter Headache Medication by Electrospray Laser Desorption Ionization Mass Spectrometry Imaging. Dimmitt, NH; Green, AM; Hubbard, ND; Khan, SM; McVey, PA; Taulbee-Cotton, BV; Van Meter, MI; Webster, GK, 2021)	0.62
" The results showed that caffeine and ferulic acid, as well as green Robusta coffee, demonstrated the greatest inhibition of MAO-A activity, which may increase the bioavailability of serotonin."	( Evaluation of the inhibition of monoamine oxidase A by bioactive coffee compounds protecting serotonin degradation. Budryn, G; Gałązka-Czarnecka, I; Grzelczyk, J; Oracz, J; Peña-García, J; Pérez-Sánchez, H; Szwajgier, D, 2021)	0.92
"Co-administration of PIO with caffeine enhances its antidiabetic effect, probably due to enhanced bioavailability of PIO, leading to clinical benefits in diabetic patients."	( Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats: Impact on therapeutics. Alkahtani, SA; Alshabi, AM; Habeeb, MS; Shaikh, IA, 2021)	2.35
" Unexpected interactions may lead to changes in bioaccessibility, bioactivity, and bioavailability of phytochemicals."	( Identify the interactions between phytochemicals and proteins in the complicated food matrix. Liu, PF; Mengesha, NM; Tsai, YH, 2021)	0.62
" Encapsulation of substances into nanoparticles was expected to be promising to increase the bioavailability of topically applied products."	( Influence of nanocrystal size on the in vivo absorption kinetics of caffeine after topical application. Breuckmann, P; Jaenicke, T; Keck, CM; Klein, AL; Krutmann, J; Lademann, J; Meinke, MC; Müller, RH; Patzelt, A; Rasulev, U, 2021)	0.86
" A reliable assessment of skin penetration enhancing properties, mechanism of action of carrier systems, and an estimation of a bioavailability are essential for transdermal delivery."	( Comparison Between Franz Diffusion Cell and a novel Micro-physiological System for In Vitro Penetration Assay Using Different Skin Models. Aiello, M; Fedi, A; Lubda, M; Marzagalli, M; Pulsoni, I; Scaglione, S; von Hagen, J, 2022)	0.72
"Based on the presented results it can be assumed that high caffeine consumption may lead to suppression of iron bioavailability through increased inflammation."	( Caffeine and alcohol - Friends or foes of human iron stores? Dziembowska, I; Wójcik, M; Żekanowska, E, 2022)	2.41
" Due to its high barrier function and different diffusion characteristics, skin governs the efficacy of these active ingredients and a bioavailability in the epidermal and dermal tissue."	( Lateral Dermal Penetration Is Dependent on the Lipophilicity of Active Ingredients. Kolmar, H; Lubda, M; Salazar, A; von Hagen, J; Zander, M, 2022)	0.72
" Recent studies showed that flavan-3-ols could interact with methylxanthines, evidenced by an increase in flavan-3-ol bioavailability with a concomitant increase in flavan-3-ol intake-mediated vascular effects."	( Flavan-3-ol-methylxanthine interactions: Modulation of flavan-3-ol bioavailability in volunteers with a functional colon and an ileostomy. Borges, G; Crozier, A; Dobani, S; Durkan, R; Ensunsa, JL; Fong, RY; Gill, CIR; Kane, E; Kimball, J; Lawther, R; Medici, V; O'Connor, G; Ottaviani, JI; Pourshahidi, LK; Schroeter, H; Ward, K, 2023)	0.91
" The buccal mucosa has been extensively studied as an alternative route for drug delivery as it improves the bioavailability of drugs administered via the peroral route."	( Candesartan exhibits low intrinsic permeation capacity and affects buccal tissue viability and integrity: An ex vivo study in porcine buccal mucosa. Garcia-Tarazona, YM; Gordillo, JFI; Lafaurie, GI; Morantes, SJ; Ramos, FA; Sepúlveda, P, 2023)	0.91

Dosage Studied

Caffeine exerts mild deleterious dose-response effects on recovery sleep following total sleep deprivation. The potential recovery from these effects after sufficient sleep as suggested by lack of post-recovery sleep performance deficits.

Excerpt	Relevance	Reference
"In 6-day pregnant New Zealand White rabbits dosed intravenously with 3H-nicotine, the 3H-activity in the uterine fluid was approximately 5 to 11 times greater than that in the plasma at the corresponding times; 3H-nicotine itself accounted for most of this radioactivity."	( Accumulation of nicotine in the uterine fluid of the six-day pregnant rabbit. Dames, NM; Fabro, S; McLachlan, JA; Sieber, SM, 1976)	0.26
" Hence it might not be always necessary to take into consideration changes in the surface area as a function of dissolution rate, and the 1n W infinity/(W infinity) versus time plot devised by Kitazawa & others might be a useful and simple means of obtaining the dissolution rate constant of an active ingredient from a dosage form such as compressed tablet."	( Interpretation of dissolution rate data from in vitro testing of compressed tablets. Johno, I; Kitazawa, S; Minouchi, T; Okada, J, 1977)	0.26
" This timed release dosage form has been prepared by means of a fluidized bed coating technique using ethyl cellulose as the polymeric film and caffeine and salicylic acid as model drugs."	( Placebo granules as cores for timed release drug delivery systems. Donbrow, M; Friedman, M; Samuelov, Y, 1979)	0.46
" Caffeine caused a shift in the dose-response curve for hexobarbital but no changes in hexobarbital distribution and elimination."	( Hexobarbital blood levels and effects on EEG in the presence and absence of caffeine. Atkinson, J; Milon, H, 1979)	1.4
" With a wild-type strain a whole dose-response curve was obtained."	( Caffeine toxicity in drosophila strains having different MMS sensitivities. Graf, U; Nigsch, J; Würgler, FE, 1977)	1.7
" Previous reports that caffeine enhances induced mutation frequencies are explained by an artefact in the situ method used; a similar artefact may also explain the cumulative in situ mutation dose-response curves."	( Failure of caffeine to influence induced mutation frequencies and the independence of cell killing and mutation induction in V79 Chinese hamster cells. Fox, M; McMillan, S, 1979)	0.96
" These observations have led to clear conclusions on the optimum timing and dosage of theophylline, and on the need to monitor plasma levels of both theophylline and caffeine in newborn infants treated with theophylline."	( Plasma xanthine levels in low birthweight infants treated or not treated with theophylline. Brazier, JL; Renaud, H; Ribon, B; Salle, BL, 1979)	0.45
" Examination of the complete dose-response curve provided the best comparative information and caffeine was the consistent predictor of susceptibility."	( Muscle contractures and adenosine triphosphate depletion in porcine malignant hyperthermia. Gronert, GA, )	0.35
" The dosage of analgesic compound required to control each episode of tension headache was smaller than that of acetaminophen."	( Study of a new analgesic compound in the treatment of tension headache. Borges, J; Zavaleta, C, 1976)	0.26
" The records obtained of the effect of the dosage can be seen as a measure of the efficiency of this method."	( [The influence of centrally acting drugs on flicker fusion frequency]. Feller, K; Graupner, K; Kálmán, E; von Littrow, C, 1975)	0.25
" However, no dose-response relationship was demonstrated between LUT cancer and usual daily coffee consumption or "cup-years" of coffee drinking."	( Coffee drinking and cancer of the lower urinary tract. Cole, P; Simon, D; Yen, S, 1975)	0.25
"An automated high-pressure liquid chromatographic (HPLC) method for the separation and determination of aspirin, phenacetin, and caffeine in pharmaceutical dosage forms is descreibed."	( Automated high-pressure liquid chromatographic analysis of aspirin, phenacetin, and caffeine. Ascione, PP; Chrekian, GP, 1975)	0.68
"The dose-response relationships for three stimulants have been explored."	( The effects of age and illumination on the dose-response curves for three stimulants. Isaac, W; Kallman, WM, 1975)	0.25
" In addition, the effect on the norepinephrine dose-response curve of the combination of a methyixanthine and U-0521,the latter a potent inhibitor of catechol O-methyltransferase, the major enzyme of catecholamine inactivation in vascular tissue, did not differ from that of U-0521 alone."	( Mechanism of methylxanthine sensitization of norepinephrine responses in a coronaryartery. Frew, RD; Kalsner, S; Smith, GM, 1975)	0.25
" We compared the dose-response relations of caffeine, regular coffee and decaffeinated coffee for gastric acid secretion and sphincter pressure in normal subjects."	( Gastric acid secretion and lower-esophageal-sphincter pressure in response to coffee and caffeine. Booth, GH; Cohen, S, 1975)	0.74
" Groups of homozygotes were dosed by gavage with aspirin, phenacetin and paracetamol for 4 weeks."	( The induction of renal papillary necrosis in Gunn rats by analgesics and analgesic mixtures. Axelsen, RA, 1975)	0.25
" At appropriate doses the CDP effect is reversed by repeated testing, by pretreatment with CDP, and by concomitant dosing with caffeine."	( The mechanism of anti-muricidal effects of chlordiazepoxide. Feldman, RS; Quenzer, LF, )	0.34
" As a first step, a dose-response curve was obtained (concentrations of 5-50 micrograms/ml)."	( Schedule dependent variation in human lymphocyte sensitivity to bleomycin and repair of chromosomal aberrations in G2. Koldamova, RP; Lefterov, IM, 1992)	0.28
" This may partly be explained by intertrial differences in dosage and study design."	( Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine. Fuhr, U; Granneman, GR; Kinzig, M; Mahr, G; Muth, P; Nickel, P; Patterson, K; Sörgel, F; Stephan, U, 1992)	0.52
" Thereafter, a dose-response curve for caffeine (2."	( Undernutrition during suckling has no effect on the rat locomotor activity response to caffeine. Dias, RD; Huang, CI; Mello, CF; Rocha, JB, 1992)	0.78
" The effect exhibited a significant dose-response relationship, with the number of cups of coffee consumed per day being inversely related to asthma prevalence."	( Caffeine intake and asthma symptoms. Schwartz, J; Weiss, ST, 1992)	1.73
" The methylxanthine induces dose-response increases in locomotor activity in animals."	( Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Daval, JL; Debry, G; Nehlig, A, )	1.57
" However, in rats trained on caffeine, PPA had no effect on the dose-response relationship for caffeine; similarly, in rats trained on PPA, caffeine had no effect on the dose-response relationship for PPA (no synergism or antagonism)."	( Drug discrimination studies in rats with caffeine and phenylpropanolamine administered separately and as mixtures. Mariathasan, EA; Stolerman, IP, 1992)	0.84
" These findings suggest that CA pharmacokinetic parameters can be estimated using a simplified three-point blood sampling procedure following a single oral load and that the serum PX/CA or (PX + TB + TP)/CA ratio in a single blood sample taken 2 or 4 h after dosing provides a useful indicator for the assessment of hepatic drug-oxidizing capacity, N-demethylation, in decompensated liver cirrhosis."	( A simple useful method for the determination of hepatic function in patients with liver cirrhosis using caffeine and its three major dimethylmetabolites. Fukao, K; Ishikawa, A; Iwasaki, Y; Misawa, S; Osada, A; Tanaka, E; Tsuji, K; Yamamoto, Y, 1992)	0.5
" Discriminant Function Analysis revealed a dose-response association between prenatal cigarette exposure and impulsive behavior as manifest on poorer performance on a response inhibition task and increased errors of commission on a sustained vigilance task."	( A follow-up study of attentional behavior in 6-year-old children exposed prenatally to marihuana, cigarettes, and alcohol. Fried, PA; Gray, R; Watkinson, B, )	0.13
"Six blood samples covering a 24 hr post caffeine dosage were drawn in 8 healthy subjects and 18 patients with liver cirrhosis."	( The theophylline disposition after caffeine administration in liver cirrhosis: an index of liver function. Becker, A; Hartleb, M; Mańczyk, I; Romańczyk, T; Spalińska, M; Waluga, M; Zieliński, M, )	0.68
" This trial design (crossover with multiple dosing in outpatients) is a sensitive way of testing for analgesia, and is potentially more predictive of adverse effect problems than single-dose studies."	( A multiple dose comparison of combinations of ibuprofen and codeine and paracetamol, codeine and caffeine after third molar surgery. Carroll, D; Guest, P; Juniper, RP; McQuay, HJ; Moore, RA, 1992)	0.5
" The metabolism of theophylline and caffeine is inhibited by enoxacin and ciprofloxacin such that the dosage of theophylline may need to be reduced in order to avoid toxicity."	( Interactions of fluoroquinolones with other drugs: mechanisms, variability, clinical significance, and management. Dudley, MN; Marchbanks, CR; Radandt, JM, 1992)	0.56
" Acute caffeine dosage did not alter ex vivo adenosine receptor binding affinity or density in any brain regions."	( Caffeine-induced behavioral stimulation is dose-dependent and associated with A1 adenosine receptor occupancy. Arcelin, G; Cotreau, MM; Greenblatt, DJ; Kaplan, GB; Kent, MA; Shader, RI, 1992)	2.18
" The dose-response curve was bell-shaped for both compounds."	( Production of protein-associated DNA breaks by 8-methoxycaffeine, caffeine and 8-chlorocaffeine in isolated nuclei from L1210 cells: comparison with those produced by topoisomerase II inhibitors. Kohn, KW; Parodi, S; Pedrini, AM; Poggi, L; Pommier, Y; Russo, P, 1991)	0.53
" Millimolar concentration of ATP, which is present physiologically, will shift the dose-response relation of IP3 toward the higher IP3 concentration and enhance the maximal effect of IP3."	( Effects of adenine nucleotides on inositol 1,4,5-trisphosphate-induced calcium release in vascular smooth muscle cells. Iino, M, 1991)	0.28
" To investigate the secretory response of these substances, and to construct dose-response curves 10-day-old conscious rats were given subcutaneously a single injection of caerulein, secretin, caffeine or the combination of these compounds (caerulein + secretin, caerulein + caffeine)."	( Secretin potentiates, caffeine does not affect caerulein--stimulated pancreatic enzyme depletion and growth in newborn rats. Ammann, RW; Dobronyl, I; Papp, M; Varga, G, 1990)	0.78
" The whole-body concentrations of hexobarbital (100 mg/kg dose) in mice 30 min after dosing were 14."	( Inhibition and induction of drug metabolism by psoralens: alterations in duration of sleep induced by hexobarbital and in clearance of caffeine and hexobarbital in mice. Apseloff, G; Gerber, N; Hilliard, JB; Mays, DC, 1991)	0.48
" In the presence of [Mg2+]o, substitution of foreign anions resulted in alterations in the agonist contractile dose-response curves; EC50s were increased whereas maximum tensions were depressed."	( Interactions of magnesium and chloride ions on tone and contractility of vascular muscle. Altura, BM; Altura, BT; Carella, A; Zhang, A, 1991)	0.28
" The usual dosage is approximately 200 mg, a level of caffeine ingestion equivalent to two cups of brewed coffee."	( Failure of caffeine to affect metabolism during 60 min submaximal exercise. Ishee, JH; Riggs, CE; Titlow, LW, 1991)	0.92
" Dose-response measurements with tissues from intact or sympathectomized (6-OHDA) animals indicate that the thermogenic effects of low concentrations of ephedrine and also of caffeine are entirely dependent upon the presence of intact sympathetic nerve endings, and thus depend on presynaptic mechanisms."	( Peripheral mechanisms of thermogenesis induced by ephedrine and caffeine in brown adipose tissue. Dulloo, AG; Girardier, L; Seydoux, J, 1991)	0.71
"This study was performed to investigate the possible influence of repeated omeprazole dosing on the metabolism of caffeine, which has been shown to reflect the activity of one specific enzyme within the hepatic cytochrome P450 family, P450IA2."	( Omeprazole treatment does not affect the metabolism of caffeine. Andersson, T; Bergstrand, R; Cederberg, C; Eriksson, S; Lagerström, PO; Skånberg, I, 1991)	0.74
" Drug interactions were studied by redetermining the cocaine dose-response curve in the presence of various fixed doses of the other drugs."	( The effects of cocaine in combination with other drugs of abuse on schedule-controlled behavior in the pigeon. Evans, EB; Wenger, GR, 1990)	0.28
" However, the effects of the four agents on the clonal survival of irradiated cells failed to correlate with the extent of override, both in terms of the relative effects of the four agents and the dose-response relationships; at a concentration of 1 mM only caffeine was found to potentiate cell killing as well as causing block override, whilst at higher concentrations all the agents had a significant effect on survival but little or no further influence on the degree of block override."	( Override of the radiation-induced mitotic block in human tumour cells by methylxanthines and its relationship to the potentiation of cytotoxicity. Musk, SR; Steel, GG, 1990)	0.46
" The dose-response curve for amphetamine was shifted downward and to the right by reserpine but was flattened by AMPT."	( Depletion of catecholamines in the brain of rats differentially affects stimulation of locomotor activity by caffeine, D-amphetamine, and methylphenidate. Finn, IB; Holtzman, SG; Iuvone, PM, 1990)	0.49
" Relationships between the plasma and urine concentrations and clearances of caffeine over successive dosage intervals at steady-state were investigated in six healthy volunteers administered caffeine, 150 mg 8 hourly for 6 days."	( Caffeine renal clearance and urine caffeine concentrations during steady state dosing. Implications for monitoring caffeine intake during sports events. Birkett, DJ; Miners, JO, 1991)	1.95
" Alcohol intake was independently associated with increased risk of both hip and forearm fractures and with a dose-response relation."	( Caffeine, moderate alcohol intake, and risk of fractures of the hip and forearm in middle-aged women. Colditz, GA; Hernandez-Avila, M; Rosner, B; Speizer, FE; Stampfer, MJ; Willett, WC, 1991)	1.72
"We have recently demonstrated dose-dependency of caffeine metabolism under multiple dosing conditions."	( Effects of caffeine with repeated dosing. Benowitz, NL; Brown, CR; Denaro, CP; Jacob, P, 1991)	0.93
" A comparison between the single and the "cocktail" dosage did not reveal any significant differences in the pharmacokinetic parameters."	( [Simultaneous administration of various model substances for characterizing in vivo biotransformation in chronic liver diseases]. Henschel, L; Hoffmann, A; Huster, A; Jorke, D; Kraul, H; Reinhardt, M; Töpfer, R; Truckenbrodt, J, 1990)	0.28
" Twenty-two percent of diet aid users and 7 percent of cold medicine users reported that they deliberately used more than the dosage recommended to improve efficacy."	( Phenylpropanolamine and caffeine use among diet center clients. Lake, CR; Quirk, R; Rosenberg, D, 1990)	0.59
" Salbutamol did not influence the caffeine dose-response curves in any of the groups (n = 14 in the MH-non-susceptible (MHN) group)."	( Influence of salbutamol on the in vitro muscle response to caffeine and halothane in malignant hyperthermia. Bendixen, D; Ording, H, 1990)	0.8
" Venous blood samples were obtained before dosing and at minutes 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180."	( Effect of paraxanthine on FFA mobilization after intravenous caffeine administration in humans. Brown, DD; Hetzler, RK; Knowlton, RG; Perkins, RM; Somani, SM, 1990)	0.52
" The study supports the following conclusions: (1) caffeine reduces KAE in high impulsive subjects; (2) the larger dose of caffeine (4 mg/kg) enhances KAE in low impulsive subjects; (3) caffeine produces profound effects on the performance of high impulsives; (4) caffeine leads to different dose-response trends in the two groups."	( Caffeine differentially affects kinesthetic aftereffect in high and low impulsives. Gupta, BS; Gupta, U, 1990)	1.97
" The dose-response curve for the halothane-induced contractures of Ca2(+)-loaded skinned fibers was displaced to the left after denervation."	( Alterations in the functional properties of skinned fibers from denervated rabbit skeletal muscle. Suarez-Kurtz, G; Sudo, RT; Trachez, MM, 1990)	0.28
"The dose-response effects of administration of 8-cyclopentyltheophylline (CPT) (10, 20, and 40 mg/kg intraperitoneally [IP]) and alloxazine (ALX) (12."	( A comparison of the effects of caffeine, 8-cyclopentyltheophylline, and alloxazine on sleep in rats. Possible roles of central nervous system adenosine receptors. Pilditch, M; Radulovacki, M; Ticho, S; Virus, RM, 1990)	0.57
"Some recent epidemiologic studies have reported a nonlinear dose-response in the relationship between coffee consumption and health risks, such that the risks increase disproportionately to the increase in dose."	( Dose-dependency of caffeine metabolism with repeated dosing. Benowitz, NL; Brown, CR; Denaro, CP; Jacob, P; Wilson, M, 1990)	0.61
"We examined directly the effects of a moderate dosage of caffeine (400 mg/d) on the calcium economy in 16 healthy premenopausal women in a double-blind, placebo-controlled crossover design."	( Effects of moderate caffeine intake on the calcium economy of premenopausal women. Barger-Lux, MJ; Heaney, RP; Stegman, MR, 1990)	0.85
" The technique is simple and rapid: 4 anticonvulsants are simultaneously extracted and dosed, valproic acid, only has to be dosed lonely."	( [Plasma determination of 7 common drugs by high performance liquid chromatography]. Baty, C; Jambou, J; Leducq, B; Richard, L, 1989)	0.28
" Oxo-metabolites of enoxacin and, to a lesser extent, pefloxacin and ciprofloxacin interfere with the hepatic elimination of theophylline and caffeine and may result in toxicity due to these agents if dosage is not modified."	( Adverse reactions and interactions of fluoroquinolones. Ball, P, 1989)	0.48
" In contrast, propranolol shifted the caffeine dose-response curve to the right and significantly increased the caffeine threshold in the MHS group."	( Influence of propranolol on the in vitro response to caffeine and halothane in malignant hyperthermia-susceptible muscle. Ording, H, 1989)	0.8
" The dose-response of stimulation of Ca2+ uptake with cGMP indicated an ED50 of 5 nM cGMP."	( Cyclic guanosine monophosphate-enhanced sequestration of Ca2+ by sarcoplasmic reticulum in vascular smooth muscle. Twort, CH; van Breemen, C, 1988)	0.27
" Topographic pharmaco-EEG seems not only to confirm our previous knowledge that quantitative analysis of the human EEG in combination with certain statistical procedures ("quantitative pharmaco-EEG") is a valuable method to determine if, how, when and at which dosage a drug will be centrally effective, but also to have the potential to show effects of psychotropic drugs on the target organ--the human brain--which could not be previously picked up by single lead recordings."	( Topographic brain mapping of EEG in neuropsychopharmacology--Part II. Clinical applications (pharmaco EEG imaging). Anderer, P; Grünberger, J; Kinsperger, K; Saletu, B, 1987)	0.27
" A dose-response effect was present."	( Caffeinated beverages and decreased fertility. Baird, D; Weinberg, C; Wilcox, A, )	0.13
" When the data were divided into 5 dose levels, there was a dose-response effect: fecundability of the highest consumption group fell to 26% of that of the lowest group."	( Caffeinated beverages and decreased fertility. Baird, D; Weinberg, C; Wilcox, A, )	0.13
" In this study, dosing solutions of seven 14C-radiolabeled compounds representing three chemical classes--organic acid/base [benzoic acid (B), caffeine (C)], organophosphate (OP) pesticides (diisopropylfluorophosphidate, malathion, parathion), and steroid hormones (progesterone, testosterone)--were prepared in ethanol and applied topically at a surface concentration of 40 micrograms cm-2 to the IPPSF."	( The isolated perfused porcine skin flap. III. Percutaneous absorption pharmacokinetics of organophosphates, steroids, benzoic acid, and caffeine. Carver, MP; Riviere, JE; Williams, PL, 1989)	0.68
" In addition, in spontaneous locomotor activity studies, our data show a distinct shift to the right of the caffeine dose-response curve in caffeine pretreated rats."	( Caffeine tolerance: behavioral, electrophysiological and neurochemical evidence. Chou, DT; Forde, J; Hirsh, KR; Khan, S, 1985)	1.92
"Chronic administration of caffeine to mice (1 mg/ml in drinking water X 14 d) led to a downward shift in the dose-response curve for the locomotor effects of caffeine."	( Cross-tolerance studies between caffeine and (-)-N6-(phenylisopropyl)-adenosine (PIA) in mice. Ahlijanian, MK; Takemori, AE, 1986)	0.85
" Under the same treatment conditions, caffeine became a more potent antagonist of PIA-induced analgesia, and the dose-response curve for the locomotor effects of caffeine was shifted to the left."	( Changes in adenosine receptor sensitivity in morphine-tolerant and -dependent mice. Ahlijanian, MK; Takemori, AE, 1986)	0.54
" Each of these three modalities--weight control, alcohol restriction, and sodium restriction--was found to be capable not only of independently controlling blood pressure (particularly in patients with mild hypertension) but also of reducing the number and dosage of prescribed pharmacological agents, should their prescription be indicated."	( Nonpharmacological approaches to the control of high blood pressure. Final report of the Subcommittee on Nonpharmacological Therapy of the 1984 Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. , 1986)	0.27
" The consistent dose-response relations were obtained in cultures treated with mitomycin C, caffeine and colcemid."	( Measurement of micronuclei by cytokinesis-block method in cultured Chinese hamster cells: comparison with types and rates of chromosome aberrations. Sasaki, MS; Wakata, A, 1987)	0.49
" Dose-response curves were determined for each drug by administering cumulative doses IV during timeout periods that preceded sequential components of the FI schedule."	( Psychomotor stimulant effects of methylxanthines in squirrel monkeys: relation to adenosine antagonism. Spealman, RD, 1988)	0.27
"8 microM) was repeatedly dosed with acetylcholine (ACh, 10 microM)."	( The relaxant and spasmogenic effects of some xanthine derivatives acting on guinea-pig isolated trachealis muscle. Boyle, JP; Cortijo, J; Curtis-Prior, PB; Davies, JM; Foster, RW; Hofer, P; Small, RC, 1988)	0.27
" One single drug dose-response experiment or one dose combination of ethanol and caffeine (including the associated control treatments) was run on 4 successive days in 1 week."	( Interaction between ethanol and caffeine in operant behavior of rats. Alder, S; Elsner, J; Zbinden, G, 1988)	0.78
" In CF patients, no correlation was found between caffeine clearance and body weight, height, relative underweight, dosage of pancreatic enzymes, or Chrispin-Norman x-ray score."	( Use of salivary levels to predict clearance of caffeine in patients with cystic fibrosis. Bianchetti, MG; Jost, J; Kraemer, R; Passweg, J; Preisig, R, )	0.64
"Multiple dosage regimens for therapeutic agents are commonly comprised of a constant dosing interval and a constant dose size."	( Predicting caffeine plasma concentrations resulting from consumption of food or beverages: a simple method and its origin. Notari, RE; Pfeifer, RW, 1988)	0.66
" Dosage forms studied were PPA 75 mg sustained-release (SR), PPA SR 75 mg with caffeine 200 mg, caffeine 200 mg, and placebo."	( A controlled clinical trial of the cardiovascular and psychological effects of phenylpropanolamine and caffeine. Noble, R, 1988)	0.72
", complete) so that rats are unresponsive, even to high doses of caffeine, and dose-response curves are displaced downward and flattened; (3) is pharmacologically specific, extending to other methylxanthines but not to nonxanthine psychomotor stimulants."	( Tolerance to behavioral effects of caffeine in rats. Finn, IB; Holtzman, SG, 1988)	0.79
" Random misclassification of coffee and caffeine intake would have the effect of obscuring dose-response relationships to disease incidence."	( Measurement of coffee and caffeine intake: implications for epidemiologic research. Bond, AP; Maffeo, CE; Masters, MN; Robins, M; Schreiber, GB, 1988)	0.84
"We believe that consumers often assume that double the recommended dosage of an OTC drug is safe and more effective."	( A double dose of phenylpropanolamine causes transient hypertension. Chernow, B; Clymer, R; Lake, CR; Quirk, RM; Zaloga, G, 1988)	0.27
" When coadministered with teratogenic dosages of caffeine (1160 to 1290 mumol/kg), L-PIA and chloroadenosine at dosage levels of 1 to 100 mumol/kg did not prevent and in some cases potentiated the teratogenic effects of caffeine."	( Interactions between caffeine and adenosine agonists in producing embryo resorptions and malformations in mice. Clark, RL; Cusick, WA; Eschbach, K; Heyse, JF, 1987)	0.85
"The identification of patients as 'fast acetylators' or 'slow acetylators' is used in clinical practice to help recognize those at risk from toxicity and in guiding the dosage of N-acetylated drugs."	( Caffeine as a potential indicator for acetylator status. Fell, AF; Hudson, SA; Rankin, RB, 1987)	1.72
" MMS and ENU both showed shouldered dose-response curves for exponentially growing asynchronous cells, and the same cell-cycle pattern for synchronous cultures with cells in early S phase being the most sensitive."	( Cell killing by various monofunctional alkylating agents in Chinese hamster ovary cells. Goth-Goldstein, R; Hughes, M, 1987)	0.27
" bolus dosing both separately and concomitantly to New Zealand White rabbits."	( Caffeine and paraxanthine pharmacokinetics in the rabbit: concentration and product inhibition effects. Dorrbecker, BR; Dorrbecker, SH; Ferraina, RA; Kramer, PA, 1987)	1.72
" These effects were sustained for a longer period of time following dosing at a cardioteratogenic level (3."	( The effects of cardioteratogenic doses of caffeine on cardiac function in the 3-day chick embryo. Bruyere, HJ; Folts, JD; Gilbert, EF; Michaud, BJ, 1987)	0.54
"The symptoms of acute poisoning after accidental administration of ten times the usually prescribed dosage of caffeine in a premature infant included the following neurological signs: incessant tremors, hypertonia, continuous opisthotonos posture, whining and crying and digestive disturbances."	( Treatment of caffeine intoxication by exchange transfusion in a newborn. Bonte, JB; Debruyne, D; Lacotte, J; Laloum, D; Moulin, M; Perrin, C, 1987)	0.85
"Pregnant mice were exposed before implantation to caffeine and ethanol to determine the dose-response relation for embryolethality during the preimplantation period."	( Studies on the embryotoxic risk of exposure to caffeine and ethanol during the preimplantation period in the mouse. Granata, I; Krüger, C; Spielmann, H; Tenschert, B; Vogel, R, 1987)	0.78
" Caffeine stimulated locomotor activity of both strains, but the dose-response relationship and time course of drug action differed according to strain."	( Effects of caffeine and L-phenylisopropyladenosine on locomotor activity of mice. Buckholtz, NS; Middaugh, LD, 1987)	1.57
" At a dosage of 20 mg/kg or greater, caffeine counteracts a decrease in social investigation attributed to copulatory experience."	( Caffeine and copulatory experience: interactive effects on social investigatory behavior. Holloway, WR; Thor, DH, 1986)	1.99
" Treatment was continued through 3 wk of serial mating; mating and dosing were terminated concurrently, after which the sires were autopsied and their testes weighed."	( Reproduction study of caffeine administration to male Osborne-Mendel rats. Black, TN; Collins, TF; Gray, GC; Green, S; O'Donnell, M; Welsh, JJ; West, WL; Whitby, KE, 1986)	0.59
" Dose-response data and microcinematographic observations suggest that caffeine induced cardiac anomalies by a direct toxic effect on the embryo rather than by altering cardiac cell function."	( Pulmonary stenosis with ventricular septal defect, common aorticopulmonary trunk, and dextroposition of the aorta: morphologic and qualitative physiologic effects in caffeine-treated chick embryos. Bruyere, HJ; Gilbert, EF; Gilbert, JE; Nishikawa, T; Uno, H, 1986)	0.7
" A consistent dose-response was not found, however, by number of cups of decaffeinated coffee consumed per day."	( A case-control study of factors affecting the development of renal cell cancer. Goodman, MT; Morgenstern, H; Wynder, EL, 1986)	0.27
" Caffeine dosage for all trials was 5 mg/kg body weight."	( Influence of caffeine on exercise performance in habitual caffeine users. Berry, M; Fisher, SM; Forsythe, WA; Mar, MH; McMurray, RG, 1986)	1.55
" Qualitative and quantitative differences in pharmacokinetics and pharmacodynamics of drugs should be considered before dosage regimens can be established."	( [Peculiarities of drug therapy in childhood]. Kusenbach, G; Reinhardt, D, 1986)	0.27
" The elevated blood caffeine levels in breast-fed infants was not related to higher daily dosage of caffeine citrate (4."	( Delay in caffeine elimination in breast-fed infants. Billon, B; Le Guennec, JC, 1987)	1.01
" As yet, formal pharmacokinetics following oral dosing have not been determined."	( Clinical pharmacokinetics of ergotamine in migraine and cluster headache. Perrin, VL, )	0.13
" Regression analysis revealed statistically significant dose-response relationships between peak increases in serum caffeine concentrations and increases in FEV1, FEF25-75%, and Gaw/VL from baseline values."	( Bronchodilator effects of caffeine in coffee. A dose-response study of asthmatic subjects. Gong, H; Hui, KK; Lee, EY; Simmons, MS; Tashkin, DP, 1986)	0.78
"To determine clinical electrophysiologic effects of a moderate dose of caffeine, we compared prevailing cardiac rhythm and rate, the prevalence and frequency of ventricular dysrhythmia, and Q-T intervals in two populations over an initial 24-hour caffeine-free period and a subsequent 24-hour period in which caffeine was ingested in a dosage of 1 mg/kg of body weight at intervals of one half-life during waking hours."	( The effect of caffeine on cardiac rate, rhythm, and ventricular repolarization. Analysis of 18 normal subjects and 18 patients with primary ventricular dysrhythmia. McPherson, DD; Montague, TJ; Renton, KW; Spencer, CA; Sutherland, DJ, 1985)	0.86
" No evidence of a dose-response was noted."	( A case-control study of caffeine and methylxanthines in benign breast disease. Black, M; Funaro, M; Lubin, F; Ron, E; Shitrit, A; Wax, Y, 1985)	0.58
" Urine samples were collected for 24 h after dosing and analysed for caffeine and eleven of its metabolites by high-performance liquid chromatography."	( Comparison of the urinary metabolite profile of caffeine in young and elderly males. Blanchard, J; Jonkman, JH; Sawers, SJ; Tang-Liu, DD, 1985)	0.76
" A dosage of eighty mg/kg/d was more effective than 20 mg/kg/d beta-NF in decreasing malformations, suggesting that stimulation of metabolism and caffeine-induced teratogenicity are inversely related."	( Reduction of caffeine teratogenicity in mice by inducing maternal drug metabolism with beta-naphthoflavone. Randall, JL; Scott, WJ; York, RG, 1985)	0.84
" In each series of experiments, dose-response curves for morphine (probit analysis) were determined with and without the addition of caffeine (30 mg X kg-1)."	( Morphine--caffeine analgesic interaction in rats. Bradley, EL; Brown, PT; Kissin, I; Person, DL; Vinik, HR; Xavier, AV, 1985)	0.88
" Since clearance of caffeine is not related to body weight, these data indicate that a chronic dosing regimen to maintain a given plasma caffeine concentration should not be altered due to obesity."	( Caffeine disposition in obesity. Abernethy, DR; Schwartz, JB; Todd, EL, 1985)	2.04
" With DES, increasing caffeine dosage lengthened the time to first cancer, decreased the number of rats that developed cancers, and decreased the number of cancers overall."	( The inhibitory effect of caffeine on hormone-induced rat breast cancer. Cole, MN; Collins, DC; Petrek, JA; Sandberg, WA; Silberman, MS, 1985)	0.89
" The stimulant effects consisted in delayed intrasession habituation, and they differed in magnitude according to dosage and the complexity of the tunnel arrangements."	( Effects of tunnel maze complexity on caffeinic hyperactivity in the rat. Bättig, K; Martin, JR; Oettinger, R; Rosenberg, E, 1985)	0.27
" Plasma caffeine concentration determined 12 h after administration of the test dosage discriminated best between patients with cirrhosis (5."	( Caffeine elimination: a test of liver function. Kleber, G; Paumgartner, G; Stellaard, F; Wang, T, 1985)	2.15
" Such dose-response relationships may be pertinent to an understanding of phenomena of specific immunological nonresponsiveness and certain types of antigenic competition."	( Antibody formation: reduced responses after administration of excessive amounts of nonspecific stimulators. Braun, W; Ishizuka, M, 1971)	0.25
" Procaine administered in a dosage (5 x 10(-3) W/V)which would suppress the contracture due to caffeine (10 mM), did not modify the tension developed during the hyperpolarization."	( Muscle contraction during hyperpolarizing currents in the crab. García, H; Uchitel, OD, 1974)	0.47
" Therapy for increasing sperm motility includes low dosage androgen and human chorionic gonadotropin."	( Sperm motility. Amelar, RD; Dubin, L; Schoenfeld, C, 1980)	0.26
" Apomorphine, at doses different than the training dose, produced a dose-response relationship, whereas, caffeine (7."	( Caffeine potentiation of apomorphine discrimination. Schechter, MD, 1980)	1.92
" It is concluded that high dosed caffeine causes peripheral insulin resistance in the human being as well as in the experimental animal."	( [Effect of caffeine on various metabolic parameters in vivo]. Förster, H; Sachs, M, 1984)	0.94
" Plasma level determinations after 2 and 6 weeks of treatment revealed that moderately significant correlations existed between AT plasma levels and clinical improvement, dosage intake, age, weight, sex, and coffee intake."	( Tricyclic plasma levels in depressed outpatients treated with amitriptyline. Case, G; Hucker, H; Rickels, K; Weise, C, 1983)	0.27
" The use of non-fasted rats in acute oral toxicity determinations allows both the establishment of relative potency and the estimation of dosage levels for further repeated dose oral studies."	( The effects of fasting on the acute oral toxicity of nine chemicals in the rat. Dashiell, OL; Kennedy, GL, 1984)	0.27
" For example, most patients over age 70 or vegetarian OC users require half the usual dosage of most drugs, whereas smokers and industrial workers require higher than recommended doses."	( Variation in response to drugs: Part II. Environmental and nutritional variables. Fraser, HS; Tibbits, RC, 1983)	0.27
" d-Amphetamine, cocaine, and caffeine each had the effect of elevating both bite and lever press responses; nicotine, chlorpromazine, chlordiazepoxide, and diazepam each elevated lever press responding while depressing bite responding across a portion of the dosage range; phenobarbital, alcohol, and morphine had the effect of depressing both bite and lever press responses but lever pressing was selectively more depressed than biting."	( Unique influences of ten drugs upon post-shock biting attack and pre-shock manual responding. Emley, GS; Hutchinson, RR, 1983)	0.56
" Caffeine pretreatment attenuated amphetamine activity in the rats without producing a horizontal shift in the dose-response curve."	( Caffeine reduces amphetamine-induced activity in asymmetrical interaction. Crumbie, PM; Harkins, D; Haswell, KL; Kassab, CD; White, BC, 1984)	2.62
" Active compounds exhibited an inverted U-shaped dose-response curve."	( Amnesia-reversal activity of a series of N-[(disubstituted-amino)alkyl] -2-oxo-1-pyrrolidineacetamides, including pramiracetam. Butler, DE; L'Italien, YJ; Marriott, JG; Nordin, IC; Poschel, PH; Zweisler, L, 1984)	0.27
" Loss of righting ability was scored at 1, 3, 5 min post dosing and at 5 min intervals thereafter for 20 min."	( Interstrain variation in acute toxic response to caffeine among inbred mice. Carney, JM; Johnson, P; Rennert, OM; Seale, TW, 1984)	0.52
" Dose-response curves for the relaxation of muscle to these drugs were all in parallel."	( Mechanisms of slow contracture induced by potassium and caffeine in skeletal muscle of the dog. Aoyama, T; Ono, H; Sato, T, 1984)	0.51
" Before establishing dosage levels for a chronic toxicity study, the pharmacokinetics of the dose must be determined in the species that will be used in long-term studies."	( The toxicology of cocoa and methylxanthines: a review of the literature. Tarka, SM, 1982)	0.26
"2 SD after dosing with 3H-DHEC (0."	( The effect of caffeine on the absorption of 3H-dihydroergocryptine (DHEC) in the rat. Ballard, SA; Chasseaud, LF; Down, WH, 1980)	0.62
" This potentiation of the fentanyl response peaked at between 0 and 4 hours after dosing and was gone by 72 hours after caffeine dosing."	( Pharmacology, pharmacokinetics, and behavioral effects of caffeine in horses. Greene, EW; Tobin, T; Woods, WE, 1983)	0.72
"0); there was also some evidence of a dose-response relationship in males."	( Coffee drinking and bladder cancer in Connecticut. Marrett, LD; Meigs, JW; Walter, SD, 1983)	0.27
" Dose-response curves were determined for caffeine (6."	( Complete, reversible, drug-specific tolerance to stimulation of locomotor activity by caffeine. Holtzman, SG, 1983)	0.75
" Fifty-one weanling Hartley guinea pigs were divided into five groups which received either procainamide, hydralazine, acetanilide, caffeine or saline sc for 55 weeks; drug dosage was 10 mg/kg initially and was increased incrementally to 40 mg/kg by 10 months except for hydralazine, which was increased to 20 mg/kg."	( Drug-induced antinuclear antibodies in the guinea pig. Balazs, T; Robinson, CJ, 1982)	0.47
" Results indicated that caffeine in low dosage when added to methylphenidate was superior to all other treatment conditions."	( Responses to methylphenidate and varied doses of caffeine in children with attention deficit disorder. Garfinkel, BD; Sloman, L; Webster, CD, 1981)	0.82
" Roasted cocoa freed from fat produced distinctly higher SCE values with a linear dose-response relationship, whereas cocoa butter had no influence on SCE levels."	( Genotoxicity of cocoa examined by microbial and mammalian systems. Münzner, R; Renner, HW, 1982)	0.26
" Ten of the studies are dose-response evaluations."	( Sleep spindles: pharmacological effects in humans. Hirshkowitz, M; Karacan, I; Thornby, JI, 1982)	0.26
" While many agents have been examined for their ability to induce SCE's, complete dose-response information has often been lacking."	( Induction of sister chromatic exchanges and inhibition of cellular proliferation in vitro. I. Caffeine. Guglielmi, GE; Tice, RR; Vogt, TF, 1982)	0.48
" At all three ages responses to increasing caffeine dosage described a curvilinear function in which activity first increased and then decreased."	( Caffeine sensitivity in the neonatal rat. Holloway, WR; Thor, DH, )	1.84
" The dose-response relationships for ethylnitrosourea and 3 chloroethylnitrosourea derivatives were compared with that of 1,3-bis(trans-4-hydroxycyclohexyl)-1-nitrosourea, which is a purely carbamoylating agent."	( Cell killing by various nitrosoureas and the potentiating effect of caffeine. Goth-Goldstein, R, 1982)	0.5
" Caffeine can shift the dose-response curve of chlorpromazine-inhibited sperm motility to right."	( Effects of chlorpromazine and other drugs acting on the central nervous system on human sperm motility. Chaput de Saintonge, DM; Hong, CY; Turner, P, 1982)	1.17
" Differences among high, moderate and low users were common, and some dose-response associations were apparent."	( Somatic manifestations of caffeinism. Greden, JF; Lubetsky, M; Victor, BS, 1981)	0.26
" Rat pups were given either aminophylline, theophylline, or caffeine in a dosage of 40 mg/kg or 80 mg/kg daily from the second postnatal day through 20 days of age."	( A possible effect of the methylxanthines caffeine, theophylline and aminophylline on postnatal myelination of the rat brain. Fuller, GN; Wiggins, RC, 1981)	0.77
" All active compounds gave inverted U-shaped dose-response curves."	( Cognition-activating properties of 3-(Aryloxy)pyridines. Butler, DE; Marriott, JG; Poschel, BP, 1981)	0.26
" Dose-response studies showed that the maximal excretion of urinary PGE and water was obtained by administration of theophylline (50 mg/kg), where the increase in PGE was about 20 times that of the control."	( Effects of methylxanthines on urinary prostaglandin E excretion in rats. Aizawa, Y; Kogo, H; Takeuchi, K, 1981)	0.26
" relative to acetaminophen dosing to inhibit CYP2E1 and CYP1A2, respectively."	( Cytochrome P4502E1 inhibition by propylene glycol prevents acetaminophen (paracetamol) hepatotoxicity in mice without cytochrome P4501A2 inhibition. Loft, S; Poulsen, HE; Roberts, DW; Thomsen, MS, 1995)	0.29
" Forty patients undergoing minor surgical procedures with general anaesthesia were randomly allocated to receive either placebo or caffeine tablets at a dosage equal to their individual average daily caffeine consumption."	( Perioperative administration of caffeine tablets for prevention of postoperative headaches. Drewe, J; Hampl, KF; Rüttimann, U; Schneider, MC; Ummenhofer, W, 1995)	0.78
" Caffeine shifted the dose-response curves of the [Ca2+]i rise induced by vasopressin (0."	( Caffeine inhibits cytosolic calcium oscillations induced by noradrenaline and vasopressin in rat hepatocytes. Berthon, B; Claret, M; Combettes, L, 1994)	2.64
" To search for genes that interact with the Mpk1 pathway, we isolated both chromosomal mutations and dosage suppressor genes that ameliorate the growth-inhibitory effect of overexpressed Mkk1P386."	( Yeast RLM1 encodes a serum response factor-like protein that may function downstream of the Mpk1 (Slt2) mitogen-activated protein kinase pathway. Irie, K; Matsumoto, K; Watanabe, Y, 1995)	0.29
" However, more research needs to be done to determine optimal dosing and tolerability."	( Safety and efficacy of caffeine-augmented ECT in elderly depressives: a retrospective study. Grossberg, GT; Kelsey, MC, 1995)	0.6
" This was done by determining the dose-response functions for turning behavior induced by caffeine, by six other methylxanthine adenosine antagonists and by CGS 15943 [9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo[1,5- c]quinazolin-5-imine], a potent nonxanthine adenosine antagonist; 2) to determine if selective dopamine receptor antagonist block caffeine-induced rotational behavior; and 3) to determine if tolerance develops to caffeine-induced rotational behavior as it does to caffeine-induced stimulation of locomotor activity."	( Does adenosine receptor blockade mediate caffeine-induced rotational behavior? Garrett, BE; Holtzman, SG, 1995)	0.78
" The NECA dose-response curve is multiphasic (depression, stimulation and then depression) versus amphetamine in control mice, but only depressant versus amphetamine in chronic caffeine mice, while being multiphasic versus cocaine in both control and chronic caffeine mice."	( Effects of chronic caffeine on adenosine, dopamine and acetylcholine systems in mice. Daly, JW; Jacobson, KA; Nikodijević, O; Shi, D, )	0.65
" The use of caffeine containing drugs in obese subjects does not necessitate significant dosage modification."	( Caffeine pharmacokinetics in obesity and following significant weight reduction. Berry, EM; Caraco, Y; Levy, M; Zylber-Katz, E, 1995)	2.11
" No differences were found in endurance performance between the three caffeine dosages which indicates that no dose-response relation of caffeine and endurance performance was found."	( The effect of different dosages of caffeine on endurance performance time. de Haan, A; Jeukendrup, AE; Pasman, WJ; van Baak, MA, 1995)	0.8
" Stimulatory effects of injected caffeine were lower in chronically treated mice and the biphasic dose-response (stimulatory followed by depressant) curve for injected caffeine was left shifted."	( Locomotor activity in mice during chronic treatment with caffeine and withdrawal. Daly, JW; Jacobson, KA; Nikodijević, O, 1993)	0.81
"5 mg/ml for 16 h) that reduced the plating efficiency (PE) by 20%, caffeine was not itself a significant mutagen, but it increased by approximately twofold the slope of the dose-response curve for induction of S1- mutants by 137Cs gamma radiation."	( Mutant quantity and quality in mammalian cells (AL) exposed to cesium-137 gamma radiation: effect of caffeine. McGuinness, SM; Shibuya, ML; Ueno, AM; Vannais, DB; Waldren, CA, 1995)	0.74
" In contrast, smokers were much more likely to drink caffeinated coffee, and a dose-response relationship between caffeine from coffee and smoking intake was observed."	( Caffeinated coffee and tea intake and its relationship to cigarette smoking: an analysis of the Second National Health and Nutrition Examination Survey (NHANES II). Klesges, LM; Klesges, RC; Ray, JW, 1994)	0.5
" Based on single-dose caffeine studies, a similar dose-response effect has been hypothesized on performance, alertness and mood during sleep loss."	( The use of caffeine versus prophylactic naps in sustained performance. Arand, DL; Bonnet, MH; Gomez, S; Wirth, O, 1995)	1
" Thus, it was concluded that the dose-response relationships are rather shallow and heterogeneous and that the different parameters have different ranges in which they are sensitive to caffeine."	( Acute dose-effect relationships of caffeine and mental performance, EEG, cardiovascular and subjective parameters. Bättig, K; Hasenfratz, M, 1994)	0.76
" We hypothesized that an intravenous draflazine dosage without effect on hemodynamic and neurohumoral parameters would still be able to augment the forearm vasodilator response to intraarterially infused adenosine."	( Hemodynamic and neurohumoral effects of various grades of selective adenosine transport inhibition in humans. Implications for its future role in cardioprotection. De Abreu, RA; Rongen, GA; Smits, P; Thien, T; Van Belle, H; Ver Donck, K; Willemsen, JJ, 1995)	0.29
" The dose-response trends also followed different patterns in the two groups of subjects."	( Effects of caffeine on perceptual judgment. Dubey, GP; Gupta, BS; Gupta, U, 1994)	0.68
" Cytochrome P-450 1A2 activity was monitored by means of the 13C-[N3-methyl]caffeine breath test and by means of plasma caffeine clearance before omeprazole treatment with 120 mg/day, on the seventh day of dosage and after a 7-day washout."	( Specific and dose-dependent enzyme induction by omeprazole in human beings. Brösicke, H; Heinemeyer, G; Roots, I; Rost, KL, 1994)	0.52
"A commercially available automated enzyme-multiplied immunoassay technique (EMIT) was used to determine serum caffeine concentration after oral and IV administrations of caffeine at dosage of 5 mg/kg of body weight to 12 clinically normal dogs."	( Application of an enzyme-multiplied immunoassay technique for determination of caffeine elimination kinetics as a test of liver function in clinically normal dogs. DeGraves, FJ; Golden, DL; Spano, JS; Whatley, EM; Wilson, RC, 1994)	0.73
" For concentrations of eugenol in the upper range of the dose-response curve (10 mM), the contracture was independent of the Ca++ concentration in the medium."	( Effects of eugenol on excitation-contraction coupling in skeletal muscle. Coelho-de-Souza, AN; Figueiredo, IM; Leal-Cardoso, JH; Souza, IT, )	0.13
" Dose-response curves indicated that, whereas caffeine and theophylline were equally effective at reversing escape deficits, amphetamine not only failed to improve performance in preshocked rats but retarded escape in restrained (no-shock) controls."	( Stress and adenosine: I. Effect of methylxanthine and amphetamine stimulants on learned helplessness in rats. Chang, WC; Minor, TR; Winslow, JL, 1994)	0.55
") 2 h after Fen application, a strong synergism could be seen in the late treatment period as shown by the dose-response curves and by statistical analysis using the principle of least squares."	( Potentiation by caffeine of the frequencies of chromosomal aberrations induced by chronic exposure to fenfluramine in mice. Agarwal, K; Mukherjee, A; Sen, S; Sharma, A, 1994)	0.63
" Prenatal caffeine at the dosage we have used in combination with malnutrition may produce lasting metabolic alterations in the nervous system related to the emergence of suckling behavior and general motor activity."	( Combined effects of caffeine and malnutrition during pregnancy on suckling behavior in newborn rats. Joseph, F; Nakamoto, T; Narayanan, CH; Saito, T; Yoshino, S, 1994)	1.01
" In drug interaction test sessions caffeine (56 mg/kg) blocked the discriminative stimulus properties of the training dose of CDP and shifted the CDP discriminative dose-response function to the right."	( Perceptual masking of the chlordiazepoxide discriminative cue by both caffeine and buspirone. Gauvin, DV; Holloway, FA; Peirce, JM, 1994)	0.8
"05) higher CA-derived radioactivity was seen in maternal brain, carcass and heart as well as placenta and fetal heads and bodies 6 hr after dosing with CA in DMSO compared to CA in DW."	( Alteration in the tissue retention of [14C]-caffeine in pregnant mice by dimethylsulfoxide. Gross, SM; Reddy, CS; Reddy, RV, 1993)	0.55
" PE shifted the ouabain dose-response curve toward lower ouabain concentrations; conversely, ouabain shifted the PE dose-response curve toward lower PE concentrations."	( Nanomolar ouabain augments caffeine-evoked contractions in rat arteries. Blaustein, MP; Heidrich, J; Podberesky, DJ; Weiss, DN, 1993)	0.58
" Cumulative dose-response curves for chlordiazepoxide were obtained before and during chronic chlordiazepoxide administration and during chronic saline administration."	( Tolerance to the behavioral effects of chlordiazepoxide: pharmacological and biochemical selectivity. Alastra, AJ; Cohen, C; Goldberg, SR; Marley, RJ; Sannerud, CA; Serdikoff, SL, 1993)	0.29
" Following dosing with caffeine no change in the distribution of staining for hsp 90, 70 and 25 was found."	( Immunohistochemical localisation of the 90, 70 and 25 kDa heat shock proteins in control and caffeine treated rat embryos. Pollard, I; Wilkinson, JM, 1993)	0.82
" Cumulative dosing tests for the discriminative stimulus properties consisted of two to five trials of FR20 schedule; responses for both levers were reinforced."	( [Discriminative stimulus properties of ephedra herb (Ephedra sinica) in rats]. Furuya, I; Watanabe, S, 1993)	0.29
"This study examined the dose-response effects of caffeine on plasma K+ balance during prolonged exercise."	( Caffeine attenuates the exercise-induced increase in plasma [K+] in humans. Graham, TE; Lindinger, MI; Spriet, LL, 1993)	1.98
" Concomitant use of these agents, even when dosed several hours apart, should be avoided."	( Drug-drug interactions with fluoroquinolones. Marchbanks, CR, )	0.13
" Furthermore, we were able to demonstrate that the dose-response relation in single cells shows an all-or-none feature, which seems at least partly due to the feedback control of Ca2+ release."	( [Ca2+ release mechanism studied in single isolated smooth muscle cells]. Endo, M; Iino, M; Yamazawa, T, 1993)	0.29
" In seated, unanesthetized monkeys prepared with a head plethysmograph, ventilation during exposure to air, CO2 (3, 4 and 5%) mixed in air (hypercapnia), 10% O2 mixed in N2 (hypoxia) and 100% O2 (hyperoxia) was measured during cumulative dosing with each drug."	( Effects of adenosine agonists on ventilation during hypercapnia, hypoxia and hyperoxia in rhesus monkeys. Howell, LL, 1993)	0.29
" Embryos were removed 3 h after dosing on gestation day (GD) 9, 10, 11 and 12 and total embryonic protein and RNA analysed."	( Caffeine does not increase synthesis of heat shock proteins in rat embryos. Hiller, RG; Li, K; Pollard, I; Walsh, DA; Wilkinson, JM, 1993)	1.73
" Questions remain with regard to the identification and determinants of either responsive or sensitive subgroups, dose-response relationships, and the effects of parent-teacher expectancies on behavioral ratings."	( Behavioral and cognitive effects of methylxanthines. A meta-analysis of theophylline and caffeine. Bender, BG; Krasowski, M; Leventhal, BL; Phillips, W; Stein, MA, 1996)	0.52
" The objective of this study was to validate urine caffeine metabolite ratios versus stable isotope-labeled caffeine clearance under different caffeine dosing conditions."	( Validation of urine caffeine metabolite ratios with use of stable isotope-labeled caffeine clearance. Benowitz, NL; Denaro, CP; Jacob, P; Wilson, M, 1996)	0.87
" The stable isotope technique allowed simultaneous oral dosing of caffeine and measurement of caffeine metabolite ratios and caffeine clearance, the latter reflecting CYP1A2 activity."	( Validation of urine caffeine metabolite ratios with use of stable isotope-labeled caffeine clearance. Benowitz, NL; Denaro, CP; Jacob, P; Wilson, M, 1996)	0.85
" The dose-response curve for GCV appeared more exponential, without a threshold, but with a no-effect dose of around 150 mumols/kg per day."	( Comparative in-vivo genotoxicity of antiviral nucleoside analogues; penciclovir, acyclovir, ganciclovir and the xanthine analogue, caffeine, in the mouse bone marrow micronucleus assay. Haynes, P; Lambert, TR; Mitchell, ID, 1996)	0.5
" Simulations based on these results indicated that the current dosage guidelines of 20 mg/kg loading dose of caffeine citrate followed by a 5 mg/kg/day maintenance dose should achieve concentrations within the traditional target range in > 70% of neonates."	( Population pharmacokinetics of caffeine in neonates and young infants. Kerr, S; Thomson, AH; Wright, S, 1996)	0.79
" Dose-response curves on the production of inositol-1,4,5-trisphosphate and Ca2+ by ATP and UTP were consistently similar."	( Expression cloning and signal transduction pathway of P2U receptor in mammary tumor cells. Enomoto, K; Furuya, K; Maeno, T; Moore, RC; Oka, T; Yamagishi, S, )	0.13
" Furthermore, among women with a high intake of caffeine a dose-response relationship was found; women smoking one to five cigarettes per day had no increased risk of preterm birth compared with nonsmokers with the same intake of caffeine, women smoking six to ten cigarettes per day had almost three times higher risk of preterm birth, and women smoking more than 10 cigarettes per day had almost five times higher risk of preterm birth compared with nonsmokers with the same intake of caffeine."	( Smoking during pregnancy and preterm birth. Hedegaard, M; Henriksen, TB; Secher, NJ; Wisborg, K, 1996)	0.55
" The dose-response curve (DRC) method of Pöch permitted an extensive evaluation of the kind (additivity or independence) of interactions occurring in combined drug effects."	( Alprazolam, caffeine and their interaction: relating DRL performance to pharmacokinetics. Lau, CE; Wang, J, 1996)	0.67
" Plasma concentrations were measured in four additional animals of all high dose groups after the last dosing at seven time points."	( Studies on the chronic oral toxicity of an analgesic drug combination consisting of acetylsalicylic acid, paracetamol and caffeine in rats including an electron microscopical evaluation of kidneys. Bauer, E; Bauer, M; Greischel, A; Hirsch, U; Lehmann, H; Schmid, J; Schneider, P, 1996)	0.5
" Dose-response curves of non inactivated and inactivated NMDA responses showed that the apparent receptor affinity for NMDA is not different under the two conditions."	( Ca(2+)-dependent inactivation of NMDA receptors: fast kinetics and high Ca2+ sensitivity in rat dorsal horn neurons. Albuquerque, C; Gu, J; Kyrozis, A; MacDermott, AB, 1996)	0.29
" The dose-response curves suggest that TG was more efficient than CPA and that both drugs were more efficient in 7-day- than in 2-day-old cells."	( Effects of thapsigargin and cyclopiazonic acid on intracellular calcium activity in newborn rat cardiomyocytes during their development in primary culture. Gomez, JP; Potreau, D, 1996)	0.29
"05) dose-response relationship."	( Analgesic efficacy of paracetamol and its combination with codeine and caffeine in surgical pain--a meta-analysis. Li Wan Po, A; Zhang, WY, 1996)	0.53
" The dosage was gradually decreased from week 12 to discontinuation at week 39."	( The effect of ephedrine plus caffeine on smoking cessation and postcessation weight gain. Iversen, E; Jakobsen, HB; Jørgensen, S; Mikkelsen, KL; Nørregaard, J; Søeberg, B; Sørensen, T; Tønnesen, P, 1996)	0.59
"5 microm) of cADPR shifted the dose-response curve of caffeine-induced 45Ca2+ release to the left."	( Characterization of ryanodine-sensitive Ca2+ release from microsomal vesicles of rat parotid acinar cells: regulation by cyclic ADP-ribose. Nishiyama, A; Ozawa, T, 1997)	0.55
"The relationship between the plasma oxypurinol (the active metabolite of allopurinol) concentration at the midpoint of each caffeine dosage interval and the decrement in the urinary 1MX to 1MU ratio fitted well by a sigmoid Emax model."	( 1-Methylxanthine derived from caffeine as a pharmacodynamic probe of oxypurinol effect. Birkett, DJ; Day, RO; Lillywhite, KJ; Miners, JO; Valente, L, 1997)	0.79
" A dose-response to varying concentrations of bitter tastants can be measured."	( Response of pigs to bitter-tasting compounds. Nelson, SL; Sanregret, JD, 1997)	0.3
" In this dose-response study, we investigated the effects of blindly administered intravenous caffeine (3, 5, and 7 mg/kg) versus placebo in normal control subjects."	( Dose-response effects of intravenous caffeine in normal volunteers. Nickell, PV; Uhde, TW, )	0.62
" Thus, at low doses of MMC, FA-C cells exhibit a unique cyclin B1/cdc2 response that is not observed in wild-type cells treated with an equitoxic high dosage of cross-linker."	( Involvement of the Fanconi's anemia protein FAC in a pathway that signals to the cyclin B/cdc2 kinase. Arwert, F; Dijkmans, LM; Joenje, H; Kruyt, FA, 1997)	0.3
" The interaction was PK linked and mainly not distinguishable from independence as indicated by the Poch dose-response curve method and the integration of PK and pharmacodynamics."	( Differential reinforcement of low rate performance, pharmacokinetics and pharmacokinetic-pharmacodynamic modeling: independent interaction of alprazolam and caffeine. Falk, JL; Lau, CE; Wang, Y, 1997)	0.49
" MHEh muscles revealed a dose-response curve similar to that found in MHN specimens."	( Classification of malignant hyperthermia-equivocal patients by 4-chloro-M-cresol. Bittner, RE; Fricker, R; Gilly, H; Kress, HG; Musat, I; Steinbereithner, K, 1997)	0.3
" Initially, in phase I, 18 experiments were performed to study the dose-response curve of both the drugs."	( Combined effects of caffeine and nicotine on cardiovascular hemodynamics in canine model. Billie, M; Jain, AC; Mehta, MC, 1997)	0.62
" Routinely determining human acetylate phenotype status might be helpful in adjusting and modifying dapsone dosage regimen."	( Relationship between high incidence of adverse dapsone reactions and slow acetylate phenotype or low plasma/lymphocyte glutathione level. Guo, R; Lauterberg, B; Thormann, W, 1996)	0.29
" CS contracts the smooth muscle of the aorta in a dose-response relation."	( Vasoconstrictor effect of Cissus sicyoides on guinea-pig aortic rings. Cartas-Heredia, L; García, X; Gijón, E; Lorenzana-Jímenez, M, 1997)	0.3
" Acute alprazolam and caffeine dose-response curves (DRCs) were characterized and were then used to determine the maintenance dose for the respective chronic dose regimens."	( Independent interaction of alprazolam and caffeine under chronic dose regimens on differential reinforcement of low-rate (DRL 45-s) performance. Falk, JL; Lau, CE; Wang, Y, 1997)	0.88
" A significant increase in IOP was noted 15 min and 1 hr after a single dosing of caffeine alone."	( Relationship between caffeine-induced ocular hypertension and ultrastructure changes of non-pigmented ciliary epithelial cells in rats. Ando, T; Kurata, K; Maeda, M; Nishida, E; Suzuki, T; Tokuriki, M; Tsukuda, R, 1997)	0.84
" The dosage of sertraline ranged from 25 to 150 mg/day (93."	( The extent and determinants of changes in CYP2D6 and CYP1A2 activities with therapeutic doses of sertraline. Herrmann, N; Kalow, W; Naranjo, CA; Ozdemir, V; Reed, K; Sellers, EM; Shulman, RW, 1998)	0.3
" Thus, from the present study it may be concluded that: (a) caffeine-induced stimulation of LA is dependent on dose and duration of caffeine treatment, (b) development of tolerance to caffeine is dependent on the dosage of caffeine, and (c) the reduction of central GABAergic activity in the caffeine-nontolerant condition pushed up and restored the LA to the control level on the development of tolerance to caffeine."	( Is GABA involved in the development of caffeine tolerance? Mukhopadhyay, S; Poddar, MK, 1998)	0.81
" Propofol but not ketamine, however, caused a leftward shift in the dose-response curve to extracellular Ca2+ for shortening, with no concomitant effect on peak [Ca2+]i."	( Propofol and ketamine only inhibit intracellular Ca2+ transients and contraction in rat ventricular myocytes at supraclinical concentrations. Damron, DS; Kanaya, N; Murray, PA, 1998)	0.3
"Many studies have failed to determine a systematic dose-response relationship across different cognitive tasks between caffeine and EEG power spectra."	( Quadratic dose-response relationship between caffeine (1,3,7-trimethylxanthine) and EEG correlation dimension. Martin, F; Schreter, Z; Watters, PA, 1998)	0.77
" The methylxanthines were continued at least until discharge from the NICU and the dosage altered to keep the levels within the therapeutic range."	( Comparison of the effects of theophylline and caffeine on serum erythropoietin concentration in premature infants. Fang, S; Gamsu, HR; Greenough, A; Marsden, JT; Peters, TJ; Sherwood, RA, 1998)	0.56
" No dose-response relationship was found among smokers."	( Caffeine intake and fecundability: a follow-up study among 430 Danish couples planning their first pregnancy. Bonde, JP; Ernst, E; Giwercman, A; Henriksen, TB; Hjollund, NH; Jensen, TK; Kolstad, H; Olsen, J; Scheike, T; Skakkebaek, NE, )	1.57
" No such dose-response relationship was detected among smokers."	( Caffeine intake and fecundability: a follow-up study among 430 Danish couples planning their first pregnancy. Bonde, JP; Ernst, E; Giwercman, A; Henriksen, TB; Hjollund, NH; Jensen, TK; Kolstad, H; Olsen, J; Scheike, T; Skakkebaek, NE, )	1.57
" The same dosage of caffeine was given to 10 premenopausal white women during the midfollicular and midluteal phases of three complete menstrual cycles."	( Quantitation of three-month intraindividual variability and influence of sex and menstrual cycle phase on CYP1A2, N-acetyltransferase-2, and xanthine oxidase activity determined with caffeine phenotyping. Bertino, JS; Gotschall, R; James, AW; Kashuba, AD; Kearns, GL; Leeder, JS; Nafziger, AN, 1998)	0.82
"In order to investigate the possible mechanisms for caffeine-induced ocular hypertension, the intraocular pressure (IOP) and the outflow through the trabecular meshwork were measured in beagle dog eyes after dosing with intravenous caffeine (30 mg/kg) alone or in combination with the topical beta-blocker befunolol [applied as 100 microliters of a 1% (w/v) solution] which inhibits aqueous humor formation in the ciliary body."	( Aqueous humor dynamics in beagle dogs with caffeine-induced ocular hypertension. Ando, T; Fujimoto, H; Kurata, K; Suzuki, T; Tokuriki, M; Tsukuda, R, 1998)	0.81
" The dose-response relationship for cocaine demonstrated a a typical inverted U-shaped function."	( Reinforcing effects of caffeine, ephedrine, and their binary combination in rats. Baird, TJ; Briscoe, RJ; Gauvin, DV; Holloway, FA; Vallett, M; Vanecek, SA, 1998)	0.61
"The aim of the study was to investigate the dose-response relationship for psychomotor performance, caffeine and theophylline in healthy elderly volunteers."	( Psychomotor performance: investigating the dose-response relationship for caffeine and theophylline in elderly volunteers. Bryant, CA; Farmer, A; Jackson, SH; Keating, J; Sherwood, R; Swift, CG; Tiplady, B, 1998)	0.75
" Among men no dose-response association was found after control for confounders including women's alcohol intake."	( Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy. Bonde, JP; Ernst, E; Giwercman, A; Henriksen, TB; Hjollund, NH; Jensen, TK; Kolstad, H; Olsen, J; Scheike, T; Skakkebaek, NE, 1998)	0.3
" No dose-response relationship was found in male partners after adjustment for the same confounders."	( Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy. Bonde, JP; Ernst, E; Giwercman, A; Henriksen, TB; Hjollund, NH; Jensen, TK; Kolstad, H; Olsen, J; Scheike, T; Skakkebaek, NE, 1998)	0.3
" Doses of (-)ephedrine and caffeine, which produced < or = 1% drug-appropriate responding when administered alone, were able to enhance each other's stimulus effects when administered in combination such that there was a twofold leftward shift in their respective dose-response curves."	( (-)Ephedrine and caffeine mutually potentiate one another's amphetamine-like stimulus effects. Gabryszuk, M; Glennon, RA; Young, R, 1998)	0.94
" This result is consistent with previous findings indicating a flat dose-response relationship for the psychoactive effects of caffeine; and because of the adverse effects (e."	( Mood and psychomotor performance effects of the first, but not of subsequent, cup-of-coffee equivalent doses of caffeine consumed after overnight caffeine abstinence. Robelin, M; Rogers, PJ, 1998)	0.72
" For example, the frequency and duration of 'moving' dose-dependently increased after cocaine, while d-amphetamine and caffeine again produced bell-shaped dose-response curves."	( D-amphetamine, cocaine and caffeine: a comparative study of acute effects on locomotor activity and behavioural patterns in rats. Antoniou, K; Hyphantis, T; Kafetzopoulos, E; Marselos, M; Papadopoulou-Daifoti, Z, 1998)	0.81
" In phase I, 30 experiments were performed in our laboratories to study the dose-response curves of both the drugs."	( Combined effects of caffeine and alcohol on hemodynamics and coronary artery blood flow in dogs. Billie, M; Jain, AC; Mehta, MC, 1999)	0.63
" Perifusion of young and senescent AP cells with thymulin doses, ranging from 10(-8) to 10(-5) M, gave a logarithmic dose-response pattern of GH."	( Growth hormone-releasing activity of thymulin on pituitary somatotropes is age dependent. Brown, OA; Dardenne, M; Goya, RG; Pléau, J; Sosa, YE, 1999)	0.3
" Samples were collected before and for 24 hours after caffeine dosing for the determination of caffeine in plasma and 1,7-dimethylxanthine, 3,7-dimethylxanthine, 1,7-dimethyluric acid (17U), 1-methylxanthine (1X) and 1-methyluric acid (1U), and 5-acetylamino-6-amino-3-methyluracil (AAMU) in urine."	( Effect of venlafaxine on CYP1A2-dependent pharmacokinetics and metabolism of caffeine. Albano, D; Amchin, J; Klockowski, PM; Taylor, KP; Zarycranski, W, 1999)	0.78
"The template release kinetics of theophylline molecularly imprinted polymers has been examined with a view to determining their potential as a controlled release drug dosage form."	( Theophylline molecularly imprinted polymer dissociation kinetics: a novel sustained release drug dosage mechanism. Andersson, HS; Nicholls, IA; Norell, MC, 1998)	0.3
" Therefore, the objective of this study was to assess the effects of a clinically relevant dosage of caffeine on the stereoselective disposition of mexiletine."	( Stereoselective disposition of the antiarrhythmic agent mexiletine during the concomitant administration of caffeine. Abolfathi, Z; Gilbert, M; Labbé, L; Robitaille, NM; St-Maurice, F; Turgeon, J, 1999)	0.73
" Transfected cells were dosed with several known inducers of CYP3A4 and the levels of SPAP were measured."	( A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro. Gibson, GG; Goldfarb, PS; Gray, TJ; Ogg, MS; Tarbit, M; Williams, JM, 1999)	0.3
" Caffeine dosing before exercise delays fatigue and may enhance performance of high-intensity exercise."	( Effective nutritional ergogenic aids. Applegate, E, 1999)	1.21
"The productivity of Drosophila prosaltans treated with six concentrations of caffeine (from 50 micrograms/ml to 2,500 micrograms/ml of culture medium) during ten generations (approximately 8 months) decreased in a dosage dependent manner in every generation, but at the end of the treatment the flies in all experiments recovered normal productivity, except for those treated with 2,500 micrograms/ml."	( The development of resistance to caffeine in Drosophila prosaltans: productivity and longevity after ten generations of treatment. Bicudo, HE; Itoyama, MM; Manzato, AJ, 1998)	0.81
" All-or-none Ca(2+) waves obtained with increasing concentrations of norepinephrine were transformed in a dose-response relationship with a Hill coefficient close to unity after ryanodine receptor inhibition."	( Norepinephrine-induced Ca(2+) waves depend on InsP(3) and ryanodine receptor activation in vascular myocytes. Boittin, FX; Halet, G; Macrez, N; Mironneau, J, 1999)	0.3
" The type of fibres (type I: oxidative, slow; type II: glycolytic, fast) were determined with strontium dose-response curves."	( [Caffeine skinned fiber tension test: application to the diagnosis of susceptibility to malignant hyperthermia]. Adnet, P; Börtlein, ML; Etchrivi, T; Haudecoeur, G; Krivosic-Horber, R; Nivoche, Y; Tavernier, B, 1999)	1.21
" They also received the experimental diets containing one of test compounds (500 ppm) for 5 weeks, starting one week before the first dosing of AOM."	( Inhibition of azoxymethane-induced aberrant crypt foci in rats by natural compounds, caffeine, quercetin and morin. Honjo, S; Kawabata, K; Kohno, H; Matsunaga, K; Murakami, M; Shimada, R; Shimizu, M; Tanaka, T; Yamada, Y, )	0.36
" The presence of exogenously added CaM (10 microg/ml) markedly increased the caffeine (5-10 mM)-induced (45)Ca(2+) release and shifted the dose-response curve of caffeine-induced (45)Ca(2+) release to the left."	( Ryanodine-sensitive Ca(2+) release mechanism of rat pancreatic acinar cells is modulated by calmodulin. Ozawa, T, 1999)	0.53
" Based on the data supplied, these threshold concentrations could effectively control orally administered caffeine in racehorses, up to the dosage used in this work, up to 72 h before sampling time."	( The confirmation and control of metabolic caffeine in standardbred horses after administration of theophylline. Herskovits, P; Mendonca, M; Ryan, M; Todi, F, 1999)	0.78
" Caffeine at this dosage level alters cardiovascular dynamics by augmenting arterial blood pressure."	( Influence of caffeine on metabolic and cardiovascular functions during sustained light intensity cycling and at rest. Celik, S; Dorsey, JL; Engels, HJ; Wirth, JC, 1999)	1.58
"The rabbit inferior vena cava (IVC) is a large-capacitance vessel that displays typical contractile dose-response curves for caffeine and phenylephrine (PE)."	( Asynchronous Ca(2+) waves in intact venous smooth muscle. Lee, CH; Poburko, D; Ruehlmann, DO; van Breemen, C, 2000)	0.51
"To establish whether gender or N-acetyltransferase 2 (NAT2) genotype influence the urinary 17 U+17X/137X ratio after dosing with caffeine."	( The effect of NAT2 genotype and gender on the metabolism of caffeine in nonsmoking subjects. Bassendine, MF; Daly, AK; Welfare, MR, 2000)	0.75
" Significant dose-response relationships to caffeine were seen only for SBP, heart rate, and skin temperature."	( The acute physiological and mood effects of tea and coffee: the role of caffeine level. Aspen, J; Lane, J; Moore, KL; O'Brien, DC; Quinlan, PT; Rycroft, JA, 2000)	0.8
" Caffeine also increased the plasma concentrations of pregnenolone and progesterone with a dose-response relation similar to that observed in the brain, whereas the caffeine-induced increase in the plasma concentration of allopregnanolone was maximal at a dose of 50 mg/kg."	( Caffeine-induced increases in the brain and plasma concentrations of neuroactive steroids in the rat. Biggio, G; Concas, A; Porcu, P; Purdy, RH; Serra, M; Sogliano, C, 2000)	2.66
" Volume of distribution and clearance increased with weight, supporting weight-adjusted dosing of caffeine citrate."	( Caffeine citrate for the treatment of apnea of prematurity: a double-blind, placebo-controlled study. Erenberg, A; Haack, DG; Hicks, GM; Leff, RD; Mosdell, KW; Wynne, BA, 2000)	1.97
" However, postimplantation embryo development assessed on Day 12 of gestation revealed that caffeine exposure of 15 and 30 mg kg(-1) significantly reduced, at both dosage levels, somite number and the extent of neural tube closure."	( Maternal caffeine consumption during pregnancy does not affect preimplantation development but delays early postimplantation growth in rat embryos. Jacombs, A; Loupis, A; Pollard, I; Ryan, J, 1999)	0.94
" Furthermore, an increase in cytosolic Ca(2+) activity induced a more marked shift of dose-response curves toward lower concentrations for 4-CmC than caffeine."	( Differential effects of 4-chloro-m-cresol and caffeine on skinned fibers from rat fast and slow skeletal muscles. Choisy, S; Huchet-Cadiou, C; Léoty, C, 2000)	0.76
" two 150-mg doses administered in a decaffeinated/sugar-free cola drink post-baseline and 90 min later) was crossed with nicotine (ad libitum own dosing vs."	( Effects of nicotine and caffeine, separately and in combination, on EEG topography, mood, heart rate, cortisol, and vigilance. Dibb, WD; Gilbert, DG; Hiyane, SG; Plath, LC, 2000)	0.61
" In the fairly extensive literature on the psychostimulant effects of caffeine, there are few dose-response studies and even fewer studies of the effects of doses of caffeine lower than 50 mg (the range of the amounts of caffeine contained in, for example, a typical serving of tea or cola)."	( Effects of low doses of caffeine on cognitive performance, mood and thirst in low and higher caffeine consumers. Rogers, PJ; Smit, HJ, 2000)	0.85
" All doses of caffeine significantly affected cognitive performance, and the dose-response relationships for these effects were rather flat."	( Effects of low doses of caffeine on cognitive performance, mood and thirst in low and higher caffeine consumers. Rogers, PJ; Smit, HJ, 2000)	0.97
" High dosage expression of a truncated mutant of int6(+) conferred a hypersensitivity to caffeine, but did not cause the defect in meiosis."	( Fission yeast Int6 is not essential for global translation initiation, but deletion of int6(+) causes hypersensitivity to caffeine and affects spore formation. Bandyopadhyay, A; Maitra, U; Matsumoto, T, 2000)	0.74
" The ET-1 dose-response curve (1 pM-5 nM) was rightward shifted after preconditioning with adenosine (1 microM) for 20 min and 10 min of washout (n = 11)."	( Adenosine preconditions against endothelin-induced constriction of coronary arterioles. Chilian, WM; Jones, DW; Merkus, D; Nishikawa, Y; Stepp, DW, 2000)	0.31
"Using numerical models and data obtained from in vitro experiments, the dimensions of diffusion controlled release dosage forms to achieve desired in vivo levels are predicted."	( Calculation of the dimensions of dosage forms with release controlled by diffusion for in vivo use. Ainaoui, A; Bodmeier, R; Siepmann, J; Vergnaud, JM, 2001)	0.31
" After drug-induced hepatitis, a caffeine test might be used to check the total recovery or to choose an adapted dosage of medicines."	( Caffeine metabolism differences in acute hepatitis of viral and drug origin. Bechtel, PR; Bechtel, YC; Brientini, MP; David-Laroche, M; Lelouët, H; Miguet, JP; Paintaud, G, )	1.86
" Caffeine, theophylline, and paraxanthine shifted the dose-response curve for adenosine at the A1, A2A, and A2B receptors."	( Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells. Fredholm, BB; Irenius, E; Kull, B; Schulte, G, 2001)	1.22
" The antinociceptive efficacies were evaluated using several dose-response curves and time courses."	( Effect of caffeine on antinociceptive action of ketoprofen in rats. Díaz-Reval, MI; Domínguez-Ramírez, AM; Hernández-Delgadillo, GP; López-Muñoz, FJ; Ventura-Martínez, R, )	0.53
" Simultaneous determination of these three drugs: anorexic, central nervous stimulant and tranquilizer, respectively, in pharmaceutical dosage forms has not been reported."	( Analysis of multicomponent formulations containing phenylpropanolamine hydrochloride, caffeine and diazepam by using LC. Ferreyra, C; Ortiz, C, 2001)	0.53
" The variability in CYP1A2 activity in healthy adults, based on data after oral and intravenous dosage (CLm, CL and AUC), ranged from 34 to 42%."	( Uncertainty factors for chemical risk assessment. human variability in the pharmacokinetics of CYP1A2 probe substrates. Dorne, JL; Renwick, AG; Walton, K, 2001)	0.31
" CYP1A2 phenotyping with a simple caffeine test may contribute to individualization of clozapine dosage and differentiate between treat ment noncompliance and high CYP1A2 activity."	( CYP1A2 activity as measured by a caffeine test predicts clozapine and active metabolite steady-state concentrationin patients with schizophrenia. Afra, P; Albers, LJ; Collins, EJ; Kalow, W; Kennedy, JL; Ozdemir, V; Posner, P; Reist, C; Roy, R; Tang, BK; Walkes, W, 2001)	0.87
" Tolbutamide (CYP2C9), caffeine (CYP1A2), dextromethorphan (CYP2D6), oral midazolam (intestinal wall and hepatic CYP3A), and intravenous midazolam (hepatic CYP3A) were administered before, with short-term St John's wort dosing (900 mg), and after 2 weeks of intake (300 mg 3 times a day) to determine CYP activities."	( The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity. Gorski, JC; Hall, SD; Hamman, MA; Huang, SM; Lesko, LJ; Wang, Z, 2001)	0.62
" The 2 h plasma concentration ratios from studies 1 and 2 were combined and a pooled analysis performed to compare ratios within each study (to determine the change in ratio when MDZ was dosed with and without chlorzoxazone) and between studies (to determine the consistency of the ratios when MDZ was given either as part of the two six drug cocktails or when given alone and as part of the five drug cocktail)."	( An interaction between the cytochrome P450 probe substrates chlorzoxazone (CYP2E1) and midazolam (CYP3A). Dickins, M; Gibson, A; Palmer, JL; Pleasance, S; Scott, RJ, 2001)	0.31
"According to the degree of importance to the combined analgesic effect, Ace > Caf > Bul; Ace showed a significant dose-response relationship, whereas in Caf and Bul, this relationship was not apparent."	( Quantitative design of optimal analgesic combination of acetaminophen, caffeine, and butalbital. Gui, CQ; Sun, RY; Wang, XW; Zheng, QS, 2001)	0.54
" The caffeine was fed via the animals' dietary water and the dosage was 10 mg/100 g body weight per day, 3 days a week."	( Effects of caffeine and exercise on the development of bone: a densitometric and histomorphometric study in young Wistar rats. Hsieh, SS; Huang, TH; Liu, SH; Yang, RS, 2002)	1.22
" With increasing caffeine dosage the level of reported visual disturbances increased."	( The effect of caffeine ingestion on the perceived instability of visual patterns. Coren, S, 2002)	1.01
" Subjects consisted of 84 (n=12 per group); healthy, non-smoking, males who had abstained from caffeine ingestion for at least 20 h prior to dosing and were randomly assigned to the treatment groups."	( The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers. Balkin, TJ; Belenky, GL; Cox, DS; Eddington, ND; Kamimori, GH; Karyekar, CS; Otterstetter, R, 2002)	0.78
" One EM subject had a very low oral clearance of fluvoxamine after both single and multiple dosing of the drug."	( Low daily 10-mg and 20-mg doses of fluvoxamine inhibit the metabolism of both caffeine (cytochrome P4501A2) and omeprazole (cytochrome P4502C19). Andersson, K; Bertilsson, L; Carrillo, JA; Christensen, M; Dahl, ML; Mihara, K; Ramos, SI; Tybring, G; Yasui-Furokori, N, 2002)	0.54
" The dose-response curves of caffeine-induced calcium release of nEGFP-RYR(FL) differ from those of the truncated nEGFP-RYR(Bhat)."	( Functional properties of EGFP-tagged skeletal muscle calcium-release channel (ryanodine receptor) expressed in COS-7 cells: sensitivity to caffeine and 4-chloro-m-cresol. Moccagatta, L; Pouliquin, R; Treves, S; Zorzato, F, 2002)	0.81
"The dosing regimen studied was suitable for our local Asian neonates as it resulted in therapeutic caffeine concentrations for adequate treatment of apnoea."	( Caffeine in apnoeic Asian neonates: a sparse data analysis. Chirino-Barcelo, Y; Khoo, YM; Lee, HS; Ong, D; Tan, KL, 2002)	1.97
" The adverse events accompanying acute dosing are mild and transient."	( The safety and efficacy of pharmaceutical and herbal caffeine and ephedrine use as a weight loss agent. Greenway, FL, 2001)	0.56
" Baseline tone, electrical field stimulation (EFS)-induced nitric oxide-mediated off responses, and changes in the cholecystokinin (CCK)-8 dose-response relationship were measured."	( The effect of phosphodiesterase inhibition on gallbladder motility in vitro. Conklin, JL; Cullen, JJ; Hinkhouse, MM; Lindaman, BA, 2002)	0.31
" Caffeine (10(-5) M) and EHNA increased the CCK-8 dose-response contractions."	( The effect of phosphodiesterase inhibition on gallbladder motility in vitro. Conklin, JL; Cullen, JJ; Hinkhouse, MM; Lindaman, BA, 2002)	1.22
" The developed method is rapid and sensitive and therefore suitable for routine control of these drugs in dosage form."	( HPLC assay of acetylsalicylic acid, paracetamol, caffeine and phenobarbital in tablets. Agbaba, D; Aleksic, M; Eric, S; Franeta, JT; Pavkov, S; Vladimirov, S, 2002)	0.57
" However, effects of proconvulsants must be reconciled with increasing evidence of the importance of stimulus dosing relative to seizure threshold and other parameters, now considered key to the efficacy of ECT."	( Augmentation of seizure induction in electroconvulsive therapy: a clinical reappraisal. Caroff, SN; Datto, C; Ilivicky, HJ; Rai, AK, 2002)	0.31
" The dose-response relationship of caffeine-induced inhibition of cAMP-PDEs was not correlated with the stimulation of insulin secretion."	( Ryanodine receptors of pancreatic beta-cells mediate a distinct context-dependent signal for insulin secretion. Ahmed, M; Bruton, JD; Frame, M; Furman, BL; Islam, MS; Lemmens, R; Persson-Sjögren, S; Pyne, NJ; Shi, CL; Westerblad, H, 2003)	0.6
" FFTs of raw signals were generated at baseline (predose) and after intraperitoneal dosing of the rats with atropine (30 min postdose; 6 mg/kg), caffeine (90 and 150 min postdose; 30 mg/kg), ketamine (15 and 30 min postdose; 50 mg/kg), and pentobarbarbital (60 and 90 min postdose; 40 mg/kg)."	( Development of a quantitative method for evaluation of the electroencephalogram of rats by using radiotelemetry. Cain, C; Fitzgerald, AL; Juneau, P; Southwick, K, 2003)	0.52
" For combined treatment with caffeine and paclitaxel, added caffeine reduced the cytotoxic effect of paclitaxel not only in dose-response but also in time-response curves."	( Caffeine diminishes cytotoxic effects of paclitaxel on a human lung adenocarcinoma cell line. Akimoto, T; Kitamoto, Y; Mitsuhashi, N; Nakano, T; Sakurai, H, 2003)	2.05
" Dosing occurred 72 h after training commenced."	( Caffeine effects on marksmanship during high-stress military training with 72 hour sleep deprivation. Lieberman, HR; Shukitt-Hale, B; Tharion, WJ, 2003)	1.76
"0 mg/ml) resulted in tolerance to the motor effects of an acute administration of caffeine, lack of tolerance to amphetamine, apparent tolerance to MSX-3 (shift to the left of its 'bell-shaped' dose-response curve), and true cross-tolerance to CPT."	( Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration. Antoniou, K; Ferré, S; Fuxe, K; Goldberg, SR; Justinova, Z; Karcz-Kubicha, M; Müller, CE; Pezzola, A; Popoli, P; Quarta, D; Reggio, R; Solinas, M; Terasmaa, A, 2003)	0.78
" The present study was designed to determine the extent to which D2/3 receptor activation and blockade can modulate morphine-induced locomotion using a novel cumulative dosing procedure in Swiss-Webster mice."	( The modulatory actions of dopamine D2/3 agonists and antagonists on the locomotor-activating effects of morphine and caffeine in mice. Beardsley, PM; Cook, CD, 2003)	0.53
" Caffeine dosing in the PM (trial D 22."	( Effect of repeated caffeine ingestion on repeated exhaustive exercise endurance. Bell, DG; McLellan, TM, 2003)	1.56
"Prescribed at a dosage close to twice the recommendations of the literature, monohydrated caffeine does not provide efficient plasma rates."	( [Pharmacologic study of monohydrated caffeine in the treatment of apnoea of premature infant]. Belkahia, C; Boukef-Larguèche, S; Chaouachi, S; Cherif, A; Klouz, A; Marrakchi, Z, 2003)	0.81
"To compare the effectiveness of three dosing regimens of caffeine for preterm infants in the periextubation period."	( Periextubation caffeine in preterm neonates: a randomized dose response trial. Charles, BG; Flenady, VJ; Lee, TC; Shearman, A; Steer, PA; Tudehope, DI, )	0.73
"A randomized double-blind clinical trial of three dosing regimens of caffeine citrate (3, 15 and 30 mg/kg) for periextubation management of ventilated preterm infants was undertaken."	( Periextubation caffeine in preterm neonates: a randomized dose response trial. Charles, BG; Flenady, VJ; Lee, TC; Shearman, A; Steer, PA; Tudehope, DI, )	0.72
" No statistically significant difference was demonstrated in the incidence of extubation failure between dosing groups (19, 10, and 11 infants in the 3, 15, and 30 mg/kg groups, respectively), however, infants in the two higher dose groups had statistically significantly less documented apnoea than the lowest dose group."	( Periextubation caffeine in preterm neonates: a randomized dose response trial. Charles, BG; Flenady, VJ; Lee, TC; Shearman, A; Steer, PA; Tudehope, DI, )	0.48
" Further studies with larger numbers of infants assessing longer-term outcomes are necessary to determine the optimal dosing regimen of caffeine in preterm infants."	( Periextubation caffeine in preterm neonates: a randomized dose response trial. Charles, BG; Flenady, VJ; Lee, TC; Shearman, A; Steer, PA; Tudehope, DI, )	0.69
" After responding stabilized, dose-response curves were determined for other drugs."	( Retention of sequential drug discriminations under fixed-interval schedules for long time periods without training. Li, M; McMillan, DE, 2003)	0.32
" The effect is observable with both stationary-phase and log-phase populations, but is not observable when a relatively high dosage of ultraviolet light is employed."	( "Mutational synergism" of ultraviolet light and caffeine in Escherichia coli. SHANKEL, DM, 1962)	0.5
"8% at a dosage of 5 micromol/L caffeine."	( The effect of caffeine on peripheral vascular resistance in isolated perfused guinea pig hind limbs. Brodmann, M; Lischnig, U; Lueger, A; Pilger, E; Stark, G, 2003)	0.97
" To evaluate the sensitivity of the Finometer in recording longer-term effects of a daily dosage of 1000 mg vitamin C, 800 mg vitamin E and 10 mg folic acid, 14 young males took placebo and 17 took the vitamins for 12 weeks in a double-blind study."	( Sensitivity of the Finometer device in detecting acute and medium-term changes in cardiovascular function. Huisman, HW; Jerling, JC; Oosthuizen, W; Schutte, AE; Van Rooyen, JM, 2003)	0.32
" Remarkably, the effective dosage varies widely among patients, making it necessary to individualize drug therapy with clozapine."	( CYP1A2 activity is an important determinant of clozapine dosage in schizophrenic patients. Doude van Troostwijk, LJ; Guchelaar, HJ; Koopmans, RP; Vermeulen, HD, 2003)	0.32
"Maximal QTc interval and SBP assessed at 1, 3, and 5 hours after dosing for the DSEC relative to placebo."	( Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial. Coleman, CI; Karapanos, AK; Kluger, J; Krudysz, A; McBride, BF; White, CM, 2004)	0.54
" There was no difference in blood pressure and blood glucose concentrations following the cocktail and dosing of the individual probes."	( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1. Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004)	0.32
"The five probe drugs when coadministered, in this dosing regimen, demonstrated no evidence of either a metabolic or pharmacodynamic interaction that might confound the conclusions drawn during a cocktail study."	( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1. Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004)	0.32
" The RP-HPLC method was done for the determination of paracetamol, caffeine and propyphenazone in a multicomponent pharmaceutical dosage form."	( Optimization of the RP-HPLC method for multicomponent analgetic drug determination. Ivanovic, D; Jancic, B; Malenovic, A; Medenica, M; Misljenovic, Dj, 2003)	0.56
" These data indicate that the involvement of ATM following treatment with Topo poisons differs extensively with dosage and for different cell cycle checkpoints."	( Topoisomerase poisons differentially activate DNA damage checkpoints through ataxia-telangiectasia mutated-dependent and -independent mechanisms. Arooz, T; Chow, JP; Ho, HT; Lau, A; Poon, RY; Siu, WY, 2004)	0.32
" The results support the conclusion that caffeine ingestion has a dose-response effect on reducing leg muscle pain during exercise and that these effects do not depend on caffeine-induced increases in systolic blood pressure during exercise."	( Dose-dependent effect of caffeine on reducing leg muscle pain during cycling exercise is unrelated to systolic blood pressure. Broglio, SP; Ely, MR; Motl, RW; O'Connor, PJ, 2004)	0.89
" A marked (2 patients) or a moderate (2 patients) improvement of the clinical state of the patients occurred after the increase of CLO blood levels above the therapeutic threshold by the increase of CLO doses to very high values (ie, up to 1400 mg/d) or by the introduction of fluvoxamine, a potent CYP1A2 inhibitor, at low dosage (50 to 100 mg/d)."	( Nonresponse to clozapine and ultrarapid CYP1A2 activity: clinical data and analysis of CYP1A2 gene. Allorge, D; Baumann, P; Bender, S; Broly, F; Cucchia, G; Eap, CB; Jaquenoud Sirot, E; Jonzier-Perey, M, 2004)	0.32
" Caffeine shifted the GABA dose-response curve downward and decreased the maximum response to 57% without changing K(d) value."	( [Inhibitory effect of caffeine on GABA-activated current in acutely isolated rat dorsal root ganglion neurons]. An, J; Li, S; Li, ZW; Sun, CK, 2004)	1.55
"Compared with the conventional delivery systems, drug release from the new dosage form may offer a new dimension for the oral treatment of mid to distal ulcerative colitis."	( In vivo evaluation of a novel pH- and time-based multiunit colonic drug delivery system. Bott, C; Dressman, JB; Langguth, P; Petereit, HU; Rudolph, MW; Schirrmacher, S; Schneider, AR; Skalsky, B; Stein, J, 2004)	0.32
" Our objective was to determine the time course of CYP1A2 activity changes after smoking cessation in heavy smokers as the basis for dosing adaptation schemes."	( Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. Faber, MS; Fuhr, U, 2004)	0.32
" A caffeine dosage of 7 mg."	( Physiologic effects of caffeine on cross-country runners. Birnbaum, LJ; Herbst, JD, 2004)	1.26
"5 microM) shifted the dose-response curve of ryanodine- or caffeine-induced 45Ca2+ release from the vesicles to the left."	( Elucidation of the ryanodine-sensitive Ca2+ release mechanism of rat pancreatic acinar cells: modulation by cyclic ADP-ribose and FK506. Ozawa, T, 2004)	0.57
" In phase I (30 experiments on 8 dogs), the doses were established by dose-response curve."	( Effects of cocaine and caffeine alone and in combination on cardiovascular performance: an experimental hemodynamic and coronary flow reserve study in a canine model. Billie, M; Jain, AC; Mehta, MC, 2004)	0.63
"Powder filled sachets containing a 3:1 (w/w) powder mixture of diacetylmorphine base and caffeine anhydrate were developed as a dosage form for smokable heroin used for the treatment of chronic, treatment-resistant heroin addicts."	( Process characterisation, optimisation and validation of production of diacetylmorphine/caffeine sachets: a design of experiments approach. Beijnen, JH; Klous, MG; Nuijen, B; Van den Brink, W; Van Ree, JM, 2004)	0.77
" A pharmaceutical dosage form for inhalable heroin was developed for this trial, consisting of a 3:1 powder mixture of diacetylmorphine base and caffeine anhydrate."	( Development and manufacture of diacetylmorphine/caffeine sachets for inhalation via 'chasing the dragon' by heroin addicts. Beijnen, JH; Klous, MG; Nuijen, B; van den Brink, W; van Ree, JM, 2004)	0.78
"To compare two dosing regimens for caffeine citrate in the periextubation period for neonates born at less than 30 weeks gestation in terms of successful extubation and adverse effects."	( High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial. Bury, G; Charles, B; Charlton, M; Flenady, V; Fraser, S; Gray, PH; Hegarty, J; Henderson-Smart, D; Horton, L; Jacklin, R; Reid, S; Rogers, Y; Shearman, A; Steer, P; Walsh, A, 2004)	1
"Two dosing regimens of caffeine citrate (20 v 5 mg/kg/day) for periextubation management."	( High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial. Bury, G; Charles, B; Charlton, M; Flenady, V; Fraser, S; Gray, PH; Hegarty, J; Henderson-Smart, D; Horton, L; Jacklin, R; Reid, S; Rogers, Y; Shearman, A; Steer, P; Walsh, A, 2004)	1.04
" A significant reduction in failure to extubate was shown for the 20 mg/kg/day dosing group (15."	( High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial. Bury, G; Charles, B; Charlton, M; Flenady, V; Fraser, S; Gray, PH; Hegarty, J; Henderson-Smart, D; Horton, L; Jacklin, R; Reid, S; Rogers, Y; Shearman, A; Steer, P; Walsh, A, 2004)	0.73
"This trial shows short term benefits for a 20 mg/kg/day dosing regimen of caffeine citrate for neonates born at less than 30 weeks gestation in the periextubation period, without evidence of harm in the first year of life."	( High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial. Bury, G; Charles, B; Charlton, M; Flenady, V; Fraser, S; Gray, PH; Hegarty, J; Henderson-Smart, D; Horton, L; Jacklin, R; Reid, S; Rogers, Y; Shearman, A; Steer, P; Walsh, A, 2004)	0.96
" Its transnasal dosage form, which may be self-administered when the use of an opioid analgesic is appropriate, was previously shown to provide rapid relief of migraine pain."	( Comparison of butorphanol nasal spray and fiorinal with codeine in the treatment of migraine. Davidson, WJ; Diamond, S; Gawel, MJ; Goldstein, J; Reich, L; Sussman, NM; Winner, P, )	0.13
" The direction of dosing adjustments during pregnancy will depend on the drug and the enzyme that is responsible for its metabolism."	( Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy. Caritis, SN; Glover, DD; Tracy, TS; Venkataramanan, R, 2005)	0.33
"The aim of research was to design a small, restraint free, low stress animal dosing chamber for inhalation studies, and to investigate distribution of a model drug within the chamber."	( Design and evaluation of a restraint-free small animal inhalation dosing chamber. Burgess, D; Carvalho, TC; Iberg, AN; Johnston, KP; McConville, JT; Peters, JI; Talbert, RL; Williams, RO, 2005)	0.33
"Caffeine exerts mild deleterious dose-response effects on recovery sleep following total sleep deprivation, primarily early in the sleep period, with potential recovery from these effects after sufficient sleep as suggested by lack of post-recovery sleep performance deficits."	( Caffeine effects on recovery sleep following 27 h total sleep deprivation. Balkin, TJ; Belenky, G; Kamimori, GH; LaJambe, CM, 2005)	3.21
"Riluzole is used in a fixed dosing schedule of 50 mg twice daily to treat patients with amyotropic lateral sclerosis (ALS), one form of motor neurone disease."	( Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis. Groeneveld, GJ; Guchelaar, HJ; Kalmijn, S; Spieksma, M; van den Berg, LH; van Kan, HJ, 2005)	0.33
" Dosage suppression analysis identified different groups of genes in rescuing phenotypes of different tsc11(ts) mutants."	( Saccharomyces cerevisiaeTSC11/AVO3 participates in regulating cell integrity and functionally interacts with components of the Tor2 complex. Chen, MY; Ho, HL; Shiau, YS, 2005)	0.33
" Stimulus-generalization curves were generated by cumulative dosing for d-amphetamine (0."	( Caffeine induces differential cross tolerance to the amphetamine-like discriminative stimulus effects of dopaminergic agonists. Holtzman, SG; Jain, R, 2005)	1.77
" The diabetes risk was negatively related to the consumption in a dose-response manner."	( Coffee, tea and diabetes: the role of weight loss and caffeine. Axen, KV; Boozer, CN; Greenberg, JA; Schnoll, R, 2005)	0.58
" We sought to determine whether repeated dosing and multi-ingredient formulations contribute to the adverse effects of these supplements."	( Short-term metabolic and hemodynamic effects of ephedra and guarana combinations. Benowitz, NL; Haller, CA; Jacob, P, 2005)	0.33
" The results of the proposed method were in excellent agreement with those obtained from PLS and HPLC methods and can be satisfactorily used for routine analysis of multicomponent dosage forms."	( Content uniformity and dissolution tests of triplicate mixtures by a double divisor-ratio spectra derivative method. Koundourellis, JE; Malliou, ET; Markopoulou, CK, 2005)	0.33
" Caffeine alone did not change RBF, but shifted the dose-response curve of adenosine to the right during concomitant infusion of caffeine."	( Mechanisms of adenosine-induced renal vasodilatation in hypertensive patients. de Leeuw, PW; Houben, AJ; Koster, D; Kroon, AA; Postma, CT; Smits, P; van Engelshoven, JM; Wierema, TK, 2005)	1.24
"A ratio-spectra zero-crossing first-derivative spectrophotometric method and 2 chemometric methods have been used for the simultaneous determination of ternary mixtures of caffeine (A), 8-chlorotheophylline (B), and chlorphenoxamine hydrochloride (C) in bulk powder and dosage forms."	( Simultaneous determination of caffeine, 8-chlorotheophylline, and chlorphenoxamine hydrochloride in ternary mixtures by ratio-spectra zero-crossing first-derivative spectrophotometric and chemometric methods. Kelani, KM, )	0.61
"The results suggest that caffeine administered in the gum formulation (Stay Alert chewing gum) via a multiple dosing regimen provides an effective and convenient means of maintaining effective concentrations of caffeine that would in some operational scenarios be desirable for maintaining alertness and performance in sleep deprived individuals."	( Multiple dose pharmacokinetics of caffeine administered in chewing gum to normal healthy volunteers. Eddington, ND; Kamimori, GH; Kelly, W; Syed, SA, 2005)	0.91
" Caffeine dosage was based on patient weight (equivalent to a 70 kg person taking 200 mg of caffeine twice a day)."	( Caffeine ingestion and lower urinary tract symptoms in healthy volunteers. Bird, ET; Coffield, KS; Kim, HS; Parker, BD, 2005)	2.68
" Dopamine-deficient mice have a rightward shift in the dose-response curve to morphine on the tail-flick test (a pain sensitivity assay), suggesting either a decreased sensitivity to the analgesic effects of morphine and/or basal hyperalgesia."	( Morphine reward in dopamine-deficient mice. Hnasko, TS; Palmiter, RD; Sotak, BN, 2005)	0.33
" Reproducible shifts in the dose-response of skeletal muscle to caffeine and halothane are the basis of the current in vitro diagnostic caffeine-halothane contracture test."	( Effects of caffeine, halothane, and 4-chloro-m-cresol on skeletal muscle lactate and pyruvate in malignant hyperthermia-susceptible and normal swine as assessed by microdialysis. Bina, S; Bünger, R; Cowan, G; Karaian, J; Mongan, P; Muldoon, S, 2006)	0.96
" MH susceptibility leads to a leftward shift of the dose-response curve for IM lactate after local injection of halothane and caffeine."	( The dose-response relationship and regional distribution of lactate after intramuscular injection of halothane and caffeine in malignant hyperthermia-susceptible pigs. Anetseder, M; Hager, M; Müller, R; Roewer, N; Schöll, H; Schuster, F, 2006)	0.75
" The purpose of the current study was to identify changes in caffeine pharmacokinetics, resting energy expenditure (REE), oxygen consumption (VO(2)) and respiratory exchange ratio (RER) after an acute dosage of caffeine and naringin."	( Naringin does not alter caffeine pharmacokinetics, energy expenditure, or cardiovascular haemodynamics in humans following caffeine consumption. Agrawal, P; Ballard, TL; Halaweish, FT; Stevermer, CL; Vukovich, MD, 2006)	0.88
"In preparation for a trial on co-prescription of heroin to chronic treatment-resistant addicts, a pharmaceutical dosage form for smokable heroin was developed."	( Volatilisation of diacetylmorphine: in vitro simulation of 'chasing the dragon'. Beijnen, JH; Klous, MG; Lee, WC; Van den Brink, W; Van Ree, JM, 2006)	0.33
" The antinociceptive efficacies were evaluated using several dose-response curves and time courses."	( Enhancement of antinociception by co-administration of ibuprofen and caffeine in arthritic rats. Bravo, G; Cook, HJ; Déciga-Campos, M; Díaz-Reval, MI; Domínguez-Ramírez, AM; López, JR; López-Muñoz, FJ, 2006)	0.57
"The extraction methods in selected monographs of the European and the Swiss Pharmacopoeia were compared to pressurized liquid extraction (PLE) with respect to the yield of constituents to be dosed in the quantitative assay for the respective herbal drugs."	( Are extraction methods in quantitative assays of pharmacopoeia monographs exhaustive? A comparison with pressurized liquid extraction. Basalo, C; Hamburger, M; Mohn, T, 2006)	0.33
" However, it provides a valuable aid to decision-making with regard to first-time dosing in children and study design."	( Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Johnson, TN; Rostami-Hodjegan, A; Tucker, GT, 2006)	0.33
" After 5 days dosing of GPi819 (37."	( Sensitivity of glycogen phosphorylase isoforms to indole site inhibitors is markedly dependent on the activation state of the enzyme. Allen, JM; Bartlett, JB; Charles, AD; Convey, G; Freeman, S; Hardern, I; Loxham, SJ; Poucher, SM; Teague, JL, 2006)	0.33
" The recommended dosing for caffeine is a loading dose of 20 mg/kg followed by a 5 mg/kg/d maintenance dose."	( Serum caffeine concentrations in preterm neonates. Hutchison, AA; Leon, AE; Ma, CX; Michienzi, K, 2007)	1.11
" Here, we aimed to investigate the effect of caffeine consumption on the methotrexate dosing requirements in patients with psoriasis and psoriatic arthritis."	( Caffeine consumption and methotrexate dosing requirement in psoriasis and psoriatic arthritis. Barnes, SA; el-Azhary, RA; Mengden Koon, SJ; Swanson, DL, 2007)	2.04
"One hundred and fifty patients with diagnoses of psoriasis or psoriatic arthritis were surveyed for their current weekly methotrexate dosage and their usual daily consumption of caffeine."	( Caffeine consumption and methotrexate dosing requirement in psoriasis and psoriatic arthritis. Barnes, SA; el-Azhary, RA; Mengden Koon, SJ; Swanson, DL, 2007)	1.97
"Seventy-five of the patients given the survey responded; of these, 11 were eliminated because they did not report their methotrexate dosage or were no longer taking methotrexate."	( Caffeine consumption and methotrexate dosing requirement in psoriasis and psoriatic arthritis. Barnes, SA; el-Azhary, RA; Mengden Koon, SJ; Swanson, DL, 2007)	1.78
"Our findings suggest that caffeine does not affect methotrexate dosage requirements in patients with psoriasis and psoriatic arthritis."	( Caffeine consumption and methotrexate dosing requirement in psoriasis and psoriatic arthritis. Barnes, SA; el-Azhary, RA; Mengden Koon, SJ; Swanson, DL, 2007)	2.08
"Our results indicate that TJ-19 at the generally recommended dosage is unlikely to cause pharmacokinetic interaction with co-administered medications primarily dependent on the CYP1A2, CYP2D6, CYP3A, XO, and NAT2 pathways for elimination."	( The effect of Shoseiryuto, a traditional Japanese medicine, on cytochrome P450s, N-acetyltransferase 2 and xanthine oxidase, in extensive or intermediate metabolizers of CYP2D6. Fukushima, Y; Hisadome, M; Muramoto, Y; Nakagawa, K; Nakao, M; Saruwatari, J; Shoji, M; Yamano, N, 2007)	0.34
" In addition, for compounds with differences in regional absorption within the gastrointestinal tract a dosage form with a bi-modal release profile may be required, which is difficult to achieve with a simple dosage form."	( Modulation of drug release kinetics from hydroxypropyl methyl cellulose matrix tablets using polyvinyl pyrrolidone. Booth, SW; Byway, PV; Fitzpatrick, S; Hardy, IJ; Neri, C; Windberg-Baarup, A, 2007)	0.34
" The purpose of this study was to determine the effect of 2 levels of caffeine dosage on the metabolic and cardiorespiratory responses to treadmill walking in women."	( The physiological effects of caffeine in women during treadmill walking. Ahrens, JN; Crixell, SH; Lloyd, LK; Walker, JL, 2007)	0.86
" The proposed method is rapid and sensitive and, therefore, suitable for the routine control of these ingredients in multicomponent dosage forms."	( Determination of the analgesic components of Spasmomigraine tablet by liquid chromatography with ultraviolet detection. El-Dawy, MA; Elbarbry, FA; Mabrouk, MM, )	0.13
" For caffeine and scopolamine, even the lowest dosage tested (5 mg/horse/day and 2 mg/horse/day respectively) induced detectable concentrations of the molecule in urine."	( Urinary excretion of dietary contaminants in horses. Bonnaire, Y; Julliand, V; Lallemand, A; Respondek, F, 2006)	0.85
" Increasing dosage (trend P = ."	( Smoking, caffeine, and nonsteroidal anti-inflammatory drugs in families with Parkinson disease. Hancock, DB; Jewett, R; Martin, ER; Scott, BL; Scott, WK; Stacy, MA; Stajich, JM; Vance, JM, 2007)	0.76
" Depending on the intended indication and dosing regimen, PPL can delay or stop development of a compound in the drug discovery process."	( Evaluation of a published in silico model and construction of a novel Bayesian model for predicting phospholipidosis inducing potential. Gehlhaar, D; Greene, N; Johnson, TO; Pelletier, DJ; Tilloy-Ellul, A, )	0.13
" To analyze a possible interaction between both drugs a dose-response curve to ASA plus a fixed dose of CAF (5mg/kg) was obtained 3h after the injection of carrageenan, when the inflammatory pain peaked."	( Adjuvant effect of caffeine on acetylsalicylic acid anti-nociception: prostaglandin E2 synthesis determination in carrageenan-induced peripheral inflammation in rat. Fernández-Dueñas, V; Planas, E; Poveda, R; Sánchez, S, 2008)	0.67
" Following this repeated caffeine doses were administered to test the claim that repeated dosing has no extra effect on mood or performance."	( Effects of repeated doses of caffeine on performance and alertness: new data and secondary analyses. Hewlett, P; Smith, A, 2007)	0.93
" To distinguish between blocking and suppressing effects, and thus provide mechanistic insights into prevention during the initiation versus post-initiation phases of carcinogenesis, white tea, and green tea were administered at 2% (w/v) as the sole source of drinking fluid either 2 wk before and 2 wk during PhIP dosing (100 mg/kg, every other day by oral gavage), or starting 1 wk after the carcinogen and continued until the study was terminated at 16 wk."	( Comparison of white tea, green tea, epigallocatechin-3-gallate, and caffeine as inhibitors of PhIP-induced colonic aberrant crypts. Bailey, GS; Carter, O; Dashwood, RH; Dashwood, WM; Fischer, KA; Löhr, CV; Orner, GA; Pereira, CB; Wang, R; Williams, DE, 2007)	0.58
" Present paper introduces the development and validation of analytical methods suitable for quantitative determination of paracetamol containing dosage forms in FoNo VII."	( [Current problems in the quality control of pharmaceutical preparations manufactured in pharmacies II. Paracetamol contraining preparations]. Horváth, P; Sinkó, B; Takaćsne, NK; Völgyi, G, 2006)	0.33
"In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks."	( Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, mu Cerbo, R; Del Bene, E; Ferrari, A; Genco, S; Grazioli, I; Martelletti, P; Nappi, G; Pinessi, L; Sandrini, G; Sarchielli, P; Tamburro, P; Uslenghi, C; Zanchin, G, 2007)	0.75
"The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf."	( Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, mu Cerbo, R; Del Bene, E; Ferrari, A; Genco, S; Grazioli, I; Martelletti, P; Nappi, G; Pinessi, L; Sandrini, G; Sarchielli, P; Tamburro, P; Uslenghi, C; Zanchin, G, 2007)	0.55
" The methods used at NIST to determine the concentration levels of caffeine, theobromine, and theophylline in SRM 3243 Ephedra-Containing Solid Oral Dosage Form and SRM 3244 Ephedra-Containing Protein Powder used reversed-phase liquid chromatography with absorbance detection and tandem mass spectrometry."	( Determination of caffeine and caffeine-related metabolites in ephedra-containing standard reference materials using liquid chromatography with absorbance detection and tandem mass spectrometry. Mitvalsky, S; Roman, M; Satterfield, MB; Sharpless, KE; Thomas, JB; Yen, J, )	0.71
" Conversely, upon smoking cessation, smokers may require a reduction in the dosage of an interacting medication."	( Drug interactions with smoking. Kroon, LA, 2007)	0.34
" As disintegration time is shortest at a certain ratio of disintegrant, a calculation of this value is important for solid dosage from design to enhance disintegration and dissolution process."	( Rational estimation of the optimum amount of non-fibrous disintegrant applying percolation theory for binary fast disintegrating formulation. Betz, G; Krausbauer, E; Leuenberger, H; Puchkov, M, 2008)	0.35
" Mean MDMA dosage of tablets decreased from 1999 to 2003 and dosage for tablets bearing the same logo appeared to be highly variable."	( Monitoring ecstasy content in France: results from the National Surveillance System 1999-2004. Bello, PY; Giraudon, I, 2007)	0.34
" Although it has been suggested that decrements in cognitive performance are present in the range of a 2 to 3% reduction in body weight, several dose-response studies indicate dehydration levels of 1% may adversely affect cognitive performance."	( Hydration and cognition: a critical review and recommendations for future research. Lieberman, HR, 2007)	0.34
" Careful dosing of tizanidine is warranted in small females, whereas male smokers can require higher than average doses."	( Effects of gender and moderate smoking on the pharmacokinetics and effects of the CYP1A2 substrate tizanidine. Backman, JT; Neuvonen, PJ; Schröder, MT, 2008)	0.35
" However, it is unknown to what extent such deficits are exacerbated in a dose-response manner by increasing levels of sleepiness, and the extent to which such sleep-loss-induced deficits can be reversed by caffeine."	( Caffeine effects on risky decision making after 75 hours of sleep deprivation. Balkin, TJ; Kamimori, GH; Killgore, WD; Lipizzi, EL, 2007)	1.97
" Most studies confirm a protective effect against type 2 diabetes, with some dose-response in function of the degree of daily coffee consumption."	( [Does coffee protect against type 2 diabetes?]. Legrand, D; Scheen, AJ, 2007)	0.34
" Seven healthy volunteers were dosed with carbamazepine over 16 consecutive days."	( Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin. Cederberg, J; Dahl, ML; Karlsson, MO; Magnusson, MO; Sandström, R, 2008)	0.55
" Smoking and coffee exhibited significant inverse risk trends with increasing cumulative exposures, suggesting dose-response relations."	( Combined effects of smoking, coffee, and NSAIDs on Parkinson's disease risk. Checkoway, H; Factor, SA; Griffith, A; Higgins, DS; Kay, DM; Leis, B; Martinez, ED; Montimurro, JS; Nutt, JG; Payami, H; Powers, KM; Roberts, JW; Samii, A; Zabetian, CP, 2008)	0.35
" Dosage adjustments may be required for drugs that are substrates of CYP3A4 (e."	( Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects. Darwish, M; Hellriegel, ET; Kirby, M; Robertson, P, 2008)	0.35
" Unfortunately, research subsequent to our study design has shown that D-ribose dosing higher than we used is needed to see a clinical effect and therefore no conclusions can be made from this study as to the efficacy of D-ribose."	( Effects of oral administration of caffeine and D-ribose on mental fatigue. Ataka, S; Kajimoto, O; Kajimoto, Y; Kuratsune, H; Mizuma, H; Mizuno, K; Nozaki, S; Shirai, T; Sugino, T; Tahara, T; Tanaka, M; Watanabe, Y, 2008)	0.63
"3-fold larger than from the emulsion and gel dosage forms."	( Percutaneous release of caffeine from microemulsion, emulsion and gel dosage forms. Bolzinger, MA; Briançon, S; Chevalier, Y; Fessi, H; Pelletier, J, 2008)	0.65
" A caffeine-loading test was conducted at a dosage of 4 mg per body weight (kg)."	( Lack of association of the Trp64Arg polymorphism of beta3-adrenergic receptor gene with energy expenditure in response to caffeine among young healthy women. Hamada, T; Higashi, A; Igarashi, A; Ikeda, J; Kotani, K; Matsubara, C; Sakane, N; Tagaki, E; Yoshida, T, 2008)	1.17
" The purpose of this project was to determine whether a moderate dosage of caffeine, a common ventilatory stimulant, could augment resting ventilatory responsiveness, exercise ventilation (V E), end-tidal O2 partial pressure (PetO2), and arterial oxyhemoglobin saturation (HbSaO2) in athletes with EIH."	( Caffeine stimulates ventilation in athletes with exercise-induced hypoxemia. Chapman, RF; Stager, JM, 2008)	2.02
" Salicylic acid, caffeine and metoprolol were individually dosed to the ligated stomach."	( The development of multiple probe microdialysis sampling in the stomach. Lunte, CE; Woo, KL, 2008)	0.69
" To assess the significance of this multiple probe approach, drug concentrations in each probe location were monitored after selected compounds were dosed to the ligated stomach by oral gavage."	( The direct comparison of health and ulcerated stomach tissue: a multiple probe microdialysis sampling approach. Lunte, CE; Woo, KL, 2008)	0.35
" In rats administered CDDP-L, it was discovered that the antitumor effect was not only enhanced by the coadministration of caffeine but also further enhanced when the dosing period of caffeine was increased."	( The antitumor effect of liposome-encapsulated cisplatin on rat osteosarcoma and its enhancement by caffeine. Karita, M; Kasaoka, S; Kawahara, M; Tomita, K; Tsuchiya, H, )	0.56
" When three different dosing schedules of caffeine were given, the extent of tumor inhibition was closely correlated with the average plasma concentration of caffeine."	( Caffeine dose-dependently potentiates the antitumor effect of cisplatin on osteosarcomas. Kawahara, M; Miyamoto, K; Takahashi, Y; Takazawa, K; Tomita, K; Tsuchiya, H; Yokogawa, K, )	1.84
" Electrophysiological results did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in the combined treatment, similar to previous findings at a larger dosage of L-theanine alone."	( L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance. Foxe, JJ; Gomez-Ramirez, M; Kelly, SP; Montesi, JL, 2008)	0.7
"Caffeine, CPT, and MSX-3 partially generalized to nicotine and shifted nicotine dose-response curves leftwards."	( Effects of chronic caffeine exposure on adenosinergic modulation of the discriminative-stimulus effects of nicotine, methamphetamine, and cocaine in rats. Barnes, C; Ferré, S; Goldberg, SR; Justinova, Z; Le Foll, B; Pappas, LA; Wertheim, CE, 2009)	2.12
" In study A, 1,000 mg mesalazine doses were given thrice daily for 5 days, and urine and blood samples were drawn during the last dosing interval."	( Mesalazine pharmacokinetics and NAT2 phenotype. Fuhr, U; Jetter, A; Kinzig, M; Lück, H; Sörgel, F, 2009)	0.35
"The skin absorption from Pickering emulsions as a new dosage form was investigated for the first time."	( Pickering w/o emulsions: drug release and topical delivery. Bolzinger, MA; Chevalier, Y; Frelichowska, J; Mouaziz, H; Pelletier, J; Valour, JP, 2009)	0.35
" Infants of gestational age <30 weeks were randomly allocated to receive maintenance caffeine citrate dosing of either 5 or 20 mg/kg/d."	( Caffeine citrate treatment for extremely premature infants with apnea: population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring. Charles, BG; Flenady, VJ; Gray, PH; Shearman, A; Steer, PA; Townsend, SR, 2008)	2.01
"Any sampling interval at least 4 h after caffeine dosing is suitable for NAT2 and XO activity assessments."	( Phenotyping of N-acetyltransferase type 2 and xanthine oxidase with caffeine: when should urine samples be collected? Fuhr, U; Jetter, A; Kinzig, M; Rodamer, M; Sörgel, F; Tomalik-Scharte, D, 2009)	0.85
" The final pharmacostatistical model was then subjected to stochastic simulation to predict the plasma concentrations of caffeine after oral (204, 340 and 476 mg) dosing regimens (repeated dosing every 6, 8 or 12 h) over a hypothetical 3-day period."	( Population pharmacokinetics of caffeine in healthy male adults using mixed-effects models. Fan, W; Fun, CY; Law, YL; Lim, CL; Lim, WM; Seng, KY, 2009)	0.85
" Dosing simulations indicated that dosing regimens of 340 mg (repeated every 8 h) and 476 mg (repeated every 6 h) should achieve population-averaged caffeine concentrations within the reported beneficial range (4."	( Population pharmacokinetics of caffeine in healthy male adults using mixed-effects models. Fan, W; Fun, CY; Law, YL; Lim, CL; Lim, WM; Seng, KY, 2009)	0.84
" Therefore, patients taking caffeine-containing medicine or coffee drinkers taking drugs that interact with CYP1A2 may require proper dosage adjustments upon caffeine ingestion and cessation."	( Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat. Daniel, WA; Kot, M, )	1.87
" We investigate if this nonlinear dose-response is present for caffeine's effects on functional activation."	( Caffeine dose effect on activation-induced BOLD and CBF responses. Chen, Y; Parrish, TB, 2009)	2.04
" Following recovery, animals were dosed with caffeine (10 mg/kg) alone or in combination with zolpidem (10 mg/kg) or trazodone (20 mg/kg)."	( Characterisation of the effects of caffeine on sleep in the rat: a potential model of sleep disruption. Hutson, PH; Ivarsson, M; Nutt, DJ; Paterson, LM; Wilson, SJ, 2009)	0.89
" In the high-dose male GTC-H group, a lower total motor activity count for the 60-min session was noted prior to dosing at the study week 25 evaluations compared to the control group."	( Safety assessment of heat-sterilized green tea catechin preparation: a 6-month repeat-dose study in rats. Beck, MJ; Bruner, RH; Chengelis, CP; Kirkpatrick, JB; Morita, O; Tamaki, Y, 2009)	0.35
" We conclude firstly that propofol is safe for individuals with predisposition to malignant hyperthermia when it is used within the recommended clinical dosage range, and secondly that its mode of action upon ryanodine receptors is likely to be different from that of caffeine."	( Effects of propofol on calcium homeostasis in human skeletal muscle. Hamada, H; Kawamoto, M; Kobayashi, M; Migita, T; Mukaida, K; Nishino, I; Yuge, O, 2009)	0.53
" The glycine dose-response curves and the effects of caffeine indicate that amphibian retinal ganglion cells do not express a plethora of GlyR subtypes and are dominated by the alpha1beta GlyR."	( Caffeine inhibition of ionotropic glycine receptors. Duan, L; Slaughter, MM; Yang, J, 2009)	2.05
" Caffeine improved alerting and executive control function in a dose-response manner, asymptoting at 200mg; this effect is congruent with caffeine's adenosine-mediated effects on dopamine-rich areas of brain, and the involvement of these areas in alerting and the executive control of visual attention."	( Caffeine modulates attention network function. Brunyé, TT; Lieberman, HR; Mahoney, CR; Taylor, HA, 2010)	2.71
" Treatment was successful with prednisone, started at a dosage of 1 mg/kg/d, for 5 months."	( A case of linear immunoglobulin A bullous dermatosis in a patient exposed to sun and an analgesic. Caldarola, G; Cozzani, E; Parodi, A; Pellicano, R, 2009)	0.35
"0001), with men experiencing greater dose-response than women."	( CYP1A2, GSTM1, and GSTT1 polymorphisms and diet effects on CYP1A2 activity in a crossover feeding trial. Chen, C; Eaton, DL; King, IB; Lampe, JW; Li, L; Li, SS; Peterson, S; Potter, JD; Schwarz, Y, 2009)	0.35
"To determine whether a dose-response relationship exists between caffeine and 2000-m rowing performance."	( Dose response of caffeine on 2000-m rowing performance. Coombes, JS; Jenkins, DG; Leveritt, MD; Skinner, TL; Taaffe, DR, 2010)	0.94
" Using the CREB-dependent reporter gene CRE-luciferase we show that stimulation of CREB activity by caffeine exhibits a bell-shaped dose-response curve."	( Caffeine modulates CREB-dependent gene expression in developing cortical neurons. Connolly, S; Kingsbury, TJ, 2010)	2.02
" Using a bivascular liver perfusion dose-response curves to adenosine of the HA were performed in the presence and the absence of pan-adenosine blocker (8-SPT), A1 blocker (caffeine) or nitric oxide synthase-blocker (l-NMMA) after preconstriction with an alpha1-agonist (methoxamine)."	( A distinct nitric oxide and adenosine A1 receptor dependent hepatic artery vasodilatatory response in the CCl-cirrhotic liver. Groszmann, RJ; Mehal, WZ; Ripoll, C; Zipprich, A, 2010)	0.55
" The subjects' psychomotor performance was evaluated before and at various times after dosing by a test battery consisting of oculomotor assessment (saccadic velocity) as well as the computerised Swedish Performance Evaluation System."	( Interrelations between plasma caffeine concentrations and neurobehavioural effects in healthy volunteers: model analysis using NONMEM. Fun, CY; Law, YL; Lim, CL; Seng, KY; Teo, WL, 2010)	0.65
" Information on the pain condition and number of patients studied, dosing regimen, study design and analgesic outcome measures (total pain relief scores) was extracted and dichotomous outcomes were obtained by calculating the number of patients in each treatment group who achieved at least 50% of the maximum total pain relief score."	( A risk-benefit assessment of paracetamol (acetaminophen) combined with caffeine. Day, R; Graham, G; Palmer, H; Williams, K, 2010)	0.59
" The exact dosage of caffeine, its form and rate, should be more precisely specified in further studies."	( [Traumatic brain injuries--effects of alcohol and caffeine on intracranial pressure and cerebral blood flow]. Bednár, M; Bláha, M; Tichý, M; Vajner, L; Vajnerová, O, 2009)	0.92
" Univariate and multivariate logistic regressions adjusting for age, gender, cigarette smoking, alcohol use, tea consumption and physical activity were conducted with dose-response analysis."	( Moderate coffee consumption reduces the risk of hepatocellular carcinoma in hepatitis B chronic carriers: a case-control study. Chan, HL; Ho, SC; Leung, WW; Mok, TS; Wong, V; Yeo, W, 2011)	0.37
"97) with a significant dose-response effect (χ²=5."	( Moderate coffee consumption reduces the risk of hepatocellular carcinoma in hepatitis B chronic carriers: a case-control study. Chan, HL; Ho, SC; Leung, WW; Mok, TS; Wong, V; Yeo, W, 2011)	0.37
" In Phase 2, the dose-response curve shifted to the left with the combination of tramadol and each dose of caffeine."	( Tramadol and caffeine produce synergistic interactions on antinociception measured in a formalin model. Carrillo-Munguía, N; Díaz-Reval, MI; González-Trujano, ME; Martínez-Casas, M, 2010)	0.94
" sinesis Extract and SRM 3256 Green Tea-containing Oral Dosage Form) are characterized for the content of caffeine and a series of catechin species (gallic acid, catechin, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate (EGCG))."	( Determination of catechins and caffeine in proposed green tea standard reference materials by liquid chromatography-particle beam/electron ionization mass spectrometry (LC-PB/EIMS). Castro, J; Chumanov, K; Marcus, RK; Pregibon, T, 2010)	0.86
" Monensin, salinomycin and maduramycin at the dosage of 120, 60, and 5 mg/kg were administered in feed for 14 days."	( Effects of ionophores on liver CYP1A and 3A in male broilers. Jiang, SX; Mo, F; Yu, ZG; Zhang, JR; Zhang, LL; Zhao, J, 2010)	0.36
" These findings suggest that caffeine at the dosage utilized (6 mg/kg body mass) is a, legal drug that provides an ergogenic benefit in 12 and 33°C."	( Effect of ambient temperature on caffeine ergogenicity during endurance exercise. Anderson, JM; Armstrong, LE; Casa, DJ; Ganio, MS; Johnson, EC; Klau, JF; Maresh, CM; Volek, JS, 2011)	0.94
" The benzodiazepines produced a hormetic (inverted U-shaped) dose-response profile, with intermediate doses producing anxiolysis and no effect at higher doses; clonazepam, a high-potency benzodiazepine agonist, produced a locomotor impairment at the highest dose."	( Pharmacological analysis of zebrafish (Danio rerio) scototaxis. da Silva, AW; Gouveia, A; Herculano, AM; Maximino, C, 2011)	0.37
"To compare two dosing regimens for caffeine citrate for neonates born less than 30 weeks gestation in terms of development, temperament and behaviour."	( Caffeine citrate for very preterm infants: Effects on development, temperament and behaviour. Charles, BG; Flenady, VJ; Gray, PH; Steer, PA, 2011)	2.09
" A total of 287 infants with apnoea of prematurity or in the peri-extubation period were randomised to receive one of two dosage regimens (20 vs."	( Caffeine citrate for very preterm infants: Effects on development, temperament and behaviour. Charles, BG; Flenady, VJ; Gray, PH; Steer, PA, 2011)	1.81
"Caffeine citrate with a dosage regimen of 20 mg/kg/day did not result in adverse outcomes for development, temperament and behaviour."	( Caffeine citrate for very preterm infants: Effects on development, temperament and behaviour. Charles, BG; Flenady, VJ; Gray, PH; Steer, PA, 2011)	3.25
"8 for total maternal dietary caffeine intake or specific types of caffeinated beverages and anotia/microtia, esophageal atresia, small intestinal atresia, and craniosynostosis; however, dose-response patterns were absent."	( Maternal caffeine intake and risk of selected birth defects in the National Birth Defects Prevention Study. Browne, ML; Druschel, CM; Feldkamp, ML; Hoyt, AT; Marshall, EG; Rasmussen, SA; Romitti, PA, 2011)	1.08
"Medicines are most often oral solid dosage forms made into tablets or capsules, and there is little room for individualized doses."	( Inkjet printing of drug substances and use of porous substrates-towards individualized dosing. Ihalainen, P; Kronberg, L; Määttänen, A; Meierjohann, A; Peltonen, J; Sandler, N; Viitala, T, 2011)	0.37
" Finally, the influence of moderators such as BMI and dosage on the results was examined as well."	( The effects of catechin rich teas and caffeine on energy expenditure and fat oxidation: a meta-analysis. Dulloo, AG; Hursel, R; Rumpler, W; Tappy, L; Tremblay, A; Viechtbauer, W; Westerterp-Plantenga, MS, 2011)	0.64
" The trial included 5475 patients treated with vasobral in dosage 2 ml (1 ml contains 1 mg of alpha-dihydroergocryptine and 10 mg of caffeine) twice a day during 2 months."	( [Preventive treatment of migraine with vasobral: a multicenter trial]. Azimova, IuE; Tabeeva, GR, 2010)	0.56
" A clear inverse dose-response relationship between total caffeine intake and PD risk was observed."	( Intake of Japanese and Chinese teas reduces risk of Parkinson's disease. Fukushima, W; Fukuyama, H; Hirota, Y; Kawamura, N; Kiyohara, C; Miki, T; Miyake, Y; Nagai, M; Oeda, T; Sakae, N; Sasaki, S; Tanaka, K; Tsuboi, Y; Yamada, T, 2011)	0.61
" Adolescent rats had a biphasic dose-response to caffeine comparable to that reported for adult rats."	( Acute and adaptive motor responses to caffeine in adolescent and adult rats. Huggler, AL; Rhoads, DE; Rhoads, LJ, 2011)	0.89
" For dose-response studies, LS-180 cells were treated with different concentrations of the selected drugs followed by P-gp protein and gene expressions analyses."	( Exposure of LS-180 cells to drugs of diverse physicochemical and therapeutic properties up-regulates P-glycoprotein expression and activity. Abuznait, AH; Kaddoumi, A; Patrick, SG, 2011)	0.37
"Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology."	( Genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) outperforms the tagging SNP rs1495741 and is equivalent to the conventional 7-SNP NAT2 genotype. Albers, P; Angeli-Greaves, M; Aslam, M; Bánfi, G; Barski, D; Blaszkewicz, M; Bolt, HM; Brenner, W; Dietrich, H; Ebbinghaus, R; Ekici, AB; Falkenstein, M; Frees, S; Gerullis, H; Golka, K; Guballa, C; Hassan Rizvi, SA; Hengstler, JG; Ickstadt, K; Klein, T; Kress, A; Lehmann, ML; Löhlein, D; Moormann, O; Niegisch, G; Otto, T; Ovsiannikov, D; Prager, HM; Reckwitz, T; Roemer, HC; Romics, I; Roth, G; Schöps, W; Schwender, H; Seidel, T; Selinski, S; Steffens, M; Thüroff, JW; Truss, MC; Weistenhöfer, W; Winterpacht, A; Zimmermann, A, 2011)	0.37
""Biorelevant" media for the fed stomach, including fat emulsions, are routinely used during in vitro testing of solid dosage forms."	( Drug release from HPMC matrices in milk and fat-rich emulsions. Barrett, DA; Hardy, IJ; Melia, CD; Nott, KP; Ward, R; Williams, HD, 2011)	0.37
" These studies suggest that there is a possibility that high dosage of caffeine can harm the unborn baby or new born babies, if the mothers use caffeine."	( Effect of caffeine, norfloxacin and nimesulide on heartbeat and VEGF expression of zebrafish larvae. Agoramoorthy, G; Chakraborty, C; Hsu, CH; Lin, CS; Wen, ZH, 2011)	1
" Because of the increasing worldwide incidence of obesity, there is a need for more information regarding the optimal dosing of drug therapy to be made available to prescribers."	( Application of a systems approach to the bottom-up assessment of pharmacokinetics in obese patients: expected variations in clearance. Aarabi, M; Allabi, AC; Almond, LM; Ghobadi, C; Jamei, M; Johnson, TN; Rostami-Hodjegan, A; Rowland-Yeo, K, 2011)	0.37
" Prediction of the effects of obesity on drug clearance, normalized by various body size scalars, is of potential value in the design of clinical studies during drug development and in the introduction of dosage adjustments that are likely to be needed in clinical practice."	( Application of a systems approach to the bottom-up assessment of pharmacokinetics in obese patients: expected variations in clearance. Aarabi, M; Allabi, AC; Almond, LM; Ghobadi, C; Jamei, M; Johnson, TN; Rostami-Hodjegan, A; Rowland-Yeo, K, 2011)	0.37
"2 µm after 10 mg daily dosing to steady-state."	( A clinical study to assess CYP1A2 and CYP3A4 induction by AZD7325, a selective GABA(A) receptor modulator - an in vitro and in vivo comparison. Desai, D; Grimm, SW; Lin, J; Ribadeneira, MD; Smith, MA; Sunzel, M; Zhou, D, 2012)	0.38
"The aim of this study was to develop a multiple-unit dosage system that released model drug into the colon, and also to evaluate the efficiency of the dosage form in human volunteers."	( The development and in vivo evaluation of a colon drug delivery system using human volunteers. Muselík, J; Štembírek, J; Vetchý, D; Zimová, L, 2012)	0.38
"The aims of this study were to evaluate the effects of caffeine supplementation on sprint cycling performance and to determine if there was a dose-response effect."	( Caffeine and sprinting performance: dose responses and efficacy. Foley, P; Glaister, M; McInnes, G; Patterson, SD; Pattison, JR; Pedlar, CR, 2012)	2.07
" The combination form of anti-cancer drugs with different mechanisms could decrease the dosage of employed anti-cancer drugs."	( Induction of apoptosis and non-apoptosis in human breast cancer cell line (MCF-7) by cisplatin and caffeine. Niknafs, B, 2011)	0.59
" Concomitant use of drugs metabolized by CYP2D6 may require dosage adjustment."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
" Administration of caffeine, with lower dosage than ED(50) (2."	( Caffeine interferes embryonic development through over-stimulating serotonergic system in chicken embryo. He, RR; Kurihara, H; Li, XD; Li, YF; Ma, ZL; Qin, Y; Tsoi, B; Yang, X, 2012)	2.15
" In adults, caffeine may interfere with sleep onset and have a dose-response effect similar to those seen during insomnia."	( Maternal caffeine consumption and infant nighttime waking: prospective cohort study. Domingues, MR; Matijasevich, A; Santos, IS, 2012)	1.17
"Female Sprague-Dawley rats were dosed daily by gavage for 28 days with synephrine from two different extracts."	( Physiological effects following administration of Citrus aurantium for 28 days in rats. Abdel-Rahman, A; Fabricant, D; George, NI; Hansen, DK; Pellicore, LS; White, GE, 2012)	0.38
" Each subject completed the test twice--once with a 3 mg·kg(-1) of body weight dose of caffeine and once with a placebo, with the dosage administered 60 minutes before commencement of exercise."	( The effect of caffeine on maximal oxygen uptake and vertical jump performance in male basketball players. Blackwell, GJ; Clarke, JC; Dale, DL; Hargreaves, JM; Tucker, MA, 2013)	0.97
"A number of studies have examined the association between coffee consumption and risk of bladder cancer, but uncertainty about the dose-response relationship remains."	( A dose-response meta-analysis of coffee consumption and bladder cancer. Jia, C; Tian, C; Zhou, Y, 2012)	0.38
" Dose-response relationship was assessed by restricted cubic spline model and bivariate random-effect meta-regression."	( A dose-response meta-analysis of coffee consumption and bladder cancer. Jia, C; Tian, C; Zhou, Y, 2012)	0.38
" In the present study, we investigated whether maternal caffeine dosing exacerbates the fetal CV response to acute maternal hypoxia during the primary morphogenesis period."	( Maternal hypoxia and caffeine exposure depress fetal cardiovascular function during primary organogenesis. Keller, BB; Momoi, N; Tinney, JP; Tobita, K, 2012)	0.94
" Meta-regression analysis revealed a positive dose-response relation between coffee intake and TC, LDL-C and TG."	( The effect of coffee consumption on serum lipids: a meta-analysis of randomized controlled trials. Cai, L; Liu, Z; Ma, D; Wang, P; Zhang, Y, 2012)	0.38
"We conducted a systematic review and a dose-response meta-analysis of prospective studies that assessed the relationship between habitual coffee consumption and the risk of heart failure."	( Habitual coffee consumption and risk of heart failure: a dose-response meta-analysis. Levitan, EB; Mittleman, MA; Mostofsky, E; Rice, MS, 2012)	0.38
" A dose-response pattern for total dietary caffeine intake was not observed."	( Maternal caffeine consumption and risk of congenital limb deficiencies. Bell, EM; Browne, ML; Burns, TL; Chen, L; Druschel, CM; Moslehi, R; Olney, RS; Romitti, PA; Schmidt, RJ, 2012)	1.06
"The objective of this study is to assess the effect of smoking and caffeine intake in the dosage of dopaminergic replacement therapy."	( Caffeine drinking, cigarette smoking, and dopaminergic replacement therapy dose in Parkinson's disease. Cervantes-Arriaga, A; Corona, T; Ojeda-López, C; Rodríguez-Violante, M, 2013)	2.07
" Clinical variables are useful to model a dosing nomogram for serum clozapine levels."	( Clinical predictors of serum clozapine levels in patients with treatment-resistant schizophrenia. Jacob, KS; Jacob, M; Kuruvilla, A; Poonkuzhali, B; Rajkumar, AP, 2013)	0.39
"Glucose metabolic changes in CM patients taking different dosage of analgesic during headache-free periods and clear distinctions in several brain regions were observed."	( Overuse of paracetamol caffeine aspirin powders affects cerebral glucose metabolism in chronic migraine patients. Di, W; Fang, Y; Luo, N; Miao, J; Qi, W; Shi, X; Tao, Y; Xiao, Z; Yi, C; Zhang, A; Zhang, X; Zhu, Y, 2013)	0.7
" Therefore, the proposed method is suitable for the routine control of these ingredients in multicomponent dosage forms."	( Capillary electrophoretic determination of antimigraine formulations containing caffeine, ergotamine, paracetamol and domperidone or metoclopramide. Alshehri, MM; Alzoman, NZ; Elshahed, MS; Maher, HM; Olah, IV; Rizk, MS; Sultan, MA, 2013)	0.62
"05) different from that of acarbose at the same dosage (50 mg/kg BW), which indicate that these fractions could be developed as potential anti-diabetic agents."	( Studies on the bioactivity of aqueous extract of pu-erh tea and its fractions: in vitro antioxidant activity and α-glycosidase inhibitory property, and their effect on postprandial hyperglycemia in diabetic mice. Chen, H; Chen, S; Hochstetter, D; Huang, Q; Wang, Y; Xu, P, 2013)	0.39
"In this study, a simple, specific and accurate reverse phase high performance liquid chromatographic method was developed for the simultaneous determination of nimesulide (NS), phenylephrine hydrochloride (PE), chlorpheniramine maleate (CPM) and caffeine anhydrous (CF) in pharmaceutical dosage forms."	( Development and validation of RP-HPLC method for simultaneous estimation of nimesulide, phenylephrine hydrochloride, chlorpheniramine maleate and caffeine anhydrous in pharmaceutical dosage form. Kumar, A; Nair, A; Saini, G; Sharma, R, )	0.51
" However, the effects of caffeine on bone metabolism are still controversial, and whether the dosage of caffeine influences osteogenic differentiation is yet to be clarified."	( Caffeine regulates osteogenic differentiation and mineralization of primary adipose-derived stem cells and a bone marrow stromal cell line. Chang, KL; Chen, KM; Shyu, HW; Su, SH; Su, SJ; Yeh, YT, 2013)	2.14
"In order to assess whether caffeine and theophylline have the same potency and efficacy to reverse the impairment of motor function caused by acute or chronic interruption of striatal dopamine transmission, a comparison of their dose-response relationship was made in the acute model of haloperidol-induced catalepsy, and the chronic model of unilateral lesion of the dopamine nigrostriatal pathway with 6-hydroxydopamine."	( Caffeine has greater potency and efficacy than theophylline to reverse the motor impairment caused by chronic but not acute interruption of striatal dopaminergic transmission in rats. Acuña-Lizama, MM; Alvarez-Cervera, FJ; Bata-García, JL; Góngora-Alfaro, JL, 2013)	2.13
"The aim of the study was to determine whether caffeine modifies the effects of alcohol on mood and psychomotor performance and to identify possible dose-response and temporal relationships."	( Effects of caffeine and alcohol on mood and performance changes following consumption of lager. Smith, AP, 2013)	1.04
" Sprague-Dawley rats were dosed daily by gavage for 28 days with 10 or 50 mg of synephrine/kg body weight from one of two different extracts; caffeine was added to some doses."	( Cardiovascular toxicity of Citrus aurantium in exercised rats. Abdel-Rahman, A; Fabricant, D; George, NI; Hansen, DK; Pellicore, LS; White, GE, 2013)	0.59
" The dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression."	( Coffee and caffeine intake and breast cancer risk: an updated dose-response meta-analysis of 37 published studies. Jiang, W; Jiang, X; Wu, Y, 2013)	0.78
" A linear dose-response relationship was found for breast cancer risk with coffee and caffeine, and the risk of breast cancer decreased by 2% (P=0."	( Coffee and caffeine intake and breast cancer risk: an updated dose-response meta-analysis of 37 published studies. Jiang, W; Jiang, X; Wu, Y, 2013)	1
" The system operation was tested with the extraction, separation and detection of propranolol and associated metabolites from drug dosed tissues, caffeine from a coffee bean, cocaine from paper currency, and proteins from dried sheep blood spots on paper."	( Continuous-flow liquid microjunction surface sampling probe connected on-line with high-performance liquid chromatography/mass spectrometry for spatially resolved analysis of small molecules and proteins. Kertesz, V; Van Berkel, GJ, 2013)	0.59
" Different doses of the drugs in a single dosage unit were produced, using a drop-on-demand inkjet printer by varying printing parameters such as the distance between jetted droplets (drop spacing) and the physical dimensions of the printed dosage forms."	( Behavior of printable formulations of loperamide and caffeine on different substrates--effect of print density in inkjet printing. Fors, D; Genina, N; Palo, M; Peltonen, J; Sandler, N, 2013)	0.64
" There was no dose-response relationship with SCC."	( Caffeine intake and risk of basal cell and squamous cell carcinomas of the skin in an 11-year prospective study. Green, AC; Hughes, MC; Miura, K; van der Pols, JC, 2014)	1.85
"A dose-response meta-analysis was carried out between Parkinson's disease (PD) risk, and coffee, tea and caffeine consumption."	( Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson's disease. Li, S; Qi, H, 2014)	0.87
" The dose-response relationship was assessed by restricted cubic spline."	( Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson's disease. Li, S; Qi, H, 2014)	0.66
"5 mg/day doses of caffeine significantly increased memory capability and the expression of hippocampal BDNF and TrkB in PS1/APP mice with a dose-response effect."	( Chronic caffeine treatment reverses memory impairment and the expression of brain BNDF and TrkB in the PS1/APP double transgenic mouse model of Alzheimer's disease. Han, K; Jia, N; Li, J; Min, LQ; Yang, L, 2013)	1.16
" The type of interaction between components was determined by isobolographic analysis or by analysis of the log dose-response curves for drug combination and drugs alone."	( Levetiracetam interacts synergistically with nonsteroidal analgesics and caffeine to produce antihyperalgesia in rats. Micov, AM; Stepanović-Petrović, RM; Tomić, MA, 2013)	0.62
"78 to 92, I(2)=0%) without significant differences in other dosage strata."	( Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies. Alves, LB; Caldeira, D; Costa, J; Ferreira, JJ; Martins, C; Pereira, H, 2013)	1.83
"Current compendial dissolution and disintegrating testing is unable to mimic physiological conditions affecting gastric drug release from immediate release dosage forms."	( Bio-relevant dissolution testing of hard capsules prepared from different shell materials using the dynamic open flow through test apparatus. Benameur, H; Cadé, D; Garbacz, G; Weitschies, W, 2014)	0.4
" A dose-response meta-analysis of prospective studies was conducted to assess the association between coffee and caffeine intake and T2DM incidence."	( Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies. Jiang, W; Jiang, X; Zhang, D, 2014)	1
" Dose-response relationship was assessed by restricted cubic spline."	( Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies. Jiang, W; Jiang, X; Zhang, D, 2014)	0.79
" Dose-response analysis suggested that incidence of T2DM decreased by 12 % [0."	( Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies. Jiang, W; Jiang, X; Zhang, D, 2014)	0.79
"The paper deals with formulation of caffeine into dermal semisolid dosage forms - hydrogels."	( [Evaluation of liberation of caffeine from dermal semisolids drugs]. Herdová, P; Kodadová, A; Vitková, Z, 2013)	0.96
" The aim of this study was to determine whether caffeine could have an effect on pupillary sleepiness waves, measured with the Pupillographic Sleepiness Test (PST) during routine clinical PST testing, where the caffeine dose-response of a participant cannot be registered before recording."	( The effect of caffeine on spontaneous pupillary oscillations. Lüdtke, H; Stuiber, G; Wilhelm, B; Wilhelm, H, 2014)	1.02
"These results suggest that a conservative (100 mg) dosage of caffeine may not have an impact on vocal acoustics and aerodynamics."	( Effects of caffeine on vocal acoustic and aerodynamic measures of adult females. Franca, MC; Schuette, A; Simpson, KO, 2013)	1.02
" Caffeine enhanced performance 24 h after administration according to an inverted U-shaped dose-response curve; this effect was specific to consolidation and not retrieval."	( Post-study caffeine administration enhances memory consolidation in humans. Borota, D; Chang, A; Keceli, G; Ly, M; Murray, E; Toscano, JP; Watabe, JM; Yassa, MA, 2014)	1.7
"Coffee consumption was inversely associated with the risk of type 2 diabetes in a dose-response manner."	( Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis. Bhupathiraju, SN; Chen, M; Ding, M; Hu, FB; van Dam, RM, 2014)	0.4
" The seemingly paradoxical use of both adenosine receptor agonists and antagonists as neuroprotective agents has been attributed to differences in dosage levels, drug delivery method, extracellular concentration of excitatory neurotransmitters and stage of disease progression."	( Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: a review. Díaz-Ríos, M; Rivera-Oliver, M, 2014)	0.88
" Increasing carbon dosage and contact time enhanced the removal of micropollutants."	( Adsorption characteristics of selected hydrophilic and hydrophobic micropollutants in water using activated carbon. Choi, DJ; Her, N; Kim, SK; Nam, SW; Zoh, KD, 2014)	0.4
" We conducted a meta-analysis to investigate the association between chronic exposure of caffeine and the risk of AF and to evaluate the potential dose-response relation."	( Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies. Cheng, M; Gu, D; Hu, Z; Huang, J; Lu, X, 2014)	2.07
"Gastroretentive drug delivery systems (GRDDS) play an important role in the delivery of drug substances to the upper part of the gastrointestinal tract; they offer a possibility to overcome the limited gastric residence time of conventional dosage forms."	( Floating gastroretentive drug delivery systems: Comparison of experimental and simulated dissolution profiles and floatation behavior. Alles, R; Eberle, VA; Gane, PA; Huwyler, J; Puchkov, M; Schoelkopf, J, 2014)	0.4
"United States Pharmacopeia (USP) dissolution methods are of limited usefulness for evaluating floating behavior and drug release of floating dosage forms."	( Floating gastroretentive drug delivery systems: Comparison of experimental and simulated dissolution profiles and floatation behavior. Alles, R; Eberle, VA; Gane, PA; Huwyler, J; Puchkov, M; Schoelkopf, J, 2014)	0.4
"Floating dosage forms based on FCC appear promising."	( Floating gastroretentive drug delivery systems: Comparison of experimental and simulated dissolution profiles and floatation behavior. Alles, R; Eberle, VA; Gane, PA; Huwyler, J; Puchkov, M; Schoelkopf, J, 2014)	0.4
"To compare the impact of caffeine on PPI expression in C57BL/6 mice by two dose-response experiments differing in terms of chronicity, regimen, and route of administration."	( Sensorimotor gating is disrupted by acute but not chronic systemic exposure to caffeine in mice. Dubroqua, S; Singer, P; Yee, BK, 2014)	0.93
" Two separate dose-response studies tested the acute effect of the selective A₁R antagonist, 1,3 dipropyl-8 cyclopentyl xanthine (DPCPX), and the selective A₂AR antagonist, 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c] (SCH 58261) (0."	( Sensorimotor gating is disrupted by acute but not chronic systemic exposure to caffeine in mice. Dubroqua, S; Singer, P; Yee, BK, 2014)	0.63
"Caffeine is widely used to treat apnea of prematurity, but the standard dosing regimen is not always sufficient to prevent apnea."	( Impact of daily high-dose caffeine exposure on developing white matter of the immature ovine brain. Atik, A; Cheong, J; De Matteo, R; Harding, R; Rees, S; Tolcos, M, 2014)	2.15
"To test these hypotheses, we examined heart rate and blood pressure before and after administration of placebo and 2 doses of caffeine (1 and 2 mg/kg) in prepubertal (8- to 9-year-olds; n = 52) and postpubertal (15- to 17-year-olds; n = 49) boys (n = 54) and girls (n = 47) by using a double-blind, placebo-controlled, dose-response design."	( Cardiovascular responses to caffeine by gender and pubertal stage. Bendlin, A; Graczyk, A; Sion, T; Temple, JL; Vattana, K; Ziegler, AM, 2014)	0.9
" Caffeine at a dosage of 5 mg/kg (moderate intake) or placebo tablets were administered orally at a mean time of 57 ± 13 minutes prior to the EPS."	( A prospective placebo controlled randomized study of caffeine in patients with supraventricular tachycardia undergoing electrophysiologic testing. Bernick, J; Lemery, R; Pecarskie, A; Wells, GA; Williams, K, 2015)	1.58
" We did not find a dose-response effect."	( Pharmacological interventions for sleepiness and sleep disturbances caused by shift work. Costa, G; Driscoll, TR; Isotalo, LK; Liira, J; Ruotsalainen, JH; Sallinen, M; Verbeek, JH, 2014)	0.4
"The median caffeine dosage was 300 mg."	( Caffeine and diuresis during rest and exercise: A meta-analysis. Antonio, J; Bishop, PA; Casa, DJ; Coca, A; Green, JM; Zhang, Y, 2015)	2.25
"AIF at the dosage of 50 mg/mL, effectively attenuated caffeine-induced wakefulness (P<0."	( Hypnotic effects of a novel anti-insomnia formula on Drosophila insomnia model. Chan, EH; Fung, KP; Ko, CH; Koon, CM; Lau, CB; Lee, KY; Leung, PC; Wing, YK; Yu, SL, 2016)	0.68
" We conducted meta-analysis of dose-response curves for associations between caffeine intake and spontaneous abortion, stillbirth, preterm delivery, low birth weight and small for gestational age (SGA) infants."	( Caffeine intake during pregnancy and adverse birth outcomes: a systematic review and dose-response meta-analysis. Cade, JE; Garrard, L; Greenwood, DC; Keogh, G; King, LG; Thatcher, NJ; Ye, J, 2014)	2.07
" We aim to assess this association using a systematic review and dose-response meta-analysis of prospective studies."	( Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis. Chen, LW; Chong, MF; Neelakantan, N; Pan, A; van Dam, RM; Wu, Y, 2014)	0.82
" Dose-response relationships were assessed using generalized least-squares trend estimation."	( Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis. Chen, LW; Chong, MF; Neelakantan, N; Pan, A; van Dam, RM; Wu, Y, 2014)	0.82
" Ingestion of these products in the form of tablets, capsules, or other solid dosage forms as weight loss aids, exercise performance enhancers, or energy boosters have once again brought their tolerability and efficacy into question."	( Multi-ingredient, caffeine-containing dietary supplements: history, safety, and efficacy. Gurley, BJ; Steelman, SC; Thomas, SL, 2015)	0.75
"In a dosage of 50 mg bid, eplerenone does not augment extracellular adenosine formation in healthy human subjects."	( The effect of eplerenone on adenosine formation in humans in vivo: a double-blinded randomised controlled study. Bilos, A; Deinum, J; Donders, AR; Riksen, NP; Rongen, GA; van den Berg, TN, 2014)	0.4
" Although increase in seizure duration was achieved for the majority of the ECT sessions, no dose-response correlation could be made."	( Pretreatment With Caffeine Citrate to Increase Seizure Duration During Electroconvulsive Therapy: A Case Series. Biglow, M; Chandra, S; Pica, T; Pinkhasov, A, 2016)	0.77
" This association demonstrated a dose-response relationship: OR=1."	( Maternal caffeine intake during pregnancy and risk of obesity in offspring: a prospective cohort study. Ferber, JR; Li, DK; Odouli, R, 2015)	0.83
" These results suggest that caffeine exposure can at first be benign, but that high dosage or prolonged exposure hinders functional recovery."	( Time-dependent bidirectional effects of chronic caffeine on functional recovery of the dorsal light reflex after hemilabyrinthectomy in the goldfish Carassius auratus. Brockhoff, BL; Goodson, NB; Huston, JP; Spieler, RE, 2015)	0.97
" In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men."	( Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review. Barulli, MR; Bonfiglio, C; Guerra, V; Logroscino, G; Osella, A; Panza, F; Pilotto, A; Sabbà, C; Seripa, D; Solfrizzi, V, 2015)	0.96
" Urine voided within 7 h after dosing was collected for a high-performance liquid chromatographic analysis of metabolites, and the urinary molar ratio of metabolites was used as marker for enzyme activity."	( Distribution of xanthine oxidase activity in a Nigerian population. Adehin, A; Bolaji, OO, 2015)	0.42
" The potential efficacy of these MN for paediatric dosing was investigated via in vitro and in vivo studies."	( Potential of hydrogel-forming and dissolving microneedles for use in paediatric populations. Caffarel-Salvador, E; Donnelly, RF; McCarthy, HO; McElnay, JC; Mooney, K; Tuan-Mahmood, TM; Woolfson, AD, 2015)	0.42
" A dose-response analysis suggested that risk of pregnancy loss rose by 19% for every increase in caffeine intake of 150 mg/day and by 8% for every increase in coffee intake of two cups per day."	( A meta-analysis of risk of pregnancy loss and caffeine and coffee consumption during pregnancy. Li, J; Song, JM; Tang, YL; Xin, CM; Zhang, J; Zhao, H, 2015)	0.89
"In the pharmaceutical field, tablets are the most common dosage forms for oral administration."	( Predictive model for tensile strength of pharmaceutical tablets based on local hardness measurements. Briancon, S; Hoc, T; Juban, A; Nouguier-Lehon, C; Puel, F, 2015)	0.42
" The formation of chlorate and perchlorate during electrochemical processes was observed, and a combined strategy to prevent this important drawback was successfully tested based on the application of low current densities with the simultaneous dosing of hydrogen peroxide."	( Conductive diamond electrochemical oxidation of caffeine-intensified biologically treated urban wastewater. Cañizares, P; Martín de Vidales, MJ; Millán, M; Pérez, JF; Rodrigo, MA; Sáez, C, 2015)	0.67
" CBD promoted an inverted U-shaped dose-response curve in the anxiety task; in the memory assessment, CBD in the dose of 5mg/Kg promoted the strongest effects without interfering with social and aggressive behavior."	( Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio). Antonioli, R; Bonan, CD; Capiotti, KM; Crippa, JA; da Silva, RS; Hallak, JE; Nazario, LR; Zuardi, AW, 2015)	1.86
" However, there are still uncertainties regarding effects on central nervous system development, time of discontinuation and dosing of the drug."	( Caffeine for preterm infants: current indications and uncertainties. Carnielli, VP; Nobile, S, 2015)	1.86
" This study demonstrates that caffeine supplementation at a 6 mg/kg dosage facilitates performances in MVIC and T(lim)."	( Effects of Gender Difference and Caffeine Supplementation on Anaerobic Muscle Performance. Chao, HH; Chen, HY; Tung, K; Wang, HS, 2015)	0.99
" Caffeine intake was not associated with cancer risk in a dose-response manner."	( Coffee, tea, caffeine intake, and the risk of cancer in the PLCO cohort. Boffetta, P; Buys, SS; Galeone, C; Gren, L; Hashibe, M; La Vecchia, C; Zhang, ZF, 2015)	1.7
"This is a dose-response (DR) meta-analysis to evaluate the association of coffee consumption on endometrial cancer (EC) risk."	( Coffee consumption and risk of endometrial cancer: a dose-response meta-analysis of prospective cohort studies. Li, H; Li, M; Luo, ML; Zhou, JG; Zhou, Q, 2015)	0.42
"Eligible studies were identified through a detailed algorithm and hand-search of eligible articles' references; thereafter, summary-effect estimates were calculated by leukemia subtype and dose-response meta-analyses were performed."	( Maternal and childhood consumption of coffee, tea and cola beverages in association with childhood leukemia: a meta-analysis. Baka, M; Diamantaras, AA; Hatzipantelis, E; Kantzanou, M; Kourti, M; Moschovi, M; Ntouvelis, E; Petridou, ET; Polychronopoulou, S; Sidi, V; Stiakaki, E; Thomopoulos, TP; Tzanoudaki, M, 2015)	0.42
" Any or low to moderate maternal cola consumption was also positively associated with overall leukemia (AL) and ALL, A linear trend between coffee and cola consumption and childhood leukemia was observed in the dose-response analyses."	( Maternal and childhood consumption of coffee, tea and cola beverages in association with childhood leukemia: a meta-analysis. Baka, M; Diamantaras, AA; Hatzipantelis, E; Kantzanou, M; Kourti, M; Moschovi, M; Ntouvelis, E; Petridou, ET; Polychronopoulou, S; Sidi, V; Stiakaki, E; Thomopoulos, TP; Tzanoudaki, M, 2015)	0.42
"Categorical and dose-response meta-analysis of prospective studies."	( Maternal caffeine intake during pregnancy and risk of pregnancy loss: a categorical and dose-response meta-analysis of prospective studies. Chen, LW; Chong, MF; Neelakantan, N; Pan, A; van Dam, RM; Wu, Y, 2016)	0.85
" In the dose-response analysis, each 100 mg/d increment in maternal caffeine intake (~1 cup of coffee) was associated with 7% (95% CI 3%, 12%) higher risk of pregnancy loss."	( Maternal caffeine intake during pregnancy and risk of pregnancy loss: a categorical and dose-response meta-analysis of prospective studies. Chen, LW; Chong, MF; Neelakantan, N; Pan, A; van Dam, RM; Wu, Y, 2016)	1.09
" We conducted a meta-analysis with a dose-response analysis to quantitatively summarize the evidence about the association between coffee and caffeine intakes and risk of depression."	( Coffee and caffeine consumption and depression: A meta-analysis of observational studies. Shen, X; Wang, L; Wu, Y; Zhang, D, 2016)	1.03
" Dose-response relationship was assessed by restricted cubic spline functions."	( Coffee and caffeine consumption and depression: A meta-analysis of observational studies. Shen, X; Wang, L; Wu, Y; Zhang, D, 2016)	0.82
" For dose-response analysis, evidence of a linear association was found between coffee consumption and depression, and the risk of depression decreased by 8% (relative risk = 0."	( Coffee and caffeine consumption and depression: A meta-analysis of observational studies. Shen, X; Wang, L; Wu, Y; Zhang, D, 2016)	0.82
"Accurate quantitative measurement of drugs and their metabolites is important as this can be used to establish long-term abuse of illicit materials as well as establish accurate drug dosing for legal therapeutics."	( Simultaneous multiplexed quantification of caffeine and its major metabolites theobromine and paraxanthine using surface-enhanced Raman scattering. Alharbi, O; Goodacre, R; Xu, Y, 2015)	0.68
" Random effects models, subgroup analyses, and dose-response analyses were performed."	( Coffee, tea, caffeine and risk of depression: A systematic review and dose-response meta-analysis of observational studies. Castellano, S; Galvano, F; Grosso, G; Micek, A; Pajak, A, 2016)	0.8
"Developing a pediatric oral formulation with an age-appropriate dosage form and taste masking of naturally bitter active pharmaceutical ingredients (APIs) are key challenges for formulation scientists."	( Rat Palatability Study for Taste Assessment of Caffeine Citrate Formulation Prepared via Hot-Melt Extrusion Technology. Patil, H; Pimparade, MB; Polk, AN; Repka, MA; Tiwari, RV; Ye, X, 2017)	0.71
" A significant increase in free amino groups was observed in TBs with a dose-response effect, while addition of PEF in bread produced a significant decrease (p<0."	( Effect of theanine and polyphenols enriched fractions from decaffeinated tea dust on the formation of Maillard reaction products and sensory attributes of breads. Andlauer, W; Culetu, A; del Castillo, MD; Fernandez-Gomez, B; Ullate, M, 2016)	0.43
" Dose-response relationship was assessed by restricted cubic spline."	( Coffee consumption and the risk of cutaneous melanoma: a meta-analysis. Li, X; Wang, J; Zhang, D, 2016)	0.43
" Dose-response analysis suggested cutaneous melanoma risk decreased by 3 % [0."	( Coffee consumption and the risk of cutaneous melanoma: a meta-analysis. Li, X; Wang, J; Zhang, D, 2016)	0.43
" A higher CCN loading, Oxone dosage and temperature greatly improved the caffeine degradation by CCN-activated Oxone."	( Efficient elimination of caffeine from water using Oxone activated by a magnetic and recyclable cobalt/carbon nanocomposite derived from ZIF-67. Chen, BC; Lin, KY, 2016)	0.97
" High purity, small serving size, and lack of clear dosing instructions may place users at risk of toxicity."	( Quantitative analysis of powdered caffeine products purchased from the Internet using liquid chromatography-quadrupole time-of-flight mass spectrometry. Beauchamp, GA; Gerona, R; Hendrickson, RG; Lin, T; Zeng, WZ, 2016)	0.71
" Overall, the population norm of the salivary metabolic ratio in a Singaporean Chinese population established in this study is distinct from individuals with liver disease or mild abnormal liver function tests and provides the benchmark for dosage adjustments of drugs metabolized by CYP1A2."	( Establishing population distribution of drug-metabolizing enzyme activities for the use of salivary caffeine as a dynamic liver function marker in a Singaporean Chinese population. Chia, HY; Ho, HK; Yau, WP, 2016)	0.65
" Further studies are needed to evaluate the influence of liver damage on paracetamol pharmacokinetics whenever repeated dosing is applied, to avoid possible drug accumulation."	( Bioavailability of paracetamol with/without caffeine in Egyptian patients with hepatitis C virus. Abdel-Aziz, AA; Ashour, AA; Atta, R; Botros, SS; El-Lakkany, NM; Hendawy, AS; Mansour, AM; Seif El-Din, SH, 2016)	0.7
" A simulation-based equation for personalized dosing of theophylline was derived."	( Application of a Physiologically Based Pharmacokinetic Model to Study Theophylline Metabolism and Its Interactions With Ciprofloxacin and Caffeine. Lightstone, FC; Navid, A; Ng, DM; Wong, SE, 2016)	0.64
" If data permit, meta-analysis and dose-response analysis will be conducted."	( Is caffeine intake a risk factor leading to infertility? A protocol of an epidemiological systematic review of controlled clinical studies. Cao, H; Feng, X; Liu, J; Ren, J; Yang, G, 2016)	1.06
"Lipopolysaccharide-activated cord blood monocytes (CBM) from 19 infants were exposed to caffeine (0-200 μmol/l) with or without previous exposure to A1R, A3R, or PDE IV antagonists to determine changes in dose-response curves."	( Mechanisms of modulation of cytokine release by human cord blood monocytes exposed to high concentrations of caffeine. Ahlawat, R; Chavez-Valdez, R; Gauda, EB; Wills-Karp, M, 2016)	0.87
"An analysis of calls to three poison centers for powdered caffeine found that exposures were uncommon, but did result in toxicity, and highlighted that the lack of clear dosing instructions on product packaging may place patients at risk of inadvertent overdose."	( A Retrospective Study of Clinical Effects of Powdered Caffeine Exposures Reported to Three US Poison Control Centers. Beauchamp, GA; Crouch, BI; Hendrickson, RG; Horowitz, BZ; Johnson, AR; Valento, M, 2016)	0.93
"Previous studies have shown that the blood pressure elevating effect of acute caffeine consumption was variable because of the heterogeneity of study participants, dosage of caffeine and study designs."	( Does a single cup of caffeinated drink significantly increase blood pressure in young adults? A randomised controlled trial. Chua, CZ; Lim, WY; Lin, KT; Teng, CL; Teo, RS; Yeo, JC, )	0.36
" The impact of obesity-related alterations on drug metabolism and its consequences for drug dosing remains largely unknown in both children and adults."	( The CYTONOX trial. Christensen, HR; Dalhoff, KP; Gade, C; Holm, JC; Holst, H; Mikus, G, 2016)	0.43
" The results are expected to be used in the future as a basis for drug dosing recommendations in obese children."	( The CYTONOX trial. Christensen, HR; Dalhoff, KP; Gade, C; Holm, JC; Holst, H; Mikus, G, 2016)	0.43
" The dose-response curve (DRCs) shows that the combination of rac-Flur (31."	( Antinociceptive Effect of Racemic Flurbiprofen and Caffeine Co-Administration in an Arthritic Gout-Type Pain in Rats. Espinosa-Juárez, JV; Jaramillo-Morales, OA; Liévano-Reyes, R; López-Muñoz, FJ; Pérez-Méndez, HI; Solís-Oba, A, 2016)	0.69
" Dosing regimen of 40/5 mg/kg q12h (loading dose/maintenance dose, time interval) led to similar endotracheal re-intubation rate but increased percentage of patients experiencing tachycardia compared to the standard regimen of 20/5 mg/kg q24h (44."	( Incorporating pharmacodynamic considerations into caffeine therapeutic drug monitoring in preterm neonates. Balch, AH; Korgenski, EK; Sherwin, CM; Ward, RM; Yu, T, 2016)	0.69
" Here, a 3-h caffeine/colcemid co-treatment before harvesting at 55 h post-exposure is used so that the dicentric analysis using Giemsa staining is based predominantly on lymphocytes released from the G2-block, increasing thus dicentric yield and enabling construction of a dose-response calibration curve with improved precision of high-dose estimates."	( Biodosimetry for High-Dose Exposures Based on Dicentric Analysis in Lymphocytes Released from the G2-Block by Caffeine. Dimitriou, P; Hatzi, V; Karachristou, I; Karaiskos, P; Karakosta, M; Pantelias, A; Pantelias, G; Terzoudi, GI; Thanassoulas, A, 2016)	1.02
"03), with the dose-response curve exhibiting a quadratic relationship."	( The Effects of Caffeine on Arousal, Response Time, Accuracy, and Performance in Division I Collegiate Fencers. Arent, SM; Doyle, TP; Lutz, RS; Pellegrino, JK; Sanders, DJ, 2016)	0.79
" However, the outcomes of previous investigations on this topic are inconclusive due to methodological differences, especially, in the dosage of the active ingredients and the test used to assess performance."	( Acute effects of caffeine-containing energy drinks on physical performance: a systematic review and meta-analysis. Casonatto, J; Del Coso, J; Polito, MD; Souza, DB, 2017)	0.79
" The meta-regression demonstrated a significant association between taurine dosage (mg) and performance (slope = 0."	( Acute effects of caffeine-containing energy drinks on physical performance: a systematic review and meta-analysis. Casonatto, J; Del Coso, J; Polito, MD; Souza, DB, 2017)	0.79
" There was some evidence of a dose-response effect."	( Consumption of energy drinks by children and young people: a rapid review examining evidence of physical effects and consumer attitudes. Cheetham, M; Crossley, SJ; Lake, AA; Riby, DM; Visram, S, 2016)	0.43
"Fused deposition modeling (FDM) 3-Dimensional (3D) printing is becoming an increasingly important technology in the pharmaceutical sciences, since it allows the manufacture of personalized oral dosage forms by deposition of thin layers of material."	( Fused-filament 3D printing of drug products: Microstructure analysis and drug release characteristics of PVA-based caplets. Basit, AW; Gaisford, S; Goyanes, A; Kobayashi, M; Martínez-Pacheco, R, 2016)	0.43
" Caffeine was administered in the caffeine group and control group at the same dosage at 12-24 hours after birth and before extubation respectively."	( [Effect of early caffeine treatment on the need for respirator therapy in preterm infants with respiratory distress syndrome]. Duan, YH; Han, JT; Su, P; Wei, QZ; Zhang, X, 2016)	1.68
" Our time-course and dose-response analyses for each of the three drugs represent so far the most detailed studies available serving as a foundation for future psychopharmacology experiments with zebrafish."	( Time-dependent interacting effects of caffeine, diazepam, and ethanol on zebrafish behaviour. Chow, H; Desai, P; Facciol, A; Fulcher, N; Gerlai, R; Nowicki, M; Tran, S; Tsang, B, 2017)	0.73
"Explore the occurrence of self-reported physiological stimulant and sedative side effects between sessions of AmED and alcohol only, and at varying ED dosage levels within AmED sessions."	( Combined use of alcohol and energy drinks: Dose relationship with self-reported physiological stimulation and sedation side effects. Bruno, R; Droste, N; Lubman, DI; Miller, P; Peacock, A; Pennay, A; Zinkiewicz, L, 2017)	0.46
"033) continued over time in a dose-response manner."	( The Relationship Between Caffeine Intake and Immunological and Virological Markers of HIV Disease Progression in Miami Adult Studies on HIV Cohort. Baum, MK; Campa, A; Fleetwood, C; George, F; Khan, H; Li, Y; Liuzzi, JP; Martinez, SS; Ramamoorthy, V; Rubens, M; Stewart, T, 2017)	0.76
"Aminophylline is as effective as caffeine for prevention of apneic spells in preterm neonates; however, dosage optimization needs to be done to reduce toxicity."	( Comparative Efficacy and Safety of Caffeine and Aminophylline for Apnea of Prematurity in Preterm (≤34 weeks) Neonates: A Randomized Controlled Trial. Bhat Y, R; Jayashree, P; Kamath, A; Lewis, LES; Najih, M; Shashikala, -; Shivakumar, M, 2017)	1.01
" We calculated relative risks (RRs) of HCC according to caffeinated and decaffeinated coffee consumption using a random-effects dose-response meta-analysis."	( Coffee, including caffeinated and decaffeinated coffee, and the risk of hepatocellular carcinoma: a systematic review and dose-response meta-analysis. Buchanan, R; Fallowfield, JA; Hayes, PC; Kennedy, OJ; Parkes, J; Roderick, P, 2017)	0.46
" Dose-response analyses did not reveal a clear lipolytic effect in both species."	( Pterostilbene Inhibits Lipogenic Activity similar to Resveratrol or Caffeine but Differently Modulates Lipolysis in Adipocytes. Belles, C; Briot, A; Carpéné, C; Fernández-Quintela, A; Gomez-Zorita, S; Portillo, MP, 2017)	0.69
" Further inquiry is warranted in large prospective studies and should include assessment of dose-response associations."	( Coffee consumption and risk of renal cell carcinoma. Antwi, SO; Arnold, ML; Cheville, JC; Custer, KM; Diehl, ND; Eckel-Passow, JE; Leibovich, BC; Parker, AS; Serie, DJ; Thiel, DD; Wu, KJ, 2017)	0.46
" Caffeine is a known ergogenic aid that could be dosed at 3 mg·kg to maximize benefits of mental alertness while limiting potential side effects."	( Fueling the Triathlete: Evidence-Based Practical Advice for Athletes of All Levels. Getzin, AR; Harkins, M; Milner, C, )	1.04
"To determine the disposition and effects of caffeine after administration using a new dosage form (AeroShot) that delivers caffeine by inspiration of a fine powder into the oral cavity and compare it to an equivalent dose of an oral solution (energy drink) as the reference standard."	( Comparison of caffeine disposition following administration by oral solution (energy drink) and inspired powder (AeroShot) in human subjects. Chen, F; Hu, ZY; Laizure, SC; Meibohm, B; Nelson, K; Parker, RB, 2017)	1.08
"tDCS dosed at 1800 provided 6 h of improved attentional accuracy and reaction times compared to the control group."	( Transcranial direct current stimulation versus caffeine as a fatigue countermeasure. Goodyear, C; McIntire, LK; McKinley, RA; Nelson, JM, )	0.39
"To determine the association between total, caffeinated and decaffeinated coffee consumption and melanoma risk a dose-response meta-analysis on prospective cohort studies were performed."	( Caffeinated and decaffeinated coffee consumption and melanoma risk: a dose-response meta-analysis of prospective cohort studies. Godos, J; Lafranconi, A; Marranzano, M; Micek, A; Pajak, A, 2018)	0.48
"There is growing need to develop efficient methods for early-stage drug discovery, continuous manufacturing of drug delivery vehicles, and ultra-precise dosing of high potency drugs."	( Printing of small molecular medicines from the vapor phase. Amidon, GE; Clarke, R; Fleck, E; Jones, CM; Mazzara, JM; Mehta, G; Raghavan, S; Rockwell, C; Schwendeman, A; Senabulya, N; Shalev, O; Shtein, M; Simopoulos, N; Sinko, PD, 2017)	0.46
" The effects of the treatment conditions, such as chlorine dosage and pH, and the water matrix components of natural organic matter (NOM), alkalinity, ammonia and halides, on the kinetics and reactive species in the degradation of four micropollutants, metronidazole (MDZ), nalidixic acid (NDA), diethyltoluamide (DEET) and caffeine (CAF), by the UV/chlorine process were investigated."	( Factors affecting the roles of reactive species in the degradation of micropollutants by the UV/chlorine process. Chen, L; Fang, J; Guo, K; Hou, S; Kong, X; Meng, F; Shang, C; Wu, Z; Xiao, H; Yang, X, 2017)	0.63
" However, the need to adjust the CF dosage to individuals, because some people are more sensitive to drugs than others, may constituted a limit to the CF effectiveness."	( Protective Effects of the Caffeine Against Neurodegenerative Diseases. Ficarra, S; Galtieri, A; Russo, A; Tellone, E, 2019)	0.81
" Additional studies are needed to assess the relationship between caffeine dosing and clinical benefits in patients with TTH and migraine."	( Caffeine in the management of patients with headache. Diener, HC; Garas, SY; Lipton, RB; Patel, K; Robbins, MS, 2017)	2.13
"To identify dosing strategies that will assure stable caffeine concentrations in preterm neonates despite changing caffeine clearance during the first 8 weeks of life."	( Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in Preterm Neonates. Datta, AN; Jost, K; Koch, G; Pfister, M; Schulzke, SM; van den Anker, J, 2017)	2.15
"A 3-step simulation approach was used to compute caffeine doses that would achieve stable caffeine concentrations in the first 8 weeks after birth: (1) a mathematical weight change model was developed based on published weight distribution data; (2) a pharmacokinetic model was developed based on published models that accounts for individual body weight, postnatal, and gestational age on caffeine clearance and volume of distribution; and (3) caffeine concentrations were simulated for different dosing regimens."	( Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in Preterm Neonates. Datta, AN; Jost, K; Koch, G; Pfister, M; Schulzke, SM; van den Anker, J, 2017)	2.15
"A standard dosing regimen of caffeine citrate (using a 20 mg/kg loading dose and 5 mg/kg/day maintenance dose) is associated with a maximal trough caffeine concentration of 15 mg/L after 1 week of treatment."	( Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in Preterm Neonates. Datta, AN; Jost, K; Koch, G; Pfister, M; Schulzke, SM; van den Anker, J, 2017)	2.19
"To evaluate the capacity for modafinil to be a perpetrator of metabolic drug-drug interactions by altering cytochrome P450 activity following a single dose and dosing to steady state."	( Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions using a model informed cocktail reaction phenotyping trial protocol. Mangoni, AA; Rowland, A; Sorich, MJ; van Dyk, M; Warncken, D, 2018)	0.48
"These data support consideration of the risk of clinically relevant metabolic drug-drug interactions perpetrated by modafinil when this drug is co-administered with drugs that are primarily cleared by CYP2C19 (single modafinil dose or steady state modafinil dosing) or CYP3A4 (steady state modafinil dosing only) catalysed metabolic pathways."	( Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions using a model informed cocktail reaction phenotyping trial protocol. Mangoni, AA; Rowland, A; Sorich, MJ; van Dyk, M; Warncken, D, 2018)	0.48
"Caffeine therapy for apnea of prematurity (AOP) remains one of the pillars of neonatal care, although more evidence to support dosing and timing of initiation and discontinuation are needed."	( Caffeine controversies. Carlo, WA; Gentle, SJ; Travers, CP, 2018)	3.37
" In this study, the permeability of human skin was compared using two synthetic membranes: cellulose acetate and Strat-M® membrane and lipophilic and hydrophilic compounds either as saturated or formulated solutions as well as marketed dosage forms."	( Membrane properties for permeability testing: Skin versus synthetic membranes. Dorrani, M; Goodyear, B; Haq, A; Joshi, V; Michniak-Kohn, B, 2018)	0.48
" Further studies should focus on the timing and dosage of caffeine to optimize the prevention of AKI."	( Association Between Early Caffeine Citrate Administration and Risk of Acute Kidney Injury in Preterm Neonates: Results From the AWAKEN Study. Askenazi, DJ; Boohaker, LJ; Carmody, JB; Charlton, JR; Griffin, RL; Guillet, R; Harer, MW; Selewski, DT; Swanson, JR, 2018)	1.03
"Pomalidomide is an immunomodulatory drug, and the dosage of 4 mg per day taken orally on days 1-21 of repeated 28-day cycles has been approved in the European Union and the United States to treat patients with relapsed/refractory multiple myeloma."	( In Vivo Assessment of the Effect of CYP1A2 Inhibition and Induction on Pomalidomide Pharmacokinetics in Healthy Subjects. Hoffmann, M; Li, Y; Liu, L; Palmisano, M; Reyes, J; Wang, X; Zhang, C; Zhou, S, 2018)	0.48
" We assessed the algorithm by comparing the caffeine-dosing strategies (timing and amount) it identified with the dosing strategies used in four experimental studies, involving total and partial sleep loss."	( Caffeine dosing strategies to optimize alertness during sleep loss. Balkin, TJ; Doty, TJ; Ramakrishnan, S; Reifman, J; Vital-Lopez, FG, 2018)	2.18
"We determined the influence of cumulative dosing of caffeine citrate on the neurodevelopmental outcomes of low birth weight (VLBW) infants at 18-22 months of postmenstrual age."	( Higher daily doses of caffeine lowered the incidence of moderate to severe neurodevelopmental disabilities in very low birth weight infants. Chouthai, NS; Gupte, A; Kamat, D; Lulic-Botica, M; Ma, MM; Mamilla, D; Patel, B; Ravichandran, S; Sharma, A; Thomas, R, 2019)	1.08
" We conducted a meta-analysis including a dose-response analysis to assess the relationship between caffeine consumed and incidence of AF."	( Does Caffeine Consumption Increase the Risk of New-Onset Atrial Fibrillation? Abdelfattah, R; Kamran, H; Kassotis, J; Lazar, J, 2018)	1.21
" In present study, we found that pregnant mice treated with moderate (5 mg/kg) or high (30 mg/kg) dosage of caffeine (intraperitoneally or orally) during preimplantation resulted in retention of early embryos in the oviduct, defective embryonic development, and impaired embryo implantation."	( Caffeine consumption during early pregnancy impairs oviductal embryo transport, embryonic development and uterine receptivity in mice. Chen, Q; Duan, E; Hwang, SJ; Kim, BH; Liu, S; Qian, J; Qu, Y; Shi, J; Ward, SM; Zhang, L; Zhang, X; Zhang, Y; Zhou, T, 2018)	2.14
"The decision-making process for estimating the optimal dosage is critical in clinical settings."	( Estimation of Caffeine Regimens: A Machine Learning Approach for Enhanced Clinical Decision Making at a Neonatal Intensive Care Unit (NICU). Shirwaikar, RD, 2018)	0.84
"27)], and a dose-response relationship was observed for duration of drinking tea and the amount of tea consumed [P for trend <0."	( Green tea consumption and risk of type 2 diabetes in Chinese adults: the Shanghai Women's Health Study and the Shanghai Men's Health Study. Cai, H; Gao, YT; Gerszten, RE; Ji, BT; Li, H; Liu, X; Shu, X; Shu, XO; Wang, T; Xiang, YB; Xu, W; Zheng, W, 2018)	0.48
" Analysed dosage forms contained cyproheptadine and dexamethasone in concentrations higher than therapeutic doses."	( Determination of synthetic pharmaceutical adulterants in herbal weight gain supplements sold in herb shops, Tehran, Iran. Akhgari, M; Bahmanabadi, L; Bazmi, E; Mousavi, Z; Saberi, N, 2018)	0.48
"Tablets for oral suspension (TOS) present a convenient alternative dosage form to conventional tablets."	( Stability investigation of FCC-based tablets for oral suspension with caffeine and oxantel pamoate as model drugs. Huwyler, J; Puchkov, M; Schoelkopf, J; Wagner-Hattler, L, 2019)	0.75
"32 mg/kg/inf) under a fixed ratio (FR) 1 schedule of reinforcement and generated full dose-response curves for methylone (0."	( Behavioral economic analysis of the reinforcing effects of "bath salts" mixtures: studies with MDPV, methylone, and caffeine in male Sprague-Dawley rats. Collins, GT; Gannon, BM; Mesmin, MP; Rice, KC; Sulima, A, 2019)	0.72
" In the source water system, the integrated AC-NF process with coagulation pretreatment (the alum dosage of 60 mg/L) achieved satisfactory performance (the removal efficiencies of three target compounds reached > 95%)."	( Performance evaluation of integrated adsorption-nanofiltration system for emerging compounds removal: Exemplified by caffeine, diclofenac and octylphenol. Chiang, PC; Dang, Z; Gong, B; Huang, CP; Huang, Z; Pan, SY; Wu, P, 2019)	0.72
" The dosage and administration of caffeine affect the ergogenic effects obtained following the ingestion of this substance."	( Effects of different dosages of caffeine administration on wrestling performance during a simulated tournament. Baker, JS; Del Coso, J; Farhani, F; Khodadoost, M; Lima-Silva, AE; Mokhtarzade, M; Negaresh, R; Talebvand, S; Willems, MET, 2019)	1.08
" The study demonstrates that HPC is a suitable solid binder for DoP printing and that 3D-DoP printing can be used to print robust dosage forms."	( Powder bed 3D-printing of highly loaded drug delivery devices with hydroxypropyl cellulose as solid binder. Baier, A; Haemmerli, A; Iliev, S; Infanger, S; Quodbach, J; Stoyanov, E, 2019)	0.51
"To investigate the effects of repeated caffeine dosing on neurobehavioral performance during sleep deprivation, we conducted a laboratory-based, randomized, double-blind, placebo-controlled, crossover, multi-dose study of repeated caffeine administration during 48 h of sleep deprivation."	( Randomized, double-blind, placebo-controlled, crossover study of the effects of repeated-dose caffeine on neurobehavioral performance during 48 h of total sleep deprivation. Hansen, DA; Layton, ME; Ramakrishnan, S; Reifman, J; Satterfield, BC; Van Dongen, HPA; Wesensten, NJ, 2019)	1
"The neurobehavioral effects of repeated caffeine dosing during sleep deprivation were most evident during the circadian alertness trough (i."	( Randomized, double-blind, placebo-controlled, crossover study of the effects of repeated-dose caffeine on neurobehavioral performance during 48 h of total sleep deprivation. Hansen, DA; Layton, ME; Ramakrishnan, S; Reifman, J; Satterfield, BC; Van Dongen, HPA; Wesensten, NJ, 2019)	1
" Cocrystallization via fluidized bed granulation represents a useful tool and a feasible alternative technique for the large scale manufacture of pharmaceutical cocrystals for solid dosage forms."	( In Situ Cocrystallization of Dapsone and Caffeine during Fluidized Bed Granulation Processing. Cabral, LM; Healy, AM; Todaro, V; Worku, ZA, 2019)	0.78
" Restricted cubic splines were used to model the dose-response association."	( Caffeinated and decaffeinated coffee consumption and risk of all-cause mortality: a dose-response meta-analysis of cohort studies. Cheng, C; Hu, D; Li, H; Li, L; Li, Q; Liu, F; Liu, L; Liu, Y; Sun, X; Wang, B; Wang, C; Yin, Z; Zhang, M; Zhang, R; Zhao, Y; Zhou, Q, 2019)	0.51
"The process of disintegration is a crucial step in oral drug delivery with immediate release dosage forms."	( Combined Application of MRI and the Salivary Tracer Technique to Determine the in Vivo Disintegration Time of Immediate Release Formulation Administered to Healthy, Fasted Subjects. Grimm, M; Hasan, M; Jedamzik, P; Koziolek, M; Kromrey, ML; Merdivan, S; Sager, M; Tzvetkov, MV; Weitschies, W, 2019)	0.51
" However, the extent of the ergogenic response to acute caffeine ingestion might greatly vary among individuals despite using the same dosage and timing."	( Challenging the Myth of Non-Response to the Ergogenic Effects of Caffeine Ingestion on Exercise Performance. Del Coso, J; Lara, B; Ruiz-Moreno, C; Salinero, JJ, 2019)	1
" However, there is some evidence that caffeine attenuates performance decrements in marksman accuracy caused by stress and fatigue if optimal dosing strategies are employed."	( The effects of caffeine on marksmanship accuracy and reaction time: a systematic review. Kim, Y; Torres, C, 2019)	1.14
" We searched in the PubMed and Web of Science databases through March 8, 2019, and conducted meta-analysis including linear and non-linear dose-response analyses."	( Coffee consumption and all-cause and cause-specific mortality: a meta-analysis by potential modifiers. Giovannucci, E; Je, Y; Kim, Y, 2019)	0.51
"To characterize the dosing and safety of off-label caffeine citrate in a contemporary cohort of extremely premature infants."	( Dosing and Safety of Off-label Use of Caffeine Citrate in Premature Infants. Bendel-Stenzel, E; Chhabra, R; Harper, B; Ku, L; Laughon, M; Moya, F; Payne, EH; Puia-Dumitrescu, M; Smith, PB; Soriano, A; Wade, KC; Zhao, J, 2019)	1.04
" Midazolam, caffeine, and TMU concentrations were assessed at baseline and following dosing of rifampicin (300 mg daily) for 7 days."	( Identification of the caffeine to trimethyluric acid ratio as a dietary biomarker to characterise variability in cytochrome P450 3A activity. Hopkins, A; Marshall, JC; Miners, JO; Rowland, A; Sorich, MJ; van Dyk, M; Wood, LS, 2019)	1.21
"The aim of the present study was to perform a dose-response meta-analysis of cohort studies on the association between dietary caffeine intake, different types of coffee consumption, and the risk of ovarian cancer."	( Caffeine, Type of Coffee, and Risk of Ovarian Cancer: A Dose-Response Meta-Analysis of Prospective Studies. Esmaillzadeh, A; Larijani, B; Milajerdi, A; Salari-Moghaddam, A; Surkan, PJ, 2019)	2.16
") dosing was started from D-8 and continued up to D-32."	( Repeated caffeine administration aggravates post-traumatic stress disorder-like symptoms in rats. Dangi, DS; Krishnamurthy, S; Prajapati, SK, 2019)	0.93
" Overall, an acute dosage of 100 mg CAF and 100 mg CA did not elicit any differences in anaerobic performance or in perceived measures of effort and fatigue in young males who habitually consume caffeine."	( The Effects of Caffeine and Citrus Aurantium on Performance During Repeated Maximal Anaerobic Exercise Bouts in Habitual Caffeine Users. Bailey, P; Bechke, EE; Kliszczewicz, B; McLester, CN; McLester, JR; Williamson, CM, 2021)	1.16
" However, the differences between sexes are evident in terms of body size, body composition, and hormonal functioning, which might cause different outcomes on performance for the same dosage of caffeine intake in men vs."	( Effect of Caffeine Supplementation on Sports Performance Based on Differences Between Sexes: A Systematic Review. Calleja-González, J; Del Coso, J; León-Guereño, P; Marques-Jiménez, D; Mielgo-Ayuso, J; Refoyo, I, 2019)	1.11
"While the developed preterm model for the prediction of PK behaviour in preterm patients is not intended to replace clinical studies, it can potentially help with deciding on first-time dosing in this population and study design in the absence of clinical data."	( Preterm Physiologically Based Pharmacokinetic Model. Part II: Applications of the Model to Predict Drug Pharmacokinetics in the Preterm Population. Abduljalil, K; Jamei, M; Johnson, TN; Pan, X; Pansari, A, 2020)	0.56
" Escalating dosing regimens seem to provide additional benefit in select infants, but grave toxicity has also been documented with early utilization of high-dose caffeine."	( Caffeine Therapy in Preterm Infants: The Dose (and Timing) Make the Medicine. McPherson, C; Rostas, SE, 2019)	2.15
"Frogs have permeable skin, so transdermal delivery provides a practical alternative to traditional dosing routes."	( Percutaneous absorption between frog species: Variability in skin may influence delivery of therapeutics. Berger, L; Glass, BD; Llewelyn, VK, 2020)	0.56
" We raised the question of the appropriate caffeine dosing regimen for BRA in this postterm population."	( Caffeine treatment for bronchiolitis-related apnea in the pediatric intensive care unit. Brossier, D; Denis, M; Faucon, C; Goyer, I; Heuzé, N; Jokic, M; Porcheret, F, 2020)	2.26
"cit, CAF and PAP in pure powder and in combined tablets dosage form without interference from excipients."	( Development and Validation of Chromatographic Methods for Simultaneous Determination of Paracetamol, Orphenadrine Citrate and Caffeine in Presence of P-aminophenol; Quantification of P-aminophenol Nephrotoxic Impurity Using LC-MS/MS. Boltia, SA; Elzanfaly, ES; Soudi, AT; Zaazaa, HE, 2020)	0.76
" Further research into caffeine dosage and timing postpartum is required to establish its efficacy."	( Caffeine supplementation at birth, but not 8 to 12 h post-birth, increased 24 h pre-weaning mortality in piglets. Hebart, ML; Kind, K; Nowland, TL; van Wettere, WHEJ, 2020)	2.31
" Furthermore, dose-response relationships were examined using generalized least squares regression models."	( Coffee consumption and risk of bladder cancer: a pooled analysis of 501,604 participants from 12 cohort studies in the BLadder Cancer Epidemiology and Nutritional Determinants (BLEND) international study. Brinkman, M; Dai, Y; Grant, EJ; Gunter, M; Hemon, B; van den Brandt, P; van Osch, F; Weiderpass, E; Wesselius, A; White, E; Yu, EYW; Zeegers, MP, 2020)	0.56
" The FDM paradigm involving hot-melt extrusion for making 3D-printable drug-loaded filaments as intermediate products for tablet manufacturing has been gaining attention for the decentralized on-site production of personalized dosage forms."	( Simplification of fused deposition modeling 3D-printing paradigm: Feasibility of 1-step direct powder printing for immediate release dosage form production. Fanous, M; Gold, S; Hirsch, S; Imanidis, G; Muller, S; Ogorka, J, 2020)	0.56
" The impact of pH, temperature, adsorbent dosage and thermodynamic studies were deeply analyzed."	( Removal of caffeine, nicotine and amoxicillin from (waste)waters by various adsorbents. A review. Anastopoulos, I; Bonilla-Petriciolet, A; Manariotis, ID; Mittal, A; Núñez-Delgado, A; Orfanos, AG; Pashalidis, I; Sellaoui, L; Tatarchuk, T, 2020)	0.95
" While this technique produces dose-response data which fit very well to a linear-quadratic model for exposures to low linear energy transfer (LET) radiation and for doses up for 5 Gy, limitations to the accuracy of this method arise at larger doses."	( Cytogenetically-based biodosimetry after high doses of radiation. Brenner, DJ; Cunha, L; Garty, G; Harken, A; Perrier, JR; Pujol-Canadell, M; Shuryak, I, 2020)	0.56
" Myocytes superfused with 3-morpholinosydnonimine N-ethylcarbamide (SIN-1), an ONOO- donor, decreased the amplitude of Ca2+ transients and contraction in a dose-response (1-200 μM) manner."	( Peroxynitrite-Induced Intracellular Ca2+ Depression in Cardiac Myocytes: Role of Sarco/Endoplasmic Reticulum Ca2+ Pump. Escalante, B; Flores-Tamez, V; Rios, A, 2019)	0.51
" Based on pharmacokinetics, safety, and efficacy data, and PBPK modeling, dosing modifications for ribociclib recommend avoiding concurrent use of strong CYP3A inhibitors/inducers, and caution regarding using CYP3A substrates with narrow therapeutic indices."	( Ribociclib Drug-Drug Interactions: Clinical Evaluations and Physiologically-Based Pharmacokinetic Modeling to Guide Drug Labeling. Chakraborty, A; Dhuria, SV; Elmeliegy, M; He, H; Heimbach, T; Huth, F; Ji, Y; Miller, M; Samant, TS; Schiller, H; Umehara, K, 2020)	0.56
"The aim of the study was to evaluate the suitability of the current caffeine dosing regimen for the Chinese population using modelling and simulation approach."	( Developmental population pharmacokinetics of caffeine in Chinese premature infants with apnoea of prematurity: A post-marketing study to support paediatric labelling in China. Gao, XB; Jacqz-Aigrain, E; Jiang, ZH; Ni, SQ; Wang, CH; Wu, YE; Yang, F; Zhao, W; Zheng, Y, 2021)	1.12
" Monte Carlo simulation demonstrated that 80% (loading dose) and 98% (maintenance dose) of premature infants treated with a labelled dosing regimen attained the concentration target range of 5-20 mg/L."	( Developmental population pharmacokinetics of caffeine in Chinese premature infants with apnoea of prematurity: A post-marketing study to support paediatric labelling in China. Gao, XB; Jacqz-Aigrain, E; Jiang, ZH; Ni, SQ; Wang, CH; Wu, YE; Yang, F; Zhao, W; Zheng, Y, 2021)	0.88
" The labelled dosing regimen is suitable for Chinese premature infants."	( Developmental population pharmacokinetics of caffeine in Chinese premature infants with apnoea of prematurity: A post-marketing study to support paediatric labelling in China. Gao, XB; Jacqz-Aigrain, E; Jiang, ZH; Ni, SQ; Wang, CH; Wu, YE; Yang, F; Zhao, W; Zheng, Y, 2021)	0.88
" Among both observational studies and meta-analyses, there were frequent reports of significant dose-response associations suggestive of causation, and frequent reports of no threshold of consumption below which associations were absent."	( Maternal caffeine consumption and pregnancy outcomes: a narrative review with implications for advice to mothers and mothers-to-be. James, JE, 2021)	1.04
" N = 12 subjects underwent three 48 h periods of total sleep deprivation with different caffeine dosing regimens."	( Robustness of inter-individual differences in slow wave sleep for daytime sleep periods after total sleep deprivation with or without caffeine administration: potential implications for around-the-clock operations. Erwin, JA; Hansen, DA; Layton, ME; Paech, GM; Satterfield, BC; Skeiky, L; Van Dongen, HPA, )	0.56
" We review the evidence regarding the efficacy and safety of standard caffeine dosing and alternative dosing approaches, including the use of high dose caffeine and routine dose adjustments for age."	( Caffeine for preterm infants: Fixed standard dose, adjustments for age or high dose? Patel, RM; Saroha, V, 2020)	2.23
" Although sleep deprivation (SD) is widely considered as an independent risk factor for cognition retardations, however, little is well understood about the synergistic role of caffeine dosage and SD for cognitive performance."	( Caffeine-related effects on cognitive performance: Roles of apoptosis in rat hippocampus following sleep deprivation. Huang, P; Huang, X; Li, H; Wang, P; Xie, G, 2021)	2.26
"The Caffeine for Apnea of Prematurity (CAP) trial showed that caffeine was safe when used with standard dosing and provided both pulmonary and neurological benefits to preterm infants."	( National and international guidelines for neonatal caffeine use: Are they evidenced-based? Eichenwald, EC, 2020)	1.37
" To achieve this aim, subjects were told that they were participating in a study to determine the dosage response (low or high) of caffeine on neuromuscular fatigue when in fact no caffeine was given during the experiment."	( Perceived Consumption of a High-Dose Caffeine Drink Delays Neuromuscular Fatigue. Elhaj, HM; Imam, O; Malek, MH; Page, BW; Vitale, JM, 2022)	1.2
" Alongside this rising trend, a simple, accurate, inexpensive and flexible method to produce personalized dosage forms of a wide variety of supplements would be beneficial to both the industry players and individual consumers."	( 3D printing of four-in-one oral polypill with multiple release profiles for personalized delivery of caffeine and vitamin B analogues. Goh, WJ; Ho, PCL; Hu, J; Lim, SH; Pastorin, G; Tan, SX, 2021)	0.84
" Future clinical practice should be directed by an evidence-based approach including automated supplemental oxygen, minimizing the use of medications for gastroesophageal reflux, optimal timing and dosage of caffeine therapy, and standardization of alarm limits and discharge monitoring protocols."	( Are we over-treating hypoxic spells in preterm infants? Conlon, S; Di Fiore, JM; Martin, RJ, 2021)	0.81
" So far, the veracity of their labeling in terms of the dosage and cause/effect relationship aimed at the consumer."	( Caffeine Health Claims on Sports Supplement Labeling. Analytical Assessment According to EFSA Scientific Opinion and International Evidence and Criteria. Estevan Navarro, P; Gil-Izquierdo, A; González-Díaz, C; Jiménez-Alfageme, R; Martínez-Sanz, JM; Medina, S; Perales, A; Sospedra, I, 2021)	2.06
" A dose-response to sham caffeine ingestion was not evident on cognitive or endurance performance in healthy individuals, regardless of their convictions about caffeine's ergogenicity."	( Belief in caffeine's ergogenic effect on cognitive function and endurance performance: A sham dose-response study. Cox, GR; Delang, N; Desbrow, B; Irwin, C; McCartney, D, 2021)	1.33
"This pharmacokinetic (PK) drug-interaction trial investigated the effects of repeated dosing of a plant-derived pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex in the United States and Epidyolex in Europe; 100 mg/mL oral solution) on caffeine clearance via modulation of cytochrome P450 (CYP) 1A2 activity in healthy adults."	( A Phase 1 Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Trial to Investigate the Effect of Cannabidiol on the CYP1A2 Probe Caffeine in Healthy Subjects. Critchley, D; Tayo, B; Thai, C, 2021)	1
" Values of BIA parameters increased after 30-min of coffee consumption, independently of the caffeine dosage (all p < 0."	( The influence of coffee consumption on bioelectrical impedance parameters: a randomized, double-blind, cross-over trial. Gonzalez, MC; Lukaski, H; Mota, JF; Oto, GL; Prado, CM; Tibaes, JRB; Trottier, CF, 2022)	0.94
" This case study shows that individual PK profiles can be predicted more accurately by considering individual attributes and that personalized PBPK models could be a valuable tool for model-informed precision dosing approaches in the future."	( Data-driven personalization of a physiologically based pharmacokinetic model for caffeine: A systematic assessment. Blank, LM; Burghaus, R; Fendt, R; Hofmann, U; Kerb, R; Kuepfer, L; Lippert, J; Schaeffeler, E; Schlender, JF; Schneider, ARP; Schwab, M; Yilmaz, A, 2021)	0.85
" The goal of this study was to assess the efficacy of coagulation/flocculation/sedimentation (C/F/S), adsorption onto two types of powdered activated carbon (PAC)/sedimentation (PAC/S) and the combination of these two processes in different dosing sequences (PAC/C/F/S) and with/without ultrafiltration (powdered activated carbon/ultrafiltration-PAC/UF, coagulation/UF-CoA/UF) for the removal of selected micropollutants from river water."	( Fate of Benzophenone, Benzophenone-3 and Caffeine in Lab-Scale Direct River Water Treatment by Hybrid Processes. Bogunović, M; Ivančev-Tumbas, I; Marjanović, T, 2021)	0.89
" For drug factors, a dose-response relationship may exist but findings are inconsistent."	( How does caffeine influence memory? Drug, experimental, and demographic factors. Madan, CR; Zhang, RC, 2021)	1.04
" However, compilations of the magnitude of the effect of caffeine on anxiety and panic attacks are lacking and potential dose-response relationships have not been examined."	( Effects of caffeine on anxiety and panic attacks in patients with panic disorder: A systematic review and meta-analysis. Frick, A; Klevebrant, L, )	0.77
"In the present systematic review and meta-analysis, we aimed to examine the acute effects of placebo-controlled caffeine challenge on occurrence of panic attacks and subjective anxiety in patients with PD and healthy controls (HC), including dose-response relationships."	( Effects of caffeine on anxiety and panic attacks in patients with panic disorder: A systematic review and meta-analysis. Frick, A; Klevebrant, L, )	0.73
" The restricted range of caffeine employed [400-750 mg] and few studies (3) not using 480 mg prevented any meaningful analysis of a dose-response relationship."	( Effects of caffeine on anxiety and panic attacks in patients with panic disorder: A systematic review and meta-analysis. Frick, A; Klevebrant, L, )	0.82
" The restricted dose range used prevented assessment of dose-response relationships."	( Effects of caffeine on anxiety and panic attacks in patients with panic disorder: A systematic review and meta-analysis. Frick, A; Klevebrant, L, )	0.52
" Studies of caffeine in women suggest the physiological responder status and caffeine habituation may contribute to caffeine's efficacy, with a potential plateau in the dose-response relationship of performance enhancement."	( Dietary Supplements for Athletic Performance in Women: Beta-Alanine, Caffeine, and Nitrate. Hackney, AC; Murphy, MJ; Rushing, BR; Sumner, SJ, 2022)	1.33
"Randomized controlled clinical trials were included; sample composed of physically active or trained adults; CAF should be offered/ingested before exercise, with dosage between 100 and 400 mg or between 2 and 6 mg/kg and administration/ingestion route analogous in the protocols; studies required to present results of HRV indices before and after exercise."	( Caffeine intake and its influences on heart rate variability recovery in healthy active adults after exercise: A systematic review and meta-analysis. Benjamim, CJR; Bueno Júnior, CR; Garner, DM; Gonzaga, LA; Luciano de Almeida, M; Porto, AA; Valenti, VE, 2022)	2.16
" We performed the current updated systematic review and dose-response meta-analysis of coffee consumption and caffeine intake and risk of fracture to quantify this association."	( Coffee consumption and caffeine intake in relation to risk of fractures: a systematic review and dose-response meta-analysis of observational studies. Asoudeh, F; Bagheri, A; Esmaillzadeh, A; Larijani, B, 2023)	1.43
" Dose-response relationship was examined using linear and non-linear dose-response analyses."	( Coffee consumption and caffeine intake in relation to risk of fractures: a systematic review and dose-response meta-analysis of observational studies. Asoudeh, F; Bagheri, A; Esmaillzadeh, A; Larijani, B, 2023)	1.22
" To provide in-detail practical guidelines for the real-life application of MF countermeasures, more research must be performed into the underlying mechanisms and into the optimal dosage and time of application/intake."	( How to Tackle Mental Fatigue: A Systematic Review of Potential Countermeasures and Their Underlying Mechanisms. De Pauw, K; De Wachter, J; Habay, J; Meeusen, R; Proost, M; Rattray, B; Roelands, B; Van Cutsem, J, 2022)	0.72
" The aim of the study is the evaluation of the effectiveness of a multi-ingredient pre-workout supplement (MIPS) containing beta-alanine, L-citrulline malate, arginine alpha-ketoglutarate, L-taurine, L-tyrosine and caffeine compared to an exact dosage of anhydrous caffeine in bench press strength endurance, feeling scale (FS), felt arousal scale (FAS) and session rating of perceived exertion (sRPE)."	( Effects of Multi-Ingredient Pre-Workout Supplement and Caffeine on Bench Press Performance: A Single-Blind Cross-Over Study. Aksenov, MO; Kruszewski, A; Kruszewski, M; Merchelski, M; Pągowski, Ł; Tabęcki, R, 2022)	1.15
" The RCS results suggested an approximately linear dose-response relationship between the aforementioned metabolites and cognitive performance."	( Associations between urinary caffeine and caffeine metabolites and cognitive function in older adults. Cai, J; Cen, M; Chen, X; Fu, X; Li, H; Song, L; Wu, J; Yao, T, 2023)	1.2
"The optimal caffeine dosing in extremely premature neonates remains elusive."	( Caffeine dosing in premature neonates: impact of birth weight on a pharmacokinetic simulation study. Johnson, PN; Lim, SY; May, CB; Miller, JL, 2023)	2.73
"Higher-than-standard caffeine dosing may be needed for extremely premature neonates, especially for those with lower birth weights."	( Caffeine dosing in premature neonates: impact of birth weight on a pharmacokinetic simulation study. Johnson, PN; Lim, SY; May, CB; Miller, JL, 2023)	2.67
"Extremely premature neonates with a lower birth weight may require a higher weight-based caffeine dosing due to their higher weight-adjusted clearance and shorter half-lives."	( Caffeine dosing in premature neonates: impact of birth weight on a pharmacokinetic simulation study. Johnson, PN; Lim, SY; May, CB; Miller, JL, 2023)	2.57
"The presentation of 3D printing in drug innovation especially focuses on the advancement of patient-centered dosage forms based on the structural design."	( A Recent Review On 3D-Printing: Scope and Challenges with Special Focus on Pharmaceutical Field. Doolaanea, AA; Kumar, M; Mandal, UK; Singh, S, 2022)	0.72
" By reviewing these supplements' mechanisms, evidence relating directly to improving sports performance, and ideal dosing strategies, we provide a reference for athletes and medical staff to personalize supplementation strategies."	( The Impact of Supplements on Sports Performance for the Trained Athlete: A Critical Analysis. Fredericson, M; Kaufman, MW; Roche, M, 2022)	0.72
" Caffeine was administered daily by gavage for 8 weeks at a dosage of 20 mg/kg for low dose (LD) group and 60 mg/kg for high dose (HD) group while the third group served as control (CNT)."	( Chronic caffeine ingestion improves memory and learning and increases neuronal population and dendritic length in the hippocampus of adult mice. Adekanmbi, AJ; Femi-Akinlosotu, OM; Ighogboja, OO; Olopade, F; Shokunbi, MT, 2021)	1.97
" The aims of this study were to develop and evaluate population pharmacokinetic (PPK) models of caffeine in preterm infants through comprehensive screening of covariates and then to propose model-informed precision dosing of caffeine for this population."	( Population pharmacokinetic modeling of caffeine in preterm infants with apnea of prematurity: New findings from concomitant erythromycin and AHR genetic polymorphisms. Chen, F; Cheng, R; Dai, HR; Ding, XS; Guo, HL; He, X; Hu, YH; Jiao, Z; Liu, Y; Lu, KY; Xu, J, 2022)	1.21
" Capmatinib 400 mg bid was administered from day 4 on a continuous dosing schedule."	( Effect of capmatinib on the pharmacokinetics of substrates of CYP3A (midazolam) and CYP1A2 (caffeine) in patients with MET-dysregulated solid tumours. Chen, X; Cui, X; Giovannini, M; Isambert, N; Kapoor, S; López-López, R; Mau-Sorensen, M; Pognan, N; Quinlan, M; Rahmanzadeh, G; You, B, 2023)	1.13
" Studies investigating the association between caffeine and alcohol consumption and IVF/ICSI outcomes were included, and studies reporting the consumption amount were analyzed using a one-stage robust error meta-regression-based method to explore potential dose-response relation."	( The association between caffeine and alcohol consumption and IVF/ICSI outcomes: A systematic review and dose-response meta-analysis. Li, N; Li, Y; Rao, W; Yao, Q, 2022)	1.29
" Our goal was to exploit the food supplements to mimic the topical antivirals' functions but circumventing their severe side effects, which has limited the necessary dosage needed to exhibit the desired antiviral activity."	( Modeling studies on the role of vitamins B1 (thiamin), B3 (nicotinamide), B6 (pyridoxamine), and caffeine as potential leads for the drug design against COVID-19. Aghamohammadi, M; França, TCC; Goncalves, AS; LaPlante, SR; Shahdousti, P; Sirouspour, M, 2022)	0.94
" A longer duration of therapy has a higher risk of medication non-adherence due to higher costs and inappropriate dosage forms."	( Evaluation of pharmaceutically compounded oral caffeine on the impact of medication adherence and risk of readmission among preterm neonates: A single-center quasi-experimental study. Ali, A; Ambreen, G; Aslam, MS; Hussain, K; Kumar, M; Salat, MS; Saleem, SM; Shah, SAA; Tahir, A, 2022)	0.98
" The number of parental complaints about cost, ampoule usage, medication drawing issue, wastage, inappropriate dosage form, and longer duration of therapy reduced significantly in post-phase."	( Evaluation of pharmaceutically compounded oral caffeine on the impact of medication adherence and risk of readmission among preterm neonates: A single-center quasi-experimental study. Ali, A; Ambreen, G; Aslam, MS; Hussain, K; Kumar, M; Salat, MS; Saleem, SM; Shah, SAA; Tahir, A, 2022)	0.98
"PCC dispensation in the appropriate dosage form at discharge effectively reduced cost, non-adherence to therapy, and risk of hospital readmissions."	( Evaluation of pharmaceutically compounded oral caffeine on the impact of medication adherence and risk of readmission among preterm neonates: A single-center quasi-experimental study. Ali, A; Ambreen, G; Aslam, MS; Hussain, K; Kumar, M; Salat, MS; Saleem, SM; Shah, SAA; Tahir, A, 2022)	0.98
" CAF dosage did not moderate this effect."	( Does Caffeine Increase Fat Metabolism? A Systematic Review and Meta-Analysis. Conger, SA; Millard-Stafford, ML; Tuthill, LM, 2023)	1.42
" The dosage of these varies depending on the drink chosen."	( Cardiovascular and Cerebrovascular Response to RedBull® Energy Drink Intake in Young Adults. Costa, R; Rocha, C; Santos, H, 2023)	0.91
"Analytical techniques must be sensitive, specific, and accurate to assess the active pharmaceutical ingredients in pharmaceutical dosage forms."	( An effective and stability-indicating method development and optimization utilizing the Box-Behnken design for the simultaneous determination of acetaminophen, caffeine, and aspirin in tablet formulation. Ettaboina, SK; Gundla, R; Katari, NK; Muchakayala, SK; Satheesh, B; Yenda, P, 2023)	1.11
" LRSUGs provided recommendations about dosing (n = 108, 83%), frequency of use (n = 72, 55%), and when to use (n = 86, 66%)."	( Lower-risk substance use guidelines accessible by youth. Benoit, C; Card, KG; Koenig, B; Moebes, ZR, 2023)	0.91
"4 mg/kg), while dose-response studies ranged from 1 to 12 mg/kg."	( The Long Way to Establish the Ergogenic Effect of Caffeine on Strength Performance: An Overview Review. Del Coso, J; Giráldez-Costas, V; Mañas, A; Salinero, JJ, 2023)	1.16
" Though widely recognized dosage regimes have been used for decades, higher doses have been suggested to further improve neonatal outcomes."	( Caffeine dosing regimens in preterm infants with or at risk for apnea of prematurity. Brattström, P; Bruschettini, M; Davis, PG; Onland, W; Russo, C; Soll, R, 2023)	2.35
" Recently completed and future trials should report long-term neurodevelopmental outcome of children exposed to different caffeine dosing strategies in the neonatal period."	( Caffeine dosing regimens in preterm infants with or at risk for apnea of prematurity. Brattström, P; Bruschettini, M; Davis, PG; Onland, W; Russo, C; Soll, R, 2023)	2.56
"Apnea of prematurity can be treated with a body-weight-adjusted dosage of caffeine."	( Preliminary Study on the Development of Caffeine Oral Solid Form 3D Printed by Semi-Solid Extrusion for Application in Neonates. Aubert, A; Begu, S; Roche, A; Rossi, JC; Sanchez-Ballester, NM; Soulairol, I, 2023)	1.41
" In addition to that, it suggests that the added utility of not only the CLZ metabolizing enzymes but also POR, which is crucial for proper CYP activity, to guide CLZ dosing might be useful for clinical decision-making."	( The Potential Role of Baskak, B; Demirbugen Oz, M; Dural, E; Gumustas, M; Kir, Y; Ozdemir, F; Suzen, HS; Tok, KC; Ulusoy, M, )	0.13
"Through 3D printing (3DP), many parameters of solid oral dosage forms can be customised, allowing for truly personalised medicine in a way that traditional pharmaceutical manufacturing would struggle to achieve."	( 3D printing tablets for high-precision dose titration of caffeine. Cao, Y; Krueger, L; Miles, JA; Popat, A; Ward, J; Zheng, Z, 2023)	1.16
" Sampling method switching from "wet" matrices to "dry" DBS will facilitate and support the precision dosing of caffeine for preterm infants."	( From "wet" matrices to "dry" blood spot sampling strategy: a versatile LC-MS/MS assay for simultaneous monitoring caffeine and its three primary metabolites in preterm infants. Chen, F; Cheng, R; Dai, HR; Ding, XS; Guo, HL; Hu, YH; Shen, X; Wang, WJ; Xu, J, 2024)	1.86
"(5) Optimal dosing and timing are approximately two to four cups (approximately 473-946 ml or 16-32 oz."	( International society of sports nutrition position stand: coffee and sports performance. Anderson, DE; Antonio, J; Campbell, BI; Campbell, SC; Escalante, G; Kalman, DS; Kerksick, CM; Kreider, RB; Lowery, LM; Nelson, MT; Scanlon, KF; Stack, A; VanDusseldorp, TA; Ziegenfuss, TN, 2023)	0.91
" The screening and the subsequent dosage revealed the following substances: cocaine (86 ng/mL), benzoylecgonine (383 ng/mL), cocaethylene (17 ng/mL), ecgonine methyl ester (130 ng/mL), caffeine, cuscohygrine, cinnamoylcocaine and synephrine."	( Mariani wine: What's really in it? Analysis of the most popular tonic drink of the 19th century after 100 years of storage. Arbouche, N; de Lestrange, A; Kintz, P; Raul, JS, 2024)	1.63
" Therefore, we aimed to examine the impact of caffeine supplementation on blood pressure (BP) by conducting a systematic review and dose-response meta-analysis of randomized controlled clinical trials (RCTs)."	( The effects of caffeine supplementation on blood pressure in adults: A systematic review and dose-response meta-analysis. Abbas-Hashemi, SA; Asbaghi, O; Hosseininasab, D; Rastgoo, S; Shiraseb, F, 2023)	1.52
" The non-linear dose-response analysis detected the dosage of supplementation >400 mg/day is effective for increasing DBP (p = 0."	( The effects of caffeine supplementation on blood pressure in adults: A systematic review and dose-response meta-analysis. Abbas-Hashemi, SA; Asbaghi, O; Hosseininasab, D; Rastgoo, S; Shiraseb, F, 2023)	1.26