simvastatin

Research Excerpts

Overview

Simvastatin (SV) is a common hypolipidemic drug in clinical medicine. It can reduce cholesterol biosynthesis by inhibiting hydroxyl-methyl-glutaryl coenzyme A reductase. Previous in vitro and in vivo reports showed that it may have therapeutic effects in treating leiomyomas.

Excerpt	Reference	Relevance
"Simvastatin (SV) is a common hypolipidemic drug in clinical medicine that can reduce endogenous cholesterol biosynthesis by inhibiting hydroxyl-methyl-glutaryl coenzyme A reductase. "	( Simvastatin affects the PPARα signaling pathway and causes oxidative stress and embryonic development interference in Mugilogobius abei. Li, K; Nie, X; Tang, T; Wang, C; Wang, Y, 2021)	3.51
"Simvastatin is an antihyperlipidemic drug, and previous in vitro and in vivo reports showed that it may have therapeutic effects in treating leiomyomas."	( Simvastatin Inhibits Wnt/β-Catenin Pathway in Uterine Leiomyoma. Afrin, S; Borahay, MA; El Sabeh, M; Saha, SK, 2021)	2.79
"Simvastatin serves as an effective therapeutic potential in the treatment of dental disease via alternating proliferation of dental pulp stem cells. "	( Simvastatin treatment promotes proliferation of human dental pulp stem cells via modulating PI3K/AKT/miR-9/KLF5 signalling pathway. He, DE; Wang, JH, 2021)	3.51
"Simvastatin (SV) is a hypolipidemic agent, and it is the 2nd most widely prescribed lipid-lowering drug. "	( Detection and characterization of simvastatin and its metabolites in rat tissues and biological fluids using MALDI high resolution mass spectrometry approach. Al-Wabli, RI; Attwa, MW; Kadi, AA; Rahman, AFMM; Yin, W, 2022)	2.44
"Simvastatin is an antioxidant with lipid-lowering effects, which is commonly used to treat CHF."	( Simvastatin Combined with Resistance Training Improves Outcomes in Patients with Chronic Heart Failure by Modulating Mitochondrial Membrane Potential and the Janus Kinase/Signal Transducer and Activator of Transcription 3 Signaling Pathways. Wang, J; Wang, X; Wen, C; Yan, K, 2022)	2.89
"Simvastatin is a prodrug of the potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. "	( Effect of simvastatin on osteogenesis of the extremity bones in aging rats. Chen, S; Li, H; Liu, M; Tang, J; Wang, M; Xi, Y, 2023)	2.76
"Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase and has been found to have protective effects against several bacterial infections. "	( Simvastatin Inhibits Huy, TXN; Kim, H; Kim, S; Lee, H; Lee, J; Min, W; Nguyen, TT; Reyes, AWB, 2022)	3.61
"Simvastatin is a cholesterol-lowering drug known for its endothelial cell pleiotropic properties."	( Association between single nucleotide polymorphism SLCO1B1 gene and simvastatin pleiotropic effects measured through flow-mediated dilation endothelial function parameters. Ardiana, M; Dewi, IP; Kusuma Wardhani, LF; Nugraha, RA; Puspitasari, M; Shonafi, KA, )	1.09
"Simvastatin is a well-known safe cholesterol-lowering medication that has been recently shown to suppress cancer progression."	( Simvastatin Induces Apoptosis And Suppresses Hepatocellular Carcinoma Induced In Rats. Amin, MN; El-Gayar, AM; Elleithi, YA, 2023)	3.07
"Simvastatin (SMV) is a poorly soluble oral cholesterol-lowering drug that may aid diabetic wound healing."	( Simvastatin-Releasing Nanofibrous Peptide Hydrogels for Accelerated Healing of Diabetic Wounds. Abolmaali, SS; Azarpira, N; Heidari, R; Janipour, Z; Najafi, H; Özyılmaz, ED; Tamaddon, AM, 2023)	3.07
"Simvastatin is a type of statins with anti-cancer activity, but its effect on colon cancer cells remains unclear."	( Simvastatin induces pyroptosis via ROS/caspase-1/GSDMD pathway in colon cancer. Liu, Y; Long, Y; Peng, M; Xie, W; Yi, L; Zhang, B, 2023)	3.07
"Simvastatin is a lipid‑lowering drug, which is commonly used to prevent or treat risk factors of cardiovascular diseases with a significant anti‑atherogenic effect."	( Simvastatin promotes endothelial dysfunction by activating the Wnt/β‑catenin pathway under oxidative stress. Du, X; He, Z; Hua, L; Wan, L; Wu, Y; Yan, N, 2019)	2.68
"Simvastatin is a semi-synthetic, highly lipophilic statin, and has several side effects."	( Differential effects of simvastatin on membrane organization and dynamics in varying phases. Chattopadhyay, A; Sahu, SS; Sarkar, P; Shrivastava, S, 2019)	1.54
"Simvastatin is an anti-hyperlipidemic drug which reduces the cholesterol synthesis and also has anti-inflammatory, immunomodulatory and anti-microbial action against the bacteria. "	( Effectiveness of Simvastatin 1% oral gel and mouthwash used as an adjunct treatment of scaling and root planning in the treatment of periodontal diseases. Asadullah, K; Hasan, F; Iftakhar, K; Ikram, R; Simjee, SU, 2019)	2.3
"Simvastatin (Sim) is a cholesterol-lowering drug and has been reported to inhibit tumor growth."	( Simvastatin re-sensitizes hepatocellular carcinoma cells to sorafenib by inhibiting HIF-1α/PPAR-γ/PKM2-mediated glycolysis. Chen, K; Dai, W; Feng, J; Guo, C; Ji, J; Kong, R; Li, J; Li, S; Mao, Y; Mo, W; Wu, J; Wu, L; Xu, X; Yu, Q; Zhang, J, 2020)	2.72
"Simvastatin appears to be a promising therapeutic strategy in this setting."	( Erythrocyte-derived microvesicles induce arterial spasms in JAK2V617F myeloproliferative neoplasm. Blanc-Brude, O; Boulanger, CM; Camara, F; Dagher, T; Davy, H; Devue, C; Dingli, F; El Mdawar, MB; Hatem, SN; James, C; Kheloufi, M; Lasselin, J; Loew, D; Merchant, S; Mougenot, N; Plessier, A; Poisson, J; Rautou, PE; Souyri, M; Tanguy, M; Villeval, JL, 2020)	1.28
"Simvastatin is a lipophilic statin that can enhance klotho expression."	( The neuroprotective effect of simvastatin on the cerebellum of experimentally-induced diabetic rats through klotho upregulation: An immunohistochemical study. Abd-Elhady, SL; El-Shahat, MA; Morsy, AI; Shams, AM; Youssef, OM, 2020)	1.57
"Simvastatin (SIM) is a commonly used cholesterol-lowering drug that can reduce the risk of major cardiovascular events. "	( A safety, tolerability, and pharmacokinetic study of a novel simvastatin silica-lipid hybrid formulation in healthy male participants. Abuhelwa, AY; Clifton, P; Joyce, P; Meola, TR; Prestidge, CA, 2021)	2.31
"Simvastatin is a translational drug that may be used to induce local bone formation. "	( Osteogenic effects in a rat osteoporosis model and femur defect model by simvastatin microcrystals. Jia, J; Leng, H; Song, C; Wang, H; Wu, C; Xu, Y; Zhang, C; Zhang, Q; Zhu, J, 2021)	2.3
"Simvastatin (SV) is a typical lipid-lowering agent detected widely in waters, so its latent toxic effects to fish are deserved of concern. "	( Simvastatin affects Nrf2/MAPK signaling pathway and hepatic histological structure change in Gambusia affinis. Bao, S; Lin, J; Nie, X; Wang, C; Xie, M, 2021)	3.51
"Simvastatin, which acts as an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), is widely used to manage cardiovascular diseases."	( Simvastatin attenuates spatial memory impairment via inhibiting microgliosis and apoptotic cell death against ethanol induced neurotoxicity in the developing rat hippocampus. Hojati, V; Jafari, M; Khaksari, M; Vaezi, G, 2021)	2.79
"Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (CoA) reductase (HMGCR), the rate-limiting enzyme of the mevalonate (MVA) pathway for the cholesterol biosynthesis."	( Targeting cholesterol biosynthesis promotes anti-tumor immunity by inhibiting long noncoding RNA SNHG29-mediated YAP activation. Che, L; Huo, J; Li, J; Li, Y; Liu, Y; Mo, H; Ni, W; Qin, C; Xu, Y; Yao, S; Zhou, A; Zhou, R; Zhou, Y, 2021)	1.34
"Simvastatin is a hypolipidemic drug that inhibits hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase to control elevated cholesterol, or hypercholesterolemia. "	( Simvastatin prevents lipopolysaccharide-induced septic shock in rats. Da, XW; He, AD; Long, D; Wu, XL; Yu, L, 2017)	3.34
"Simvastatin is an important lipid-lowering agent with anti-inflammatory activity."	( Anti-inflammatory effects of simvastatin in nonsteroidal anti-inflammatory drugs-induced small bowel injury. Cho, JH; Chung, JW; Jeong, AR; Kim, EJ; Kim, EK; Kim, JH; Kim, KO; Kim, YJ; Kwon, KA; Park, DK, 2017)	1.47
"Simvastatin is a HMG-CoA reductase inhibitor widely used to lower plasma cholesterol and to protect against cardiovascular risk factors. "	( Simvastatin ameliorates ionizing radiation-induced apoptosis in the thymus by activating the AKT/sirtuin 1 pathway in mice. Huang, F; Liao, L; Tao, X; Tao, Y; Yang, H; Zhao, X, 2017)	3.34
"Simvastatin is a promising new drug for the treatment of endometriosis. "	( Effect of simvastatin on monocyte chemoattractant protein-1 expression in endometriosis patients: a randomized controlled trial. Pumipichet, S; Rattanasiri, S; Sophonsritsuk, A; Waiyaput, W; Weerakiet, S, 2017)	2.3
"Simvastatin is a drug commonly used to reduce the cholesterol level. "	( Influence of simvastatin on red blood cell line in porcine bone marrow. Babińska, I; Gonkowski, S; Otrocka-Domagała, I; Pomianowski, A; Rytel, L; Snarska, A; Sobiech, P; Wysocka, D; Żarczyńska, K, 2017)	2.27
"Simvastatin is a cholesterol-lowing reagent that is derived synthetically from the fermentation of Aspergillus terreus. "	( Kruppel-like factor 4 (KLF-4) plays a crucial role in simvastatin (SVT)-induced differentiation of rabbit articular chondrocytes. Kim, SJ; Yu, SM, 2018)	2.17
"Simvastatin (Sim) is a widely known drug in the treatment of hyperlipidemia, which has attracted so much attention in bone regeneration due to its potential osteoanabolic effect. "	( Preparation of emulsifying wax/glyceryl monooleate nanoparticles and evaluation as a delivery system for repurposing simvastatin in bone regeneration. Czech, T; Eskinazi-Budge, A; Kunzler, J; Manickavasagam, D; Novak, K; Oyewumi, MO, 2018)	2.13
"Simvastatin is a statins that is able to competitively inhibit the activity of 3‑hydroxy‑3‑methylglutaryl‑coenzyme A reductase."	( Low‑frequency ultrasound and microbubbles combined with simvastatin promote the apoptosis of MCF‑7 cells by affecting the LATS1/YAP/RHAMM pathway. Chen, C; Li, H; Wang, D, 2018)	1.45
"Simvastatin is a semisynthetic cholesterol-lowering medication and one of the top-selling statins in the world. "	( Engineering Saccharomyces cerevisiae for production of simvastatin. Bond, CM; Tang, Y, 2019)	2.2
"Simvastatin is a cholesterol-lowering drug that is prescribed to lower the risk of cardiovascular disease following high levels of blood cholesterol. "	( Coenzyme Q10 does not improve peripheral insulin sensitivity in statin-treated men and women: the LIFESTAT study. Dela, F; Dohlmann, TL; Hansen, M; Helge, JW; Kelly, B; Kuhlman, AB; Morville, T, 2019)	1.96
"Simvastatin (SIM), which is a lipid-lowering agent is known to have an anabolic effect on bone."	( Simvastatin attenuates tibial bone loss in rats with type 1 diabetes and periodontitis. Bak, EJ; Cha, JH; Kim, A; Kim, AR; Kim, JH; Sohn, Y; Yoo, YJ, 2018)	2.64
"Simvastatin (Svt) is a classic lipid-lowering drug that is widely used in the treatment of hypercholesterolemia and hypertriglyceridemia, while berberine chloride (Bbr) is a novel hypolipidemic agent and its blood-lipid-reducing mechanism is distinct from traditional drugs."	( Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: an open-label, randomized, parallel study in healthy Chinese subjects. Li, G; Qiu, F; Sun, Y; Zhao, L; Zhao, M, 2019)	1.47
"Simvastatin is a lipid-lowering drug in the pharmaceutical group statins. "	( Interaction of the cholesterol reducing agent simvastatin with zwitterionic DPPC and charged DPPG phospholipid membranes. Koçak, M; Kucuk Baloglu, F; Sariisik, E; Severcan, F, 2019)	2.21
"Simvastatin is a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor with multiple targets and effects. "	( Simvastatin protects photoreceptors from oxidative stress induced by all-trans-retinal, through the up-regulation of interphotoreceptor retinoid binding protein. Bahrami, B; Gillies, M; Murray, M; Shen, W; Wang, K; Wang, Y; Yao, W; Zeng, S; Zhang, T; Zhou, F; Zhu, L; Zhu, M, 2019)	3.4
"Simvastatin is a cholesterol-lowering drug via inhibiting HMG-CoA reductase, thereby inhibiting protein prenylation."	( Simvastatin enhances chemotherapy in cervical cancer via inhibition of multiple prenylation-dependent GTPases-regulated pathways. Ma, L; Pan, Q; Xu, J, 2020)	2.72
"Simvastatin (SIM) is a widely used anticholesterolemic drug that blocks the biosynthesis of cholesterol. "	( Effect of simvastatin on bovine intramuscular and subcutaneous adipocytes proliferation and gene expression Jin, Q; Liu, GF; Tan, XW; Wan, FC; Wei, C; Zhao, HB, 2020)	2.4
"Simvastatin is an inhibitor of the 3-hydroxy-3-methylglutaryl-CoA reductase used for decreasing low density lipoprotein (LDL)-cholesterol in patients. "	( Insulin prevents and reverts simvastatin-induced toxicity in C2C12 skeletal muscle cells. Bouitbir, J; Krähenbühl, S; Sanvee, GM, 2019)	2.25
"Simvastatin is an HMG-CoA reductase inhibitor that exerts pleiotropic effects beyond simple low-density lipoprotein lowering and has a similar impact on the differentiation of bone marrow stromal cells and peripheral blood mononuclear cells."	( In vitro Differentiation of Hair Follicle Stem Cell into Keratinocyte by Simvastatin Babakhani, A; Hashemi, P; Mohajer Ansari, J; Nobakht, M; Ramhormozi, P, 2019)	1.47
"Simvastatin is a widely used cholesterol-adjusting drug that selectively inhibits the 3-hyrdoxy-3-methylglutaryl-coenzyme A reductase, leading to decreased cholesterol biosynthesis. "	( Simvastatin downregulates HER2 via upregulation of PEA3 to induce cell death in HER2-positive breast cancer cells. Cao, X; Pan, Y; Sha, S; Zhang, T; Zhao, T; Zhao, Z, 2012)	3.26
"Simvastatin is a hypolipidemic drug used in atherosclerosis. "	( Application of design of experiments to optimizing novel gastroretentive drug delivery of simvastatin. Chabukswar, A; Jagdale, S; Kuchekar, B; Kurhe, P, 2013)	2.05
"Simvastatin (SMV) is a specific competitive inhibitor of 3-hydroxy-2-methyl-glutaryl coenzyme A reductase. "	( Simvastatin local drug delivery in smokers with chronic periodontitis: a randomized controlled clinical trial. Bajaj, P; Kumari, M; Naik, SB; Pradeep, AR; Rao, NS, 2013)	3.28
"Simvastatin is a cholesterol-lowering drug which exhibits numerous pleiotropic effects including anti-cancer activity. "	( Simvastatin induces caspase-dependent apoptosis and activates P53 in OCM-1 cells. Li, YX; Wang, Y; Wu, YZ; Xu, SL; Xu, WJ; Yang, HY; Zhao, MS, 2013)	3.28
"Simvastatin (SV) is a widely used drug for the treatment of hypercholesterolemia in humans. "	( Thermal stability of simvastatin under different atmospheres. Bernardes, CE; Cordeiro, C; Dias, A; Diogo, HP; Minas Da Piedade, ME; Oliveira, MC; Simões, RG, 2014)	2.16
"Simvastatin is an important regulator on NADPH subunits mRNA expressions and p47(phox)/p22(phox) interaction. "	( [Simvastatin attenuates oxidized low density lipoprotein induced oxidative stress in human umbilical vein endothelial cells via downregulating NADPH oxidase activity]. Cui, L; Guo, R; Zhang, L, 2014)	2.76
"Simvastatin (SMV) is a cholesterol-lowering drug that directly inhibits HMG-CoA reductase."	( Simvastatin and dipentyl phthalate lower ex vivo testicular testosterone production and exhibit additive effects on testicular testosterone and gene expression via distinct mechanistic pathways in the fetal rat. Beverly, BE; Foster, PM; Furr, JR; Gray, LE; Lambright, CS; McIntyre, BS; Sampson, H; Travlos, G; Wilson, VS, 2014)	2.57
"Simvastatin is a drug with demonstrated anti-inflammatory and antifibrotic effects in many tissues but had not previously been studied in the context of rotator cuff tears."	( Simvastatin reduces fibrosis and protects against muscle weakness after massive rotator cuff tear. Bedi, A; Davis, ME; Gumucio, JP; Harning, JA; Korn, MA; Mendias, CL; Saripalli, AL, 2015)	2.58
"Simvastatin is a statin with pleiotropic effects that can also act as an anti-oxidant agent, and these pharmacologic properties may contribute to its potential anti-cancer activity."	( Effects of simvastatin on cell viability and proinflammatory pathways in lung adenocarcinoma cells exposed to hydrogen peroxide. D'Agostino, B; Falcone, D; Gallelli, L; Maselli, R; Mesuraca, M; Navarra, M; Pelaia, G; Savino, R; Scaramuzzino, M; Spaziano, G; Terracciano, R, 2014)	1.51
"Simvastatin (SIM) is a lipophilic statin that has potential benefits for prevention and treatment of several types of malignancies. "	( Optimizing long-circulating liposomes for delivery of simvastatin to C26 colon carcinoma cells. Achim, M; Alupei, MC; Banciu, M; Licarete, E; Luca, L; Muntean, D; Porfire, A; Tomuta, I; Vlase, L, 2015)	2.11
"Simvastatin potassium is a hypolipidemic drug used with exercise, diet, and weight-loss to control elevated cholesterol, or hypercholesterolemia. "	( Preparation and evaluation of multi particulates drug delivery system using natural polymers. Baig, T; Sheikh, H; Srivastava, A; Tripathi, PK; Tripathi, S, 2015)	1.86
"Simvastatin is a HMG-CoA reductase Inhibitor and a substrate of CYP3A4. "	( A pharmacokinetic drug-drug interaction model of simvastatin and clarithromycin in humans. Chaiwong, K; Lohitnavy, M; Methaneethorn, J; Pongpanich, K; Sonsingh, P, 2014)	2.1
"Simvastatin is an HMG-CoA reductase inhibitor commonly used in the clinic to treat hypercholesterolemia. "	( Simvastatin increases excitability in the hippocampus via a PI3 kinase-dependent mechanism. Herron, CE; Hughes, B; Métais, C, 2015)	3.3
"Simvastatin is a cholesterol-lowering drug with immunomodulatory, anti-inflammatory, and antifibrotic effects."	( The possible protective effect of simvastatin and pioglitazone separately and in combination on bleomycin-induced changes in mice thin skin. Balaha, M; Kandeel, S, 2015)	1.42
"Simvastatin is a synthetic lipid lowering drug and Nigella sativa seeds found helpful in controlling hyperlipidemia."	( Comparative evaluation of Nigella sativa (Kalonji) and simvastatin for the treatment of hyperlipidemia and in the induction of hepatotoxicity. Majeed, A; Muneera, KE; Naveed, AK, 2015)	1.39
"Simvastatin is an efficient inhibitor of cholesterol synthesis that has various myotoxic consequences."	( Structural analysis of alterations in zebrafish muscle differentiation induced by simvastatin and their recovery with cholesterol. Atella, GC; Benchimol, M; Campos, LM; Costa, ML; Herculano-Houzel, S; Mermelstein, C; Midlej, V; Rios, EA, 2015)	1.36
"Simvastatin is a statin used to lower low-density lipoprotein cholesterol, but has limitations in patients on complicated regimens due to concerns about drug-drug interactions. "	( Comparative efficacy of pitavastatin and simvastatin in patients with hypercholesterolemia: a meta-analysis of randomized controlled clinical trials. Cui, L; Ma, N, 2015)	2.13
"Simvastatin (SIM) is a lipid-soluble inhibitor of hydroxy-3-methylglutaryl coenzyme A reductase with multiple reported therapeutic benefits. "	( Simvastatin prevents isoproterenol-induced cardiac hypertrophy through modulation of the JAK/STAT pathway. Al-Manee, RZ; Al-Oteibi, MM; Al-Rasheed, NM; Al-Shareef, SA; Hasan, IH; Mahmoud, AM; Mohamad, RA, 2015)	3.3
"Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor commonly used to reduce serum cholesterol. "	( Intravenous Administration of Simvastatin Improves Cognitive Outcome following Severe Traumatic Brain Injury in Rats. Boutté, AM; Gilsdorf, J; Lu, XC; Mountney, A; Shear, DA; Tortella, FC, 2016)	2.17
"Simvastatin is an antilipemic drug that promotes inhibition of HMG-CoA reductase. "	( Modulating effect of simvastatin on the DNA damage induced by doxorubicin in somatic cells of Drosophila melanogaster. Nepomuceno, JC; Orsolin, PC; Silva-Oliveira, RG, 2016)	2.2
"Simvastatin is a cholesterol-lowering drug, inhibiting 3-hydroxy-3-methylglutaryl-coenzyme CoA (HMG-CoA) reductase. "	( Simvastatin Reduces Cancerogenic Potential of Renal Cancer Cells via Geranylgeranyl Pyrophosphate and Mevalonate Pathway. Jurida, K; Kneip, N; Marzi, I; Relja, B; Woschek, M, 2016)	3.32
"Simvastatin is a lipid lowering drug whose beneficial role on bone metabolism was discovered in 1999. "	( Role of Simvastatin on fracture healing and osteoporosis: a systematic review on in vivo investigations. Moshiri, A; Oryan, A; Sharifi, AM, 2016)	2.31
"Simvastatin (SV) is a drug from the statin class, currently used orally as an anti-cholesterolemic drug. "	( Could simvastatin be considered as a potential therapy for chronic lung diseases? A debate on the pros and cons. Colombo, P; Ong, HX; Traini, D; Tulbah, AS; Young, PM, 2016)	2.36
"Simvastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor widely used for the treatment of hypercholesterolemia. "	( Simvastatin induces insulin resistance in L6 skeletal muscle myotubes by suppressing insulin signaling, GLUT4 expression and GSK-3β phosphorylation. Kokkola, T; Modi, S; Yaluri, N, 2016)	3.32
"Simvastatin is a common medication prescribed for hypercholesterolemia that accelerates local bone formation. "	( Simvastatin Exposure and Rotator Cuff Repair in a Rat Model. Behrens, SB; Coleman, SH; Deren, ME; Dines, JS; Doty, S; Drakos, MC; Ehteshami, JR, 2017)	3.34
"Simvastatin (SMV) is a specific competitive inhibitor of 3-hydroxy-2-methylglutaryl coenzyme A reductase that promotes bone formation. "	( Clinical Efficacy of Subgingivally Delivered 1.2 mg Simvastatin in the Treatment of Patients with Aggressive Periodontitis: A Randomized Controlled Clinical Trial. Abhilash, A; Gupta, A; Kalra, N; Kudyar, N; Malgaonkar, N; Pradeep, AR; Saquib, S, )	1.82
"Simvastatin is a competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway required for the biosynthesis of cholesterol and higher isoprenoids such as geranylgeranyl pyrophosphate (GGPP). "	( HMG-CoA reductase inhibitor simvastatin overcomes bortezomib-induced apoptosis resistance by disrupting a geranylgeranyl pyrophosphate-dependent survival pathway. Berges, C; Daniel, V; Fuchs, D; Naujokat, C; Opelz, G, 2008)	2.08
"Simvastatin is a cholesterol-lowering agent whose functional significance and neuroprotective mechanism in ischemic brain injury is not yet solved. "	( Molecular analysis of endoplasmic reticulum stress response after global forebrain ischemia/reperfusion in rats: effect of neuroprotectant simvastatin. Kaminska, B; Kaplán, P; Lehotský, J; Pavlíková, M; Sivonová, M; Tatarková, Z; Urban, P, 2009)	2
"Simvastatin is a pro-drug of the potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. "	( The effect of simvastatin on the differentiation of marrow stromal cells from aging rats. Dai, K; Liu, M; Tang, T; Wang, K; Zhu, Z, 2009)	2.16
"Simvastatin is a chemical modification of lovastatin, a rate-limiting enzyme of the cholesterol synthesis pathway. "	( The use of simvastatin in bone regeneration. Park, JB, 2009)	2.19
"Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor commonly known as a cholesterol-lowering drug with additional pleiotropic effects. "	( Simvastatin improves wound strength after intestinal anastomosis in the rat. Acikgoz, S; Ankarali, H; Bahadir, B; Comert, M; Demirtas, C; Emre, AU; Irkorucu, O; Karadeniz Cakmak, G; Karakaya, K; Kertis, G; Pasaoglu, H; Tascilar, O; Ucan, BH, 2009)	3.24
"Simvastatin is a cholesterol-lowering medication heavily prescribed to treat and prevent vascular disease. "	( Recovery time in a case of gemfibrozil and simvastatin-associated rhabdomyolysis. Baker, E; Cummins, D; Mackey, M, 2009)	2.06
"Simvastatin is considered to be a promising agent for the treatment of endometriosis-associated fibrosis, which is among the major pathologies caused by endometriosis."	( Simvastatin inhibits the proliferation and the contractility of human endometriotic stromal cells: a promising agent for the treatment of endometriosis. Narahara, H; Nasu, K; Tsuno, A; Yuge, A, 2009)	2.52
"Simvastatin is a commonly prescribed, moderately potent statin. "	( Does simvastatin cause more myotoxicity compared with other statins? Backes, JM; Howard, PA; Moriarty, PM; Ruisinger, JF, 2009)	2.31
"Simvastatin (SS) is an effective cholesterol-lowering medicine, and is hydrolyzed to simvastatin acid (SSA) after oral administration. "	( High-throughput salting-out assisted liquid/liquid extraction with acetonitrile for the simultaneous determination of simvastatin and simvastatin acid in human plasma with liquid chromatography. El-Shourbagy, TA; Fan, L; Gage, E; Hautman, M; King, LL; Rodila, R; Wu, H; Zhang, J, 2010)	2.01
"Simvastatin is a hypolipemic drug with proven efficacy in the prevention of cardiovascular diseases."	( The influence of simvastatin on selected inflammatory markers in patients with chronic obstructive pulmonary disease. Dziedzina, S; Iwaniec, T; Kaczmarek, P; Rzeszutko, M; Skucha, W; Szczeklik, A; Sładek, K, 2010)	1.42
"Simvastatin (SMV) is a specific competitive inhibitor of 3-hydroxy-2-methyl-glutaryl coenzyme A reductase."	( Clinical effect of subgingivally delivered simvastatin in the treatment of patients with chronic periodontitis: a randomized clinical trial. Pradeep, AR; Thorat, MS, 2010)	1.34
"Simvastatin is a hypolipidemic drug which is used to control hypercholesterolemia and to prevent cardiovascular disease. "	( Determination of simvastatin-induced changes in bone composition and structure by Fourier transform infrared spectroscopy in rat animal model. Garip, S; Severcan, F, 2010)	2.14
"Simvastatin is a hypocholesterolemic agent presumed to cause peripheral neuropathy. "	( Microscopic and electrophysiological changes on regenerating sciatic nerves of rats treated with simvastatin. Berker, M; Daglioglu, E; Demirci, M; Karabulut, E; Tuncel, A; Tuncel, M, 2010)	2.02
"Simvastatin is a hypocholestrolemic drug that is insoluble in water. "	( Enhanced dissolution rate of simvastatin using spherical crystallization technique. Salamat, FA; Tavakoli, N; Varshosaz, J, 2011)	2.1
"Simvastatin is a cholesterol-lowering drug which inhibits 3-hydroxy-3-methylglutarylcoenzyme CoA (HMG-CoA) reductase."	( Simvastatin inhibits cell growth and induces apoptosis and G0/G1 cell cycle arrest in hepatic cancer cells. Henrich, D; Lehnert, M; Marzi, I; Meder, F; Relja, B; Wilhelm, K, 2010)	2.52
"Simvastatin is an effective lymphocyte-suppressing and anti-inflammatory agent irrespective of plasma lipid levels."	( The effect of simvastatin on lymphocyte secretory function in patients with impaired fasting glucose. Krysiak, R; Okopien, B, 2010)	1.44
"Simvastatin is a cholesterol-lowering drug that is widely used to prevent and treat atherosclerotic cardiovascular disease. "	( Simvastatin stimulates apoptosis in cholangiocarcinoma by inhibition of Rac1 activity. Dostal, DE; Glaser, SS; Guerrier, M; Meng, F; Miller, T; Munshi, MK; Priester, S; Wise, CE; Yang, F, 2011)	3.25
"Simvastatin is an effective lymphocyte-suppressing agent in mixed dyslipidemic patients but not in IGT patients."	( Lymphocyte-suppressing effect of simvastatin in mixed dyslipidemic patients but not impaired glucose tolerance patients. Krysiak, R; Okopień, B, 2011)	1.37
"Simvastatin is a competitive inhibitor of 3-hydroxymethylglutaryl coenzyme A reductase activity, whereas geraniol is a monoterpene with multiple pharmacologic effects on mevalonate metabolism. "	( Geraniol and simvastatin show a synergistic effect on a human hepatocarcinoma cell line. Crespo, R; de Bravo, MG; Polo, MP, 2011)	2.18
"Simvastatin is a hydrophobic statin that enters cells by other mechanisms."	( Differential effects of pravastatin and simvastatin on the growth of tumor cells from different organ sites. Chakraborty, K; Harirforoosh, S; Hsi, L; Krishnan, K; Menter, DG; Newman, RA; Ramsauer, VP; Yang, P, 2011)	1.36
"Simvastatin (SMV) is a specific competitive inhibitor of 3-hydroxy-2-methyl-glutaryl coenzyme A reductase. "	( Efficacy of subgingivally delivered simvastatin in the treatment of patients with type 2 diabetes and chronic periodontitis: a randomized double-masked controlled clinical trial. Bajaj, P; Kumari, M; Pradeep, AR; Rao, NS, 2013)	2.11
"Simvastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, which has been shown to ameliorate the development of pulmonary hypertension in animal model by suppression of pulmonary artery smooth muscle cells (PASMCs) proliferation, yet its underlying molecular mechanisms are not completely understood. "	( Statins inhibit pulmonary artery smooth muscle cell proliferation by upregulation of HO-1 and p21WAF1. Han, D; Li, M; Li, S; Liu, Y; Lu, J; Shi, H; Wang, G; Wu, Y; Xie, X; Xu, J; Zhang, D; Zhang, Y, 2012)	1.82
"For simvastatin, solubility is a crucial rate limiting factor to achieve its desired level in systemic circulation for pharmacological response."	( Solubility enhancement of simvastatin: a review. Murtaza, G, )	0.91
"Simvastatin is a substrate of CYP3A4 enzyme."	( Paracetamol and simvastatin: a potential interaction resulting in hepatotoxicity. Gumbrevičius, G; Stankevičius, E; Sveikata, A; Sveikatienė, R, 2012)	1.45
"Simvastatin is a cholesterol-lowering drug whose pleiotropic effects may have a therapeutic impact on bone. "	( Protective mechanisms of simvastatin in experimental periodontal disease. Brito, GA; Dalcico, R; de Menezes, AM; Deocleciano, OB; Oriá, RB; Ribeiro, RA; Vale, ML, 2013)	2.14
"Simvastatin is an effective hypolipemic agent."	( [Simvastatin and extrinsic coagulation pathway in peritoneally dialyzed patients]. Hryszko, T; Małyszko, J; Małyszko, JS; Myśliwiec, M; Pawlak, K, 2002)	1.95
"Simvastatin is a competitive inhibitor of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase which is effective in the treatment of various hyperlipidemia. "	( [Simvastatin-induced lichen planus pemphigoides]. Durand, L; Ligeron, C; Meunier, L; Meynadier, J; Michot, C; Stoebner, PE, 2003)	2.67
"simvastatin is an effective oral antilipemic agent for treating Thai patients with hypercholesterolemia. "	( Oral simvastatin as an antilipemic therapy: effect on creatine kinase in hypercholesterolemic subjects. Assawawitoontip, S; Wiwanitkit, V, 2003)	2.28
"Simvastatin is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-determining enzyme for cholesterol synthesis which is used in the treatment of hypercholesterolemias, particularly in type IIa and IIb hyperlipoproteinemias, frequently in postmenopausal women. "	( Effects of simvastatin on the development of osteopenia caused by ovariectomy in rats. Gubała, I; Janiec, W; Misiarz-Myrta, M; Pytlik, M, )	1.96
"Simvastatin is an effective hypolipemic agent in CAPD patients. "	( Influence of simvastatin on aspects of thrombogenesis in CAPD patients. Hryszko, T; Malyszko, J; Malyszko, JS; Mysliwiec, M, )	1.94
"Simvastatin is a hydroxymethyl glutaryl coenzyme A reductase inhibitor commonly used to treat patients with hyperlipidemia. "	( Rhabdomyolysis associated with simvastatin-nefazodone therapy. Monaghan, MS; Skrabal, MZ; Stading, JA, 2003)	2.05
"Simvastatin is a component of the Heart Health Programme, which also addresses other modifiable risk factors such as diet, exercise, and smoking."	( Reclassification of simvastatin to over-the-counter status in the United Kingdom: a primary prevention strategy. Nash, DB; Nash, SA, 2004)	1.37
"Simvastatin is a long-established hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, first introduced in 1988. "	( Simvastatin: a review. Pedersen, TR; Tobert, JA, 2004)	3.21
"Simvastatin is an HMG-CoA reductase inhibitor responsible for many clinical benefits."	( The changes in the endothelial expression of cell adhesion molecules and iNOS in the vessel wall after the short-term administration of simvastatin in rabbit model of atherosclerosis. Kopecky, M; Nachtigal, P; Semecky, V; Solichova, D; Zdansky, P, 2005)	1.25
"Simvastatin is an HMG-CoA reductase inhibitor that is metabolized by the cytochrome P450 (CYP) 3A4."	( Interaction between amlodipine and simvastatin in patients with hypercholesterolemia and hypertension. Hayashi, H; Kosuge, K; Nishio, S; Ohashi, K; Uchida, S; Watanabe, H, 2005)	1.33
"Simvastatin therapy seems to be a cost-effective and useful method for lymphocyte cross-match-positive kidney transplantation candidates compared with immunoadsorption or intravenous immunoglobulin use."	( Simvastatin therapy in lymphocyte cross-match-positive kidney transplantation candidates. Demirbas, A; Dinckan, A; Gurkan, A; Karatas, GU; Kececioglu, N; Kocak, H; Tuncer, M; Yakupoglu, U; Yakupoglu, YK; Yegin, O, 2005)	3.21
"Simvastatin is a powerful inhibitor of type I collagen gene expression in normal and systemic sclerosis fibroblasts. "	( Inhibition of systemic sclerosis dermal fibroblast type I collagen production and gene expression by simvastatin. Fertala, J; Huaman, G; Jiménez, SA; Louneva, N, 2006)	1.99
"Simvastatin is a semisynthetic derivative of the fungal polyketide lovastatin and is an important drug for lowering cholesterol levels in adults. "	( Efficient synthesis of simvastatin by use of whole-cell biocatalysis. Tang, Y; Xie, X, 2007)	2.09
"Simvastatin (SIM) is a commonly prescribed statin with anti-inflammatory and antioxidant properties."	( Gastric antisecretory and antiulcer effects of simvastatin in rats. Al Moutaery, M; Al Rayes, H; Al Swailam, R; Arshaduddin, M; Elfaki, I; Khan, HA; Tariq, M, 2007)	1.32
"Simvastatin is an important cholesterol lowering compound and is currently synthesized from the natural product lovastatin via multistep chemical synthesis. "	( Improving simvastatin bioconversion in Escherichia coli by deletion of bioH. Tang, Y; Wong, WW; Xie, X, 2007)	2.18
"Simvastatin is a promising candidate of a novel medical treatment for the prevention of CA progression."	( Simvastatin suppresses the progression of experimentally induced cerebral aneurysms in rats. Aoki, T; Hashimoto, N; Ishibashi, R; Kataoka, H; Nozaki, K, 2008)	2.51
"Simvastatin is an agent of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor group of drugs. "	( Simvastatin: two decades in a circle. Cokkinos, DV; Ioannis, V; Katerina, A; Kolovou, GD, 2008)	3.23
"Simvastatin proves to be a safe and effective lipid-lowering drug during long-term treatment."	( Long-term experience (6 years) with simvastatin in patients with heterozygous familial hypercholesterolaemia. Knops, RE; Kroon, AA; Mol, MJ; Stalenhoef, AF; Stuyt, PM, 1995)	2.01
"Simvastatin is a hypolipidaemic agent, a statin which inhibits cellular cholesterol synthesis by blocking 3HMG CoA reductase. "	( [Monitoring plasma levels of vitamin D metabolites in simvastatin (Zocor) therapy in patients with familial hypercholesterolemia]. Ceska, R; Justová, V; Jůzová, Z; Kvasilová, M; Procházková, R; Sobra, J; Wilczek, H, 1994)	1.98
"Simvastatin is an inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, the key enzyme in the synthesis of cholesterol, recently introduced in the therapy of hypercholesterolemic patients. "	( Effects of long-term simvastatin treatment on testicular and adrenal steroidogenesis in hypercholesterolemic patients. Argenio, GF; Bernini, GP; Franchi, F; Gasperi, M; Salvetti, A; Vivaldi, MS, 1994)	2.05
"Simvastatin is a safe, effective therapy for hypercholesterolemia in proteinuric states."	( Simvastatin therapy for hypercholesterolemic patients with nephrotic syndrome or significant proteinuria. Harris, KP; Hattersley, JM; Moorhead, JF; Ramaswamy, C; Thomas, ME; Varghese, Z; Walls, J; Wheeler, DC; Williams, JD, 1993)	2.45
"Simvastatin is a methyl analogue of lovastatin and acts as an HMG-CoA reductase inhibitor effective in the treatment of hypercholesterolaemia. "	( Clinical pharmacokinetics and practical applications of simvastatin. Mauro, VF, 1993)	1.97
"Simvastatin seems to be an effective and relatively well-tolerated drug for dyslipemias in CAPD."	( The effect of simvastatin on dyslipemia in continuous ambulatory peritoneal dialysis patients. Antoniou, S; Dimitriadis, A; Hatzisavvas, N; Kaldi, I; Pastore, F; Stangou, M, 1993)	1.37
"Simvastatin is an HMG-CoA reductase inhibitor used in the treatment of patients with hypercholesterolaemia. "	( Simvastatin. A reappraisal of its pharmacology and therapeutic efficacy in hypercholesterolaemia. McTavish, D; Plosker, GL, 1995)	3.18
"Simvastatin is a very effective hypocholesterolemic drug which, reducing cholesterol biosynthesis, can affect normal steroid hormone production. "	( Testicular function in hypercholesterolemic male patients during prolonged simvastatin treatment. Azzarito, C; Boiardi, L; Portioli, I; Vergoni, W; Zini, M, 1996)	1.97
"Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and also selectively inhibits the growth of leukaemic progenitor cells. "	( A comparison of the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors simvastatin, lovastatin and pravastatin on leukaemic and normal bone marrow progenitors. Catovsky, D; Clutterbuck, RD; Millar, JL; Newman, A; Powles, RL, 1997)	1.95
"Simvastatin is a potent inhibitor of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase intended for use as a hypocholesterolemic agent. "	( Rhabdomyolysis associated with simvastatin-gemfibrozil therapy. Isley, W; Rajeshawari, M; Tal, A, 1997)	2.03
"Simvastatin (SV) is a lactone prodrug used for the treatment of hypercholesterolemia. "	( In vitro metabolism of simvastatin in humans [SBT]identification of metabolizing enzymes and effect of the drug on hepatic P450s. Arison, BH; Gorham, LM; Liu, L; Ma, B; Prueksaritanont, T; Slaughter, DE; Vyas, KP; Yu, X; Zhao, JJ, 1997)	2.05
"Simvastatin is a cholesterol-lowering agent that is metabolized through CYP3A4. "	( Grapefruit juice-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Kivistö, KT; Lilja, JJ; Neuvonen, PJ, 1998)	2.08
"Simvastatin is a substrate for cytochrome P450 3A4 (CYP3A4)."	( Concomitant use of cytochrome P450 3A4 inhibitors and simvastatin. Dobrinska, MR; Gruer, PJ; Mercuri, MF; Tobert, JA; Vega, JM, 1999)	1.27
"Simvastatin is an inhibitor of HMG-CoA reductase used in the treatment of hypercholesterolemia. "	( Endothelium modulates contractile response to simvastatin in rat aorta. Alvarez de Sotomayor, M; Herrera, MD; Marhuenda, E; Pérez-Guerrero, C, )	1.83
"Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase that is used as a cholesterol-lowering agent and is metabolized by cytochrome P450 3A (CYP3A) enzymes. "	( The interaction of diltiazem with simvastatin. Brater, DC; Hall, SD; Mousa, O; Sunblad, KJ, 2000)	2.03
"Simvastatin is a highly effective cholesterol-lowering drug with a beneficial effect on the entire lipid spectrum in a cross-section of Asian patients, and is well tolerated."	( A randomised comparison of simvastatin versus simvastatin and low cholesterol diet in the treatment of hypercholesterolaemia. Chong, KS; Pasamanikam, K; Tan, KH; Thuraisingham, S; Yap, SF, 2000)	1.33
"Simvastatin is a safe and efficacious lipid-lowering drug."	( Lipid-lowering effect of simvastatin in patients of type 2 diabetes mellitus. Goyal, RK; Udawat, H, )	1.16
"Simvastatin is an effective hypolipemic agent and favorably affects platelet aggregation, endothelial function and fibrinolysis in CAPD patients."	( Effects of long-term treatment with simvastatin on some hemostatic parameters in continuous ambulatory peritoneal dialysis patients. Hryszko, T; Małyszko, J; Małyszko, JS; Myśliwiec, M, )	1.85
"Simvastatin appears to be a safe and effective treatme"	( Safety and efficacy of simvastatin in hypercholesterolemic patients undergoing chronic renal dialysis. Morgan, C; Rigby, RJ; Saltissi, D; Westhuyzen, J, 2002)	1.35
"Simvastatin is an effective hypocholesterolemic drug that inhibits cholesterol synthesis selectively in the liver, but could have potential side effects on the adrenal gland, ovary, and testis, as these three glands use cholesterol for their hormonal biosynthesis. "	( Long-term therapy with high-dose simvastatin does not affect adrenocortical and gonadal hormones in hypercholesterolemic patients. Agosti, A; Azzarito, C; Biagi, R; Boiardi, L; Dotti, C; Portioli, I; Zini, M, 1992)	2.01
"Simvastatin is a pharmacological molecule belonging to the family of HMG-CoA reductase inhibitors, recently included in plasma cholesterol lowering therapy. "	( [Dyslipidemia in the uremic patient: the therapeutic role played by simvastatin]. Angelé, B; Bellinghieri, G; Savica, V, 1992)	1.96
"Simvastatin is an effective, well tolerated lipid lowering drug, without significant attenuation of effect with prolonged use. "	( Treatment of primary hypercholesterolaemia with simvastatin. New Zealand multicentre evaluation. Charleson, H; French, JK; Lewis, GR; Lintott, CJ; Maling, TJ; Nye, ER; Reuben, S; Scott, RS; Sharpe, DN; White, HD, 1991)	1.98
"Simvastatin (SV) is a lactone prodrug which undergoes reversible metabolism."	( Metabolic disposition studies on simvastatin, a cholesterol-lowering prodrug. Chen, IW; Duggan, DE; Duncan, CA; Rosegay, A; Vickers, S, )	1.13
"Simvastatin is a potent competitive inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) which is the rate-limiting enzyme of cholesterol synthesis. "	( Biochemical changes and morphological alterations of the liver in guinea-pigs after administration of simvastatin (HMG CoA reductase-inhibitor). Desager, JP; Harvengt, C; Horsmans, Y, 1990)	1.94
"Simvastatin appears to be an important asset in the treatment of hypercholesterolaemia."	( The effects of simvastatin on serum lipoproteins in severe hypercholesterolaemia. Demacker, PN; Mol, MJ; Stalenhoef, AF; Stuyt, PM, 1990)	1.35
"Simvastatin is an effective cholesterol lowering agent in older patients."	( The use of simvastatin, an HMG CoA reductase inhibitor, in older patients with hypercholesterolemia and atherosclerosis. Bach, LA; Cooper, ME; Jerums, G; O'Brien, RC, 1990)	1.39
"Simvastatin appears to be a well-tolerated and effective new agent used once-a-day as an adjunct to diet in the management of patients with hypercholesterolemia."	( Effects of simvastatin and probucol in hypercholesterolemia (Simvastatin Multicenter Study Group II). Alexander, S; Cook, TJ; Mantell, G; Pietro, DA; Staggers, JE, 1989)	1.39
"Simvastatin appeared also to be a potent hypolipidemic drug in 10 patients with familial dysbetalipoproteinemia."	( Efficacy and tolerability of simvastatin (MK-733). Mol, MJ; Stalenhoef, AF; Stuyt, PM, 1989)	1.29
"Simvastatin appears to be an effective and well-tolerated agent for the treatment of primary hypercholesterolemia and, as further study confirms long-term safety and efficacy, it should become a useful addition to the therapeutic armamentarium."	( Simvastatin: the clinical profile. Walker, JF, 1989)	2.44
"Simvastatin seems to be an effective and safe drug as monotherapy in the treatment of heterozygous familial hypercholesterolemia."	( Simvastatin (MK 733) in heterozygous familial hypercholesterolemia: a two-year trial. Harvengt, C; Leclercq, V, 1989)	2.44
"Simvastatin appears to be an important asset in the treatment of hypercholesterolaemia."	( [Efficacy and safety of simvastatin, a new cholesterol-lowering drug]. Mol, MJ; Stalenhoef, AF; Stuyt, PM, 1989)	1.31

Effects

Simvastatin has a potent cytotoxic effect resulting in the death of human breast cancer MCF-7 and MDA-MB-231 cell lines, demonstrating its potential as a new candidate for cancer drug. It has a cardioprotective effects against LPS induced apoptosis.

Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. It has been reported to exhibit anti-tumor activity in a variety of cancers; but its roles and molecular mechanisms in RCC remain unclear.

Excerpt	Reference	Relevance
"Simvastatin has a potent cytotoxic effect resulting in the death of human breast cancer MCF-7 and MDA-MB-231 cell lines, demonstrating its potential as a new candidate for cancer drug. ."	( Cytotoxicity of Simvastatin in Human Breast Cancer MCF-7 and MDA-MB-231 Cell Lines. Gunawan, T; Rangkuti, AR; Rezano, A; Ridhayanti, F; Wijaya, I; Winarno, GNA, 2021)	2.41
"Simvastatin has a protective effect on myocardial depression caused by sepsis."	( An experimental study of the protective effect of simvastatin on sepsis-induced myocardial depression in rats. Wang, Y; Yang, W; Zhang, L; Zhang, R; Zhao, X, 2017)	1.43
"Simvastatin has an additional pleiotropic effect halting inflammation and decreasing fibrosis due to increasing IL-10 leading to a hepatoprotective effect."	( Simvastatin exerts antifibrotic effect and potentiates the antischistosomal effects of praziquantel in a murine model: Role of IL10. Aboulfotouh, N; Aladeeb, NM; Elkaref, A; Elmasry, A, 2017)	2.62
"Simvastatin has a cardioprotective effects against LPS induced apoptosis."	( Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression. Amidžić, L; Gajanin, R; Jaćević, V; Kuča, K; Nežić, L; Škrbić, R, 2018)	2.64
"Simvastatin has a protective effect against acute pancreatitis."	( Acute pancreatitis. Talukdar, R; Vege, SS, 2015)	1.14
"Simvastatin has a suppressing effect on LPS-induced inflammatory cytokine, cell adhesion molecules and NF-κB transcription factors in HDPCs. "	( Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells. Choi, CH; Hwang, YC; Jung, JY; Kim, WJ; Koh, JT; Lee, BN; Lee, KJ; Min, KS; Nör, JE; Woo, SM, 2017)	3.34
"Simvastatin may has a potential therapeutic target in diabetic nephropathy, which may be partly attributed to down-regulating over-expression of MMP-9 in renal tissue."	( Simvastatin protects diabetic rats against kidney injury through the suppression of renal matrix metalloproteinase-9 expression. Chen, K; Chen, Y; Li, XC; Wang, YX; Yang, GW; Yao, XM; Ye, SD; Zai, Z, 2010)	3.25
"Simvastatin has an inhibitory effect on the differentiation and maturation of DC, and selectively reduce the T-cell proliferation induced by DC from patients with ON."	( Increased immunopotency of monocyte derived dendritic cells from patients with optic neuritis is inhibited in vitro by simvastatin. Frederiksen, J; Svane, IM; Tsakiri, A; Tsiantoulas, D, 2010)	1.29
"Simvastatin has a dual effect on tumorigenesis. "	( HMG-CoA reductase inhibition causes increased necrosis and apoptosis in an in vivo mouse glioblastoma multiforme model. Bababeygy, SR; Hou, LC; Polevaya, NV; Prugpichailers, T; Steinman, L; Sun, A; Tse, V; Veeravagu, A; Xiong, A; Youssef, S, 2009)	1.8
"Simvastatin has a preventive effect on rat PH, it inhibits mast cell proliferation may be one of mechanism."	( [The change of mast cells and macrophages in the lung of rat with pulmonary hypertension]. Dou, H; Li, P; Su, J; Zhang, T; Zhao, L; Zhao, Y; Zhou, TF, 2006)	1.06
"Simvastatin has a strong anti-inflammatory effect on HPBM cells including upregulation of the atheroprotective factor KLF-2. "	( Simvastatin has an anti-inflammatory effect on macrophages via upregulation of an atheroprotective transcription factor, Kruppel-like factor 2. Häkkinen, SK; Horrevoets, AJ; Kansanen, E; Levonen, AL; Lumivuori, H; Tuomisto, TT; Turunen, MP; van Thienen, JV; Ylä-Herttuala, S, 2008)	3.23
"Simvastatin also has a preventive effect on the progression of preexisting CAs."	( Simvastatin suppresses the progression of experimentally induced cerebral aneurysms in rats. Aoki, T; Hashimoto, N; Ishibashi, R; Kataoka, H; Nozaki, K, 2008)	2.51
"Simvastatin has a beneficial effect on abnormal lipid levels in SRNS but the effectiveness of long-term therapy needs to be evaluated."	( Hyperlipidaemia, diet and simvastatin therapy in steroid-resistant nephrotic syndrome of childhood. Coleman, JE; Watson, AR, 1996)	1.32
"Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive."	( Simvastatin Blocks Reinstatement of Cocaine-induced Conditioned Place Preference in Male Mice with Brain Lipidome Remodeling. Cen, X; Dai, Y; He, Y; Jiang, L; Li, H; Li, M; Liu, H; Wan, X; Wang, Y; Xu, R; Xu, W; Zhang, H; Zhang, J; Zhao, Y, 2021)	2.79
"Simvastatin has previously been associated with drug-induced interstitial lung disease. "	( Role of Drug-Gene Interactions and Pharmacogenetics in Simvastatin-Associated Pulmonary Toxicity. Bast, A; Bekers, O; Drent, M; Harmsze, AM; Jessurun, NT; van Puijenbroek, EP; Wijnen, PA, 2021)	2.31
"Simvastatin has been shown to be cardioprotective by decreasing matrix metalloproteinases' (MMPs) activity."	( HMG-CoA Reductase Inhibitor, Simvastatin Is Effective in Decreasing Degree of Myocarditis by Inhibiting Metalloproteinases Activation. Haczkiewicz-Leśniak, K; Kwiatkowska, J; Piasecki, T; Podhorska-Okołów, M; Sapa-Wojciechowska, A; Skrzypiec-Spring, M; Szeląg, A, 2021)	1.63
"Simvastatin has potential anti-thrombotic effects on liver endothelial cells."	( Simvastatin Prevents Liver Microthrombosis and Sepsis Induced Coagulopathy in a Rat Model of Endotoxemia. Arnaboldi, F; Bitto, N; Colombo, M; Denti, L; Dondossola, D; Gagliano, N; La Mura, V; Latini, R; Liguori, E; Peyvandi, F; Procacci, P; Ristagno, G; Salerno, F; Sartori, P; Tripodi, A, 2022)	2.89
"Simvastatin has been tested as vasoprotective drug in experimental models of CLD showing promising results, but also limiting adverse effects."	( Simvastatin-loaded polymeric micelles are more effective and less toxic than conventional statins in a pre-clinical model of advanced chronic liver disease. Andrade, F; Augustin, S; Barberá, A; Bravo, M; Genescà, J; Gil, M; Gracia-Sancho, J; Hide, D; Martell, M; Rafael, D; Raurell, I; Schwartz, S; Vargas, V, 2020)	2.72
"Simvastatin has attracted considerable attention since the discovery of its pharmacological effects on different pathogenic processes, including inflammation."	( Simvastatin abolishes nitric oxide- and reactive oxygen species-induced cyclooxygenase-2 expression by blocking the nuclear factor κB pathway in rabbit articular chondrocytes. Han, Y; Kim, SJ; Yu, SM, 2020)	2.72
"Simvastatin (SIM) has been documented to induce the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). "	( A simvastatin-releasing scaffold with periodontal ligament stem cell sheets for periodontal regeneration. Chen, J; Deng, J; Li, Q; Zhao, B; Zhao, L, )	2.3
"Simvastatin has been reported to exhibit anti-tumor activity in a variety of cancers; however, its roles and molecular mechanisms in RCC remain unclear."	( Simvastatin suppresses renal cell carcinoma cells by regulating DDX5/DUSP5. Jin, C; Liu, W; Qiu, Y; Wang, H; Xu, W; Zhao, Y, 2021)	2.79
"Simvastatin has a potent cytotoxic effect resulting in the death of human breast cancer MCF-7 and MDA-MB-231 cell lines, demonstrating its potential as a new candidate for cancer drug. ."	( Cytotoxicity of Simvastatin in Human Breast Cancer MCF-7 and MDA-MB-231 Cell Lines. Gunawan, T; Rangkuti, AR; Rezano, A; Ridhayanti, F; Wijaya, I; Winarno, GNA, 2021)	2.41
"Simvastatin has been touted as a potential neuroprotective agent for neurologic disorders such as PD, but the specific underlying mechanism remains unclear."	( Simvastatin Prevents Neurodegeneration in the MPTP Mouse Model of Parkinson's Disease via Inhibition of A1 Reactive Astrocytes. Bu, WG; Du, RW, 2021)	2.79
"Simvastatin has been determined efficiently by the developed method either alone or in mixture with lovastatin giving LOQ values of 0.009 and 0.02% w/w, respectively indicating good sensitivity."	( FTIR spectroscopic study of two isostructural statins: Simvastatin and Lovastatin as authentic and in pharmaceuticals. Abdel Hakiem, AF; Ali, HRH; Mohamed, NA, 2021)	1.59
"Simvastatin has a protective effect on myocardial depression caused by sepsis."	( An experimental study of the protective effect of simvastatin on sepsis-induced myocardial depression in rats. Wang, Y; Yang, W; Zhang, L; Zhang, R; Zhao, X, 2017)	1.43
"Simvastatin has an additional pleiotropic effect halting inflammation and decreasing fibrosis due to increasing IL-10 leading to a hepatoprotective effect."	( Simvastatin exerts antifibrotic effect and potentiates the antischistosomal effects of praziquantel in a murine model: Role of IL10. Aboulfotouh, N; Aladeeb, NM; Elkaref, A; Elmasry, A, 2017)	2.62
"Simvastatin has been reported to reduce cardiovascular related morbidity and mortality in clinical trials which was independent of its cholesterol-lowering effect. "	( Protective Effect and Potential Mechanism of Simvastatin on Myocardial Injury Induced by Diabetes with Hypoglycemia. Chen, H; Cui, X; Li, H; Liu, R; Yang, L; Zhao, Q, 2018)	2.18
"Simvastatin has protective effect on myocardial injury caused by diabetes with hypoglycemia, which is associated with increased calcium sensitivity, decreased NF-κB expression and altered miRNA expression profile."	( Protective Effect and Potential Mechanism of Simvastatin on Myocardial Injury Induced by Diabetes with Hypoglycemia. Chen, H; Cui, X; Li, H; Liu, R; Yang, L; Zhao, Q, 2018)	2.18
"Simvastatin has been applied to improve and accelerate the osseointegration of implants by increasing the quantity and quality of bone tissue."	( Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity. Cheng, J; Fu, Y; Gu, Q; Jiang, H; Shi, G; Xu, L; Xu, R; Zhang, P, 2018)	2.64
"simvastatin has been demonstrated to exhibit antitumor effects, and so the aim of the present study was to assess the effects of simvastatin on the growth of human PTEN haploinsufficient lipoma cells."	( Simvastatin induces apoptosis in PTEN‑haploinsufficient lipoma cells. Garten, A; Händel, N; Kässner, F; Kiess, W; Körner, A; Landgraf, K; Penke, M; Richter, S; Sauer, T, 2018)	2.64
"Simvastatin has been reported to be associated with neuroprotective effect after spinal cord ischemia-reperfusion (IR) injury."	( The attenuation of neurological injury from the use of simvastatin after spinal cord ischemia-reperfusion injury in rats. Han, SH; Hwang, JY; Kim, JH; Park, JW; Park, SJ; Ryu, JH; Sohn, HM, 2018)	1.45
"Simvastatin has been reported to promote osteoblastic activity, inhibit osteoclastic activity, and support osteoblast differentiation induced by bone morphogenetic protein. "	( Evaluation of the Efficacy of Simvastatin in Bone Regeneration after Surgical Removal of Bilaterally Impacted Third Molars-A Split-Mouth Randomized Clinical Trial. Bathija, NA; Degala, S, 2018)	2.21
"Simvastatin has recently been demonstrated to serve a potential role in the prophylaxis and therapeutics of a number of human cancers."	( Effect of survivin downregulation by simvastatin on the growth and invasion of salivary adenoid cystic carcinoma. Cai, WY; Li, T; Song, WT; Sun, JH; Yan, F; Zhuang, Y, 2018)	1.48
"Simvastatin has different effects on the proliferation, apoptosis and protein expressions of KFs in a dosedependent manner under different conditions. "	( [Different effects of simvastatin on keloid fibroblasts under hypoxia and TGF-β1 treatment]. An, Y; Chen, B; Kang, C; Qin, Z; Yu, D; Zhao, X, 2016)	2.19
"Simvastatin has a cardioprotective effects against LPS induced apoptosis."	( Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression. Amidžić, L; Gajanin, R; Jaćević, V; Kuča, K; Nežić, L; Škrbić, R, 2018)	2.64
"simvastatin has pleiotropic anti-inflammatory and immunomodulatory effects potentially usefull to prevent chemotherapy-induced gastrointestinal mucositis. "	( Effects of simvastatin on 5-fluorouracil-induced gastrointestinal mucositis in rats. Araújo Filho, I; Azevedo, ÍM; Lima, ML; Medeiros, ADC; Moreira, MD, 2018)	2.31
"Simvastatin therapy has beneficial effects on inflammatory markers in plasma, but CoQ10 supplementation seems to have no additional potentiating effect in patients in primary prevention. "	( Inflammatory biomarkers in patients in Simvastatin treatment: No effect of co-enzyme Q10 supplementation. Chrøis, KM; Dela, F; Dohlmann, TL; Hansen, M; Helge, JW; Kelly, B; Kuhlman, ACB; Larsen, S; Morville, T; Sahl, RE, 2019)	2.23
"Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. "	( A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients. Ahn, JB; Han, SW; Kang, WK; Kim, ST; Kim, TW; Kim, Y; Lee, J; Lim, HY; Park, JO; Park, YS, 2019)	2.24
"Simvastatin has previously been found to be a potential degenerative disc disease treatment."	( Multiple-Exposure Drug Release from Stable Nanodroplets by High-Intensity Focused Ultrasound for a Potential Degenerative Disc Disease Treatment. C Park, Y; Haworth, K; Lin, CY; Mahoney, E; Mercado-Shekhar, KP; Nguyen, K; Pan, HY; Zhang, Z, 2019)	1.24
"Simvastatin has been reported to increase the therapeutic effects of many kinds of stem cells by increasing the number of those cells. "	( The effects of simvastatin on cellular viability, stemness and osteogenic differentiation using 3-dimensional cultures of stem cells and osteoblast-like cells. Lee, H; Na, CB; Park, JB, 2019)	2.31
"Simvastatin has recently been demonstrated to serve as a therapeutic agent for osteoporosis. "	( Preparation of calcium phosphate nanocapsules including simvastatin/deoxycholic acid assembly, and their therapeutic effect in osteoporosis model mice. Ito, T; Makino, K; Otsuka, M; Takemasa, M, 2013)	2.08
"Simvastatin has been shown to stimulate osteogenic cell differentiation. "	( Simvastatin enhances human osteoblast proliferation involved in mitochondrial energy generation. Chang, JK; Chuang, SC; Ho, ML; Li, CJ; Liao, HJ; Wang, GJ, 2013)	3.28
"Simvastatin has inhibitory effects on cancers. "	( Simvastatin enhances the chemotherapeutic efficacy of S-1 against bile duct cancer: E2F-1/TS downregulation might be the mechanism. Cai, JP; Chen, W; Hao, XY; Hou, X; Liang, LJ; Yin, XY, 2013)	3.28
"Simvastatin has low aqueous solubility resulting in low oral bioavailability (5%) and thus presents a challenge in formulating a suitable dosage form. "	( Preparation and characterization of Simvastatin solid dispersion using skimmed milk. Banerjee, SK; Behera, AL; Gaikwad, DD; Harer, SL; Sonar, PA, 2015)	2.13
"Simvastatin has important immune-modulatory and anti-inflammatory effects independent of lipid lowering effects. "	( Effect of simvastatin on inflammatory cytokines balance in air pouch granuloma model. Al-Gayyar, MM; El-Gayar, AM; Hassan, HM; Ibrahim, TM, 2014)	2.25
"Simvastatin has shown potential wound-healing properties; however, no studies have investigated its use in venous ulcers."	( Simvastatin as a novel therapeutic agent for venous ulcers: a randomized, double-blind, placebo-controlled trial. Casintahan, MF; Evangelista, MT; Villafuerte, LL, 2014)	2.57
"Simvastatin has been shown to possess potent anti-inflammatory properties."	( Simvastatin reduces burn injury-induced splenic apoptosis via downregulation of the TNF-α/NF-κB pathway. Bonab, AA; Fischman, AJ; Kaneki, M; Tompkins, RG; Yu, YM; Zhao, G, 2015)	2.58
"Simvastatin has protective effects on retinal ischemia reperfusion injury, and the mechanism is closely related to inhibiting retinal cell apoptosis by adjusting the express of Bcl-2 and Bax."	( [Effect of simvastatin on retinal Bcl-2/Bax expression and cell apoptosis in rats with ischemia-reperfusion injury]. Yan, H; Zhang, Y, 2014)	2.23
"Simvastatin has been shown to prevent the development of pulmonary hypertension (PH) in experimental models of PH."	( Prevention of pulmonary hypoplasia and pulmonary vascular remodeling by antenatal simvastatin treatment in nitrofen-induced congenital diaphragmatic hernia. Da Costa, AM; de Medina, G; Dewachter, C; Dewachter, L; Hupkens, E; Makanga, M; Maruyama, H; Naeije, R, 2015)	1.36
"Simvastatin has anti-inflammatory actions, including improvement of endothelial function, by inducing a novel pro-resolving lipid, the 5-lypoxygenase derivative 15-epi-lipoxin A4 (15-epi-LXA4), which belongs to aspirin-triggered lipoxins."	( Simvastatin and Benznidazole-Mediated Prevention of Trypanosoma cruzi-Induced Endothelial Activation: Role of 15-epi-lipoxin A4 in the Action of Simvastatin. Campos-Estrada, C; Ferreira, J; González-Herrera, F; Kemmerling, U; Lapier, M; Liempi, A; López-Muñoz, R; Maya, JD; Pesce, B, 2015)	2.58
"Simvastatin has pleiotropic properties; it penetrates the brain and, as well as reducing cholesterol, reduces inflammation when used at clinically relevant doses over the short term."	( Evaluating early administration of the hydroxymethylglutaryl-CoA reductase inhibitor simvastatin in the prevention and treatment of delirium in critically ill ventilated patients (MoDUS trial): study protocol for a randomized controlled trial. Agus, A; Alce, TM; Casarin, A; Ely, EW; Jackson, JC; McAuley, DF; McDowell, C; Murphy, L; Page, VJ; Zhao, X, 2015)	1.36
"Simvastatin has been shown to protect from renal IRI in several experimental studies."	( Intensive perioperative simvastatin treatment protects from chronic kidney allograft injury. Koskinen, PK; Palin, NK; Rintala, JM; Savikko, J, 2015)	1.45
"Simvastatin has a protective effect against acute pancreatitis."	( Acute pancreatitis. Talukdar, R; Vege, SS, 2015)	1.14
"Simvastatin (SV) has been reported to improve cognitive deficits in Alzheimer's disease. "	( Simvastatin Enhances Spatial Memory and Long-Term Potentiation in Hippocampal CA1 via Upregulation of α7 Nicotinic Acetylcholine Receptor. Chen, L; Chen, T; Sha, S; Wang, C; Zhou, L, 2016)	3.32
"Simvastatin has been recently demonstrated to have a neuroprotective effect in nervous system diseases."	( Neuroprotective Effect of Simvastatin via Inducing the Autophagy on Spinal Cord Injury in the Rat Model. Bi, J; Gao, K; Han, D; Li, H; Mei, X; Wan, Z; Wang, G; Wang, Y; Yao, T; Yuan, Y, 2015)	1.44
"Simvastatin (SV) has been reported to improve dementia and slow progression of Alzheimer's disease (AD), however there are conflicting reports."	( Dose-Dependent Neuroprotection and Neurotoxicity of Simvastatin through Reduction of Farnesyl Pyrophosphate in Mice Treated with Intracerebroventricular Injection of Aβ 1-42. Cao, X; Chen, L; Chen, T; Jin, H; Li, G; Sha, S; Wan, Q; Wang, C; Zhang, B, 2016)	2.13
"Simvastatin (SV) has been demonstrated to exert excellent anabolic effects on bone."	( In vivo evaluation of a simvastatin-loaded nanostructured lipid carrier for bone tissue regeneration. Lai, C; Niu, M; Wang, C; Wang, Z; Wu, W; Yue, X; Zhang, Q; Zhang, T; Zhou, L, 2016)	1.46
"Simvastatin has a suppressing effect on LPS-induced inflammatory cytokine, cell adhesion molecules and NF-κB transcription factors in HDPCs. "	( Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells. Choi, CH; Hwang, YC; Jung, JY; Kim, WJ; Koh, JT; Lee, BN; Lee, KJ; Min, KS; Nör, JE; Woo, SM, 2017)	3.34
"Simvastatin has anti-inflammatory effects that could be of interest for asthma therapy."	( Simvastatin requires activation in accessory cells to modulate T-cell responses in asthma and COPD. Bendella, Z; Boyaci, N; Gallert, WJ; Grensemann, B; Jungck, D; Knobloch, J; Koch, A; Körber, S; Yakin, Y; Yanik, SD, 2016)	2.6
"Simvastatin has lung vascular-protective effects via augmentation of endothelial barrier function. "	( Simvastatin Attenuates Acute Lung Injury via Regulating CDC42-PAK4 and Endothelial Microparticles. Gao, C; Jing, L; Yu, Y; Zhang, X, 2017)	3.34
"Simvastatin has been demonstrated to promote bone formation and reduce bone adsorption."	( Multiple drilling combined with simvastatin versus multiple drilling alone for the treatment of avascular osteonecrosis of the femoral head: 3-year follow-up study. Wang, D; Yin, H; Yuan, Z, 2016)	1.44
"Simvastatin has been reported to exhibit antitumor activities in several cancers; however, its roles and molecular mechanismsin the regulation of colorectal angiogenesis remain to be clarified."	( Simvastatin inhibits tumor angiogenesis in HER2-overexpressing human colorectal cancer. Li, G; Ling, J; Qiu, W; Wang, Y; Xu, B; Zheng, J, 2017)	2.62
"Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, anti-angiogenesis, and apoptosis. "	( Simvastatin plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line chemotherapy in metastatic colorectal patients: a multicenter phase II study. Ahn, JB; Byun, JH; Hong, YS; Im, SA; Jung, KH; Kang, WK; Kim, TW; Lee, J; Lee, N; Lim, HY; Oh, DY; Park, JO; Park, SH; Park, YS; Shin, DB; Shin, SJ, 2009)	3.24
"Simvastatin has the capacity to prevent endotoxemic liver injury by inhibiting leukocyte infiltration and hepatocellular apoptosis. "	( Inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase reduces leukocyte recruitment and hepatocyte apoptosis in endotoxin-induced liver injury. Laschke, MW; Menger, MD; Schilling, MK; Slotta, JE; Thorlacius, H; Wang, Y, 2009)	1.8
"Simvastatin has antiinflammatory effects in the pulmonary and systemic compartment in humans exposed to inhaled LPS."	( Simvastatin decreases lipopolysaccharide-induced pulmonary inflammation in healthy volunteers. Backman, JT; Brown, V; Craig, TR; Elborn, JS; Matthay, MA; McAuley, DF; McKeown, ST; O'Kane, CM; Shyamsundar, M; Taggart, CC; Thickett, DR, 2009)	3.24
"Simvastatin (SIM) has been found to have other clinical benefits besides those resulted from its actions of reducing plasma level of low density lipoprotein (LDL) cholesterol."	( Effect of simvastatin on culturing of kidney cells from pigs in vitro. Fu, J; Lin, H; Liu, G; Wang, A, 2010)	1.48
"Simvastatin has been shown to ameliorate pulmonary hypertension by several mechanisms in experimental animal models. "	( Simvastatin ameliorates established pulmonary hypertension through a heme oxygenase-1 dependent pathway in rats. Chen, CF; Chen, JS; Hsu, HH; Hsu, JY; Ko, WJ; Lai, IR; Lee, YC, 2009)	3.24
"Simvastatin has been reported to promote osteoblastic activity and inhibit osteoclastic activity."	( The use of simvastatin in bone regeneration. Park, JB, 2009)	1.46
"Simvastatin may has a potential therapeutic target in diabetic nephropathy, which may be partly attributed to down-regulating over-expression of MMP-9 in renal tissue."	( Simvastatin protects diabetic rats against kidney injury through the suppression of renal matrix metalloproteinase-9 expression. Chen, K; Chen, Y; Li, XC; Wang, YX; Yang, GW; Yao, XM; Ye, SD; Zai, Z, 2010)	3.25
"Simvastatin has an inhibitory effect on the differentiation and maturation of DC, and selectively reduce the T-cell proliferation induced by DC from patients with ON."	( Increased immunopotency of monocyte derived dendritic cells from patients with optic neuritis is inhibited in vitro by simvastatin. Frederiksen, J; Svane, IM; Tsakiri, A; Tsiantoulas, D, 2010)	1.29
"Simvastatin has a dual effect on tumorigenesis. "	( HMG-CoA reductase inhibition causes increased necrosis and apoptosis in an in vivo mouse glioblastoma multiforme model. Bababeygy, SR; Hou, LC; Polevaya, NV; Prugpichailers, T; Steinman, L; Sun, A; Tse, V; Veeravagu, A; Xiong, A; Youssef, S, 2009)	1.8
"Simvastatin has been reported to be effective on stimulation of bone formation. "	( [Effects of simvastatin on bone formation relative factors of trabecular bone and osteogenic differentiation of bone marrow mesenchymal stem cells in young rats]. Han, D; Liu, X; Tian, F; Zhang, H; Zhang, L, 2011)	2.19
"Simvastatin has been shown to enhance the survival of retinal ganglion cells (RGCs) following ischemia-reperfusion (IR) injury by mediating the expression of stress proteins. "	( Simvastatin upregulates Bcl-2 expression and protects retinal neurons from early ischemia/reperfusion injury in the rat retina. Chen, CF; Ko, ML; Peng, PH; Peng, YH, 2011)	3.25
"Simvastatin has been shown to enhance osseointegration of pure titanium implants in osteoporotic rats. "	( Serum bone formation marker correlation with improved osseointegration in osteoporotic rats treated with simvastatin. Chen, J; Doan, N; Du, Z; Ivanovski, S; Xiao, Y; Yan, F, 2013)	2.05
"Simvastatin has been shown to play an important role in reducing the risk of cardiovascular events caused by atherosclerosis. "	( Simvastatin-induced myopathy with concomitant use of cyclosporine: case report. Feng, GW; Li, YP; Ren, XW; Shang, WJ; Yang, WH; Zeng, ZS; Zhang, LR, 2011)	3.25
"Simvastatin has been shown to stimulate new bone growth on rat mandibles, but much of the bone is lost over time. "	( Impact of local and systemic alendronate on simvastatin-induced new bone around periodontal defects. Killeen, AC; Marx, DB; Narayana, N; Payne, JB; Rakes, PA; Reinhardt, RA; Schmid, MJ; Wang, D; Zhang, Y, 2012)	2.08
"Simvastatin has been clearly shown to decrease LDL-cholesterol, which is associated with the slowing of atherosclerosis and a reduction in cardiovascular morbidity and mortality. "	( The ezetimibe controversy - can this be resolved by comparing the clinical trials with simvastatin and ezetimibe alone and together? Doggrell, SA, 2012)	2.04
"Simvastatin has no clinically important effect on sitagliptin pharmacokinetics. "	( The effects of simvastatin on the pharmacokinectics of sitagliptin. Anderson, MS; Cerra, M; Li, SX; Luo, WL; Matthews, C; O'Neill, EA; Stoch, SA; Wagner, JA, 2012)	2.17
"Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. "	( Controlled release of simvastatin from biomimetic β-TCP drug delivery system. Ben-Nissan, B; Bishop, D; Chou, J; Ito, T; Milthorpe, B; Otsuka, M, 2013)	2.15
"Simvastatin has also been shown to abolish the progression, and even facilitate the regression, of existing human atherosclerotic lesions."	( Benefits and risks of simvastatin in patients with familial hypercholesterolaemia. Alonso, R; Badimón, J; Mata, P, 2003)	1.35
"Simvastatin has reported putative antifibrotic actions in renal fibroblasts; this study explores such actions on human IPF-derived and normal lung fibroblasts and examines associated driving mechanisms."	( Connective tissue growth factor expression and induction by transforming growth factor-beta is abrogated by simvastatin via a Rho signaling mechanism. Spiteri, MA; Watts, KL, 2004)	1.26
"Simvastatin has been shown to inhibit endothelin-1."	( Effect of simvastatin on left ventricular mass in hypercholesterolemic rabbits. Chang, NC; Chou, TF; Lee, TM; Lin, MS, 2005)	1.45
"Simvastatin has been studied in two large outcome trials, the Scandinavian Simvastatin Survival Study (4S), and the Heart Protection Study (HPS), both of which demonstrated strikingly beneficial effects on a variety of cardiovascular outcomes, with minimal adverse effects."	( Simvastatin: a review. Pedersen, TR; Tobert, JA, 2004)	2.49
"Simvastatin has been shown to increase bone growth when applied topically to murine bone; however, it causes considerable soft tissue inflammation at high doses (2.2 mg), making future clinical use problematic. "	( Local simvastatin effects on mandibular bone growth and inflammation. Cullen, DM; Genrich, MA; Killpack, B; Lee, Y; Marx, DB; Narayana, N; Reinhardt, RA; Schmid, MJ; Stein, D, 2005)	2.25
"Simvastatin has statistically significant effects on affect and affective processes in elderly volunteers. "	( Simvastatin causes changes in affective processes in elderly volunteers. Cary, M; Datto, C; DiFilippo, S; Katz, IR; Morales, K; TenHave, T; Wittink, M, 2006)	3.22
"Simvastatin therapy has been proposed as a means to treat the CNS."	( Development and characterization of a hypomorphic Smith-Lemli-Opitz syndrome mouse model and efficacy of simvastatin therapy. Correa-Cerro, LS; Fliesler, SJ; Grinberg, A; Kratz, L; Miller, GF; Munasinghe, JP; Porter, FD; Wassif, CA, 2006)	1.27
"Simvastatin acid (SVA) has been reported to stimulate bone formation with increased expression of BMP-2. "	( Oxygen plasma surface modification enhances immobilization of simvastatin acid. Hayakawa, T; Ide, T; Inoue, T; Matsuzaka, K; Oda, Y; Shimono, M; Tanaka, T; Yoshinari, M, 2006)	2.02
"Simvastatin has a preventive effect on rat PH, it inhibits mast cell proliferation may be one of mechanism."	( [The change of mast cells and macrophages in the lung of rat with pulmonary hypertension]. Dou, H; Li, P; Su, J; Zhang, T; Zhao, L; Zhao, Y; Zhou, TF, 2006)	1.06
"Simvastatin has been shown in experimental models to stimulate bone acting growth factors and enhance bone formation."	( The use of simvastatin in rabbit posterolateral lumbar intertransverse process spine fusion. Bae, HW; Friess, D; Johnstone, B; Robbin, M; Roth, SM; Whyne, C; Yee, AJ; Yoo, JU, )	1.24
"Simvastatin has been shown to restore endothelial function in children with familial hypercolesterolemia after 28 weeks of treatment. "	( One-month therapy with simvastatin restores endothelial function in hypercholesterolemic children and adolescents. Barros, MR; Bertolami, MC; Carvalho, AC; de Matos Barretto, RB; Ferreira, WP; Fonseca, FH; Pontes, SC; Santos, SN, )	1.88
"Simvastatin acid (SVA) has been reported to stimulate bone formation by increasing expression of BMP-2 in osteoblasts. "	( Controlled release of simvastatin acid using cyclodextrin inclusion system. Hashimoto, S; Ide, T; Inoue, T; Ishihara, K; Matsuzaka, K; Oda, Y; Tanaka, T; Yoshinari, M, 2007)	2.1
"Simvastatin has been shown to reduce the risk of cardiovascular disease by 35% and overall mortality by up to 30% over 5 years."	( Simvastatin: present and future perspectives. Robinson, JG, 2007)	2.5
"Simvastatin has a strong anti-inflammatory effect on HPBM cells including upregulation of the atheroprotective factor KLF-2. "	( Simvastatin has an anti-inflammatory effect on macrophages via upregulation of an atheroprotective transcription factor, Kruppel-like factor 2. Häkkinen, SK; Horrevoets, AJ; Kansanen, E; Levonen, AL; Lumivuori, H; Tuomisto, TT; Turunen, MP; van Thienen, JV; Ylä-Herttuala, S, 2008)	3.23
"Simvastatin therapy has been demonstrated to significantly improve endothelial function in these patients."	( Short-term withdrawal of simvastatin induces endothelial dysfunction in patients with coronary artery disease: a dose-response effect dependent on endothelial nitric oxide synthase. Chen, H; Liu, X; Luo, Y; Ren, JY; Wang, RJ; Wu, P; Xing, Y; Zhang, WL, 2009)	1.38
"Simvastatin also has a preventive effect on the progression of preexisting CAs."	( Simvastatin suppresses the progression of experimentally induced cerebral aneurysms in rats. Aoki, T; Hashimoto, N; Ishibashi, R; Kataoka, H; Nozaki, K, 2008)	2.51
"Simvastatin has potential application in diabetes-related wound healing disorders."	( Simvastatin enhances VEGF production and ameliorates impaired wound healing in experimental diabetes. Altavilla, D; Bitto, A; Bonaiuto, M; Calò, M; Caputi, AP; Fiumara, T; Galeano, M; Lo Cascio, P; Marini, H; Migliorato, A; Minutoli, L; Polito, F; Squadrito, F, 2008)	2.51
"Simvastatin has the effect of anti-inflammation, which may play some protection against the progress of atherosclerosis in diabetic rats."	( The effect of simvastatin on the serum monocyte chemoattractant protein-1 and intracellular adhesion molecule-1 levels in diabetic rats. Chen, Y; Fan, A; Li, X; Lin, Y; Wang, Y; Yang, GW; Ye, S, )	1.93
"Simvastatin has been shown to stimulate osteogenesis both in vitro and in vivo. "	( Simvastatin induces estrogen receptor-alpha (ER-alpha) in murine bone marrow stromal cells. Chen, Z; Dang, G; Jia, H; Li, X; Liu, Z; Ma, Q; Song, C; Song, Q; Wang, J, 2008)	3.23
"Simvastatin treatment has been well tolerated by the patients."	( [Simvastatin in the treatment of familial hypercholesterolemia]. Ceska, R; Kvasilová, M; Procházková, R; Sobra, J, 1995)	1.92
"Simvastatin has also been shown to potentiate the effects of warfarin [corrected].(ABSTRACT TRUNCATED AT 250 WORDS)"	( Clinical pharmacokinetics and practical applications of simvastatin. Mauro, VF, 1993)	1.25
"Simvastatin has a beneficial effect on abnormal lipid levels in SRNS but the effectiveness of long-term therapy needs to be evaluated."	( Hyperlipidaemia, diet and simvastatin therapy in steroid-resistant nephrotic syndrome of childhood. Coleman, JE; Watson, AR, 1996)	1.32
"Simvastatin has this effect at doses of about half those of the other 3 statins."	( Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences. Fager, G; Lennernäs, H, 1997)	1.02
"Simvastatin therapy has been shown to be cost-effective, decreasing per-patient hospitalization costs by 31% or $3,872 in 1995 dollars."	( Coronary artery disease: the Scandinavian Simvastatin Survival Study experience. Pedersen, TR, 1998)	1.29
"Simvastatin (Zocor) has been linked to three cases of drug-induced lupus-like syndrome."	( Simvastatin-induced lupus-like syndrome. Ahmad, A; Fletcher, MT; Roy, TM, 2000)	2.47
"Simvastatin 40 to 80 mg/d has been found to increase high-density lipoprotein cholesterol (HDL-C) levels significantly more than atorvastatin at equipotent doses (ie, 20-80 mg/d). "	( Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia. Berra, C; Branchi, A; Colombo, E; Dalla Valle, E; Fiorenza, AM; Muzio, F; Rovellini, A; Sommariva, D; Torri, A, 2001)	2.06
"2. Simvastatin has been studied for its effects on hepatic microsomal drug metabolism in rat."	( Effects of simvastatin, a lipoprotein-lowering drug, on the hepatic enzymes involved in drug metabolism in the Wistar rat. Escousse, A; Goudonnet, H; Mercenne, F; Mounie, J; Truchot, RC, 1991)	1.19

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Simvastatin could enhance protective autophagy by activating the AMPK-SKP2-CARM1 pathway to improve erectile function in diabetes mellitus-induced erectile dysfunction rats. Simvastin (SMV) could increase tooth anchorage during orthodontic tooth movement (OTM) Simvstatin can enhance theraprutic effect of many kinds of stem cells by increasing numbe.

Excerpt	Reference	Relevance
"Simvastatin plays an important role in reducing inflammation."	( Simvastatin Improves Outcomes of Endotoxin-induced Coagulopathy by Regulating Intestinal Microenvironment. Du, MY; Hu, Y; Luo, LL; Mei, H; Tang, L; Xu, M; Zhou, J, 2022)	2.89
"Simvastatin could inhibit the metabolism of vonoprazan in vitro but multiple doses of simvastatin exhibited the opposite effect In vivo. "	( Effects of Simvastatin on the Metabolism of Vonoprazan in Rats Both in vitro and in vivo. Cai, JP; Dai, DP; Geng, PW; Hong, Y; Luo, QF; Shi, JH; Wang, SH; Wang, YR; Xu, X; Zhao, FL; Zhou, Q; Zhou, S; Zhou, YF, 2022)	2.55
"Simvastatin may inhibit the progression of IL-33-induced inflammation via suppressing JNK to prevent MCP-1 production."	( Inhibitory Effects of Simvastatin on IL-33-Induced MCP-1 via the Suppression of the JNK Pathway in Human Vascular Endothelial Cells. Jougasaki, M; Sudou, K; Takenoshita, Y; Tokito, A; Umebashi, K; Yamamoto, M, 2023)	1.95
"Simvastatin could enhance protective autophagy by activating the AMPK-SKP2-CARM1 pathway to improve erectile function in diabetes mellitus-induced erectile dysfunction rats."	( Simvastatin alleviated diabetes mellitus-induced erectile dysfunction in rats by enhancing AMPK pathway-induced autophagy. Dai, Q; Ding, F; Guo, C; Li, H; Ouyang, Q; Shan, C; Shen, W; Wu, X; Zhang, Y; Zheng, J; Zhou, Z, 2020)	3.44
"Simvastatin can inhibit the HIF-1α/PPAR-γ/PKM2 axis, by suppressing PKM2-mediated glycolysis, resulting in decreased proliferation and increased apoptosis in HCC cells, and re-sensitizing HCC cells to Sora."	( Simvastatin re-sensitizes hepatocellular carcinoma cells to sorafenib by inhibiting HIF-1α/PPAR-γ/PKM2-mediated glycolysis. Chen, K; Dai, W; Feng, J; Guo, C; Ji, J; Kong, R; Li, J; Li, S; Mao, Y; Mo, W; Wu, J; Wu, L; Xu, X; Yu, Q; Zhang, J, 2020)	3.44
"Simvastatin promotes myostatin expression in both skeletal muscle and brown adipose tissue through inhibiting GGPP production; 3."	( Statins induce skeletal muscle atrophy via GGPP depletion-dependent myostatin overexpression in skeletal muscle and brown adipose tissue. Chen, J; Li, P; Meng, L; Wang, L; Yang, H; Zheng, ZG; Zhu, L, 2021)	1.34
"Simvastatin (SMV) could increase tooth anchorage during orthodontic tooth movement (OTM). "	( Local delivery of simvastatin maintains tooth anchorage during mechanical tooth moving via anti-inflammation property and AMPK/MAPK/NF-kB inhibition. Baban, B; Mao, J; Qin, X; Sun, X; Xu, L; Zhu, G, 2021)	2.4
"The simvastatin can enhance the theraprutic effect of many kinds of stem cells by increasing number and function of the stem cell."	( A new in vivo method to retard progression of intervertebral disc degeneration through stimulation of endogenous stem cells with simvastatin. Bi, S; Chen, T; Feng, X; Huang, Z; Zhang, L, 2017)	1.14
"Simvastatin tended to increase ceramide abundance, an effect, however, escaping statistical significance."	( Simvastatin, a Novel Stimulator of Eryptosis, the Suicidal Erythrocyte Death. Al Mamun Bhuyan, A; Cao, H; Lang, F; Nüßle, S; Zhang, S, 2017)	2.62
"Simvastatin appeared to increase hepatic sinusoidal function and reduce portal hypertension and markers of inflammation and oxidation."	( Simvastatin Prevents Progression of Acute on Chronic Liver Failure in Rats With Cirrhosis and Portal Hypertension. Bosch, J; Fernández-Iglesias, A; Garcia-Calderó, H; García-Pagán, JC; Gracia-Sancho, J; Lafoz, E; Rodrigues de Oliveira, J; Tripathi, DM; Viegas Haute, G; Vilaseca, M, 2018)	2.64
"Simvastatin (SVS) promotes the osteogenic differentiation of mesenchymal stem cells (MSCs) and has been studied for MSC-based bone regeneration. "	( Alpha-5 Integrin Mediates Simvastatin-Induced Osteogenesis of Bone Marrow Mesenchymal Stem Cells. Chen, CH; Ho, ML; Lin, ZY; Shao, PL; Wang, CZ; Wu, SC, 2019)	2.26
"Simvastatin caused an increase in p53 phosphorylation and acetylation."	( Simvastatin induced HCT116 colorectal cancer cell apoptosis through p38MAPK-p53-survivin signaling cascade. Chang, HL; Chen, CY; Chiu, PT; Hsu, MJ; Hsu, YF; Huang, YH; Kuo, WS; Ou, G, 2013)	2.55
"Simvastatin can delay and inhibit prostatic hyperplasia and progression in SHR. "	( Influence and pathophysiological mechanisms of simvastatin on prostatic hyperplasia in spontaneously hypertensive rats. Dong, L; Qu, X; Shen, F; Zhang, X; Zhao, X, 2013)	2.09
"Simvastatin can cause a marked decrease in plasma Hcy levels. "	( Effect of simvastatin on plasma homocysteine levels and its modification by MTHFR C677T polymorphism in Chinese patients with primary hyperlipidemia. Chen, Q; Hsu, YH; Jiang, S; Venners, SA; Wang, X; Xing, H; Xu, X; Zhong, G, 2013)	2.23
"Simvastatin may inhibit VSMC phenotype modulation and proliferation by downregulating the expression of PCNA and upregulating that of p27kip1."	( Simvastatin decreases stent-induced in-stent restenosis rate via downregulating the expression of PCNA and upregulating that of p27kip1. Gao, C; Li, M; Xiao, W; Xu, W; Yu, J, 2013)	3.28
"Simvastatin may inhibit inflammation by enhancing the switching of M1 macrophage to M2 macrophage phenotype."	( [Anti-inflammation of simvastatin by polarization of murine macrophages from M1 phenotype to M2 phenotype]. Han, JJ; Li, QZ; Qian, ZJ; Sun, J, 2013)	2.15
"Simvastatin could also inhibit the expression of NMDAR1 and cytokines to a degree similar to silencing of NMDAR1 with siRNA."	( Simvastatin prevents neuroinflammation by inhibiting N-methyl-D-aspartic acid receptor 1 in 6-hydroxydopamine-treated PC12 cells. Du, G; Fu, Q; Huang, L; Sun, J; Yan, J, 2014)	2.57
"The simvastatin group had lower DLQI scores (P < 0·001) post-treatment."	( Simvastatin as a novel therapeutic agent for venous ulcers: a randomized, double-blind, placebo-controlled trial. Casintahan, MF; Evangelista, MT; Villafuerte, LL, 2014)	2.33
"Simvastatin (SIM) can increase osteoblast activity and enhance osteogenesis. "	( Synthesis and characterization of cationic polymeric nanoparticles as simvastatin carriers for enhancing the osteogenesis of bone marrow mesenchymal stem cells. Fu, YC; Ho, ML; Jian, SC; Liu, PL; Wang, CK; Wang, CZ; Wang, YH, 2014)	2.08
"Simvastatin was shown to activate a stress cascade, leading to the synthesis of 15-deoxy-12,14-PGJ2 (15d-PGJ2 ), in a p38- and COX-2-dependent manner. "	( Autocrine secretion of 15d-PGJ2 mediates simvastatin-induced apoptotic burst in human metastatic melanoma cells. Hohenegger, M; Höller, C; Künzl, M; Minichsdorfer, C; Wasinger, C; Zellner, M, 2014)	2.11
"Simvastatin could increase expression of exon-IIC transcripts in stressed mice."	( Alteration in the expression of exon IIC transcripts of brain-derived neurotrophic factor gene by simvastatin [correction of simvastain] in chronic mild stress in mice: a possible link with dopaminergic pathway. Goyal, RK; Jhala, MK; Joshi, CG; Patel, AK; Rana, DG, 2014)	1.34
"Simvastatin can inhibit proliferation of PASMC and cell cycle process. "	( [Effect of NF-κB on proliferation of rat pulmonary artery smooth muscle cells inhibited by simvastatin]. Liu, HM; Liu, ZQ; Wang, XQ, 2015)	2.08
"Simvastatin did not inhibit the relapse of tooth movement in rats, and there was no correlation between bone density and orthodontic relapse."	( The effect of simvastatin on relapse of tooth movement and bone mineral density in rats measured by a new method using microtomography. Amorim, RF; Chaves, SB; Ferreira, VM; Freitas, KM; Vieira, GM, 2015)	2.22
"Simvastatin did, however, increase neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and AMPK α-subunit protein expression, and tended to increase total NOS activity, in FT but not ST muscles."	( Statin-Induced Increases in Atrophy Gene Expression Occur Independently of Changes in PGC1α Protein and Mitochondrial Content. Goodman, CA; Lee-Young, RS; McConell, GK; Pol, D; Russell, AP; Snow, RJ; Zacharewicz, E, 2015)	1.14
"Simvastatin treatment promotes EAE clinical amelioration by inhibiting T cell proliferation and CNS infiltration by pathogenic Th1 and Th17 cells."	( Simvastatin ameliorates experimental autoimmune encephalomyelitis by inhibiting Th1/Th17 response and cellular infiltration. Câmara, NO; Cenedeze, MA; de Oliveira, DM; de Oliveira, EM; Ferrari, Mde F; Hiyane, MI; Pacheco-Silva, A; Peron, JP; Semedo, P, 2015)	3.3
"Simvastatin did not increase survival of patients with Child-Pugh class C cirrhosis."	( Addition of Simvastatin to Standard Therapy for the Prevention of Variceal Rebleeding Does Not Reduce Rebleeding but Increases Survival in Patients With Cirrhosis. Abraldes, JG; Albillos, A; Aracil, C; Bosch, J; Calleja, JL; Castellote, J; García-Pagán, JC; Genesca, J; Hernandez-Guerra, M; Rodriguez, M; Torres, F; Turnes, J; Villanueva, C, 2016)	1.53
"Simvastatin can also inhibit the formation of other products, such as isoprenoids, conferring additional benefits to this drug, which include antiproliferative, anti-invasive and pro-apoptotic effects."	( Modulating effect of simvastatin on the DNA damage induced by doxorubicin in somatic cells of Drosophila melanogaster. Nepomuceno, JC; Orsolin, PC; Silva-Oliveira, RG, 2016)	1.47
"Simvastatin reported to cause muscle cramps while fluticasone is well documented to cause oral candidiasis."	( Exploring New Zealand prescription data using sequence symmetry analyses for predicting adverse drug reactions. Chyou, TY; Nishtala, PS, 2017)	1.18
"Simvastatin tends to cause deterioration in exercise-associated cardiorespiratory fitness and skeletal muscle mitochondrial content in adults with T2DM, which is blunted by vitamin D supplementation."	( Vitamin D supplementation improves simvastatin-mediated decline in exercise performance: A randomized double-blind placebo-controlled study. Aggarwal, AN; Badal, D; Bhansali, A; Bhat, OM; Rastogi, A; Singla, M, 2017)	2.17
"Simvastatin induced the increase of [Ca2+]i in K562 cells, fluorescent intensities were 43, 54, and 64, respectively."	( [Simvastatin-induced apoptosis of K562 cells is mediated by endoplasmic reticulum stress]. Huang, WF; Liu, H; Liu, W; Xu, GQ; Yang, YC, 2008)	1.98
"Simvastatin promotes detachment and EMP release by inhibiting prenylation, presumably via a caspase 8-dependent mechanism."	( Simvastatin-induced endothelial cell detachment and microparticle release are prenylation dependent. Abid-Hussein, MN; Böing, AN; Diamant, M; Hau, CM; Nieuwland, R; Sturk, A; Tushuizen, ME, 2008)	2.51
"Simvastatin could inhibit K562 cell proliferation, and the inhibition rate was approximately 30% after treatment with 20 mumol/l simvastatin for 48 h. "	( In vitro and in vivo study of cell growth inhibition of simvastatin on chronic myelogenous leukemia cells. Chuan, LM; Hu, Q; Huang, B; Huang, WF; Liu, W; Xiao, DW; Xu, GQ; Yang, YC; Zeng, YL; Zhou, DA, 2008)	2.03
"Simvastatin can inhibit CML cell proliferation in vitro and in vivo, and its mechanisms might be involved in cell cycle regulation."	( In vitro and in vivo study of cell growth inhibition of simvastatin on chronic myelogenous leukemia cells. Chuan, LM; Hu, Q; Huang, B; Huang, WF; Liu, W; Xiao, DW; Xu, GQ; Yang, YC; Zeng, YL; Zhou, DA, 2008)	2.03
"Simvastatin is shown to increase cancellous bone volume, bone formation rate, and cancellous bone compressive strength."	( The use of simvastatin in bone regeneration. Park, JB, 2009)	1.46
"Simvastatin was shown to increase the expression of Bone morphogenetic protein (BMP-2), which is one of the most potent growth factors targeting bone formation."	( Simvastatin locally applied from a biodegradable coating of osteosynthetic implants improves fracture healing comparable to BMP-2 application. Haas, NP; Luttosch, F; Morawski, M; Pauly, S; Schmidmaier, G; Wildemann, B, 2009)	2.52
"Simvastatin may inhibit cigarette smoke-induced small airway remodelling by reducing growth factor expression and inflammation."	( Simvastatin attenuates experimental small airway remodelling in rats. Chen, L; Feng, YL; Huang, XY; Liu, DS; Ou, XM; Uhal, BD; Wang, K; Wang, T; Wang, X; Wen, FQ, 2009)	2.52
"Simvastatin-induced increase in clot permeability was associated only with age and decrease in CRP levels (R2 for the model = 0.61), while shortening of clot lysis time observed following simvastatin use was predicted only by reduction of triglycerides and CRP (R2 for the model = 0.62)."	( Simvastatin increases clot permeability and susceptibility to lysis in patients with LDL cholesterol below 3.4 mmol/l. Topór-Madry, R; Tracz, W; Undas, A, 2009)	2.52
"Simvastatin induced an increase of caspase-3 activity and annexin V staining, and down-regulated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway."	( Effect of simvastatin on glioma cell proliferation, migration, and apoptosis. Chopp, M; Jiang, H; Lu, D; Mahmood, A; Qu, C; Wu, H; Xiong, Y; Zhou, D, 2009)	1.48
"Simvastatin plays a protective role in CSE-induced fibrinolytic malfunction."	( Effects of simvastatin on cigarette smoke extract induced tissue-type plasminogen activator and plasminogen activator inhibitor-1 expression in human umbilical vein endothelial cells. Hu, XY; Ma, YH; Wang, C; Yang, YH, 2009)	1.46
"Simvastatin can inhibit the expression of bone absorptive factors induced by wear particles and may be used in the prevention and treatment of aseptic loosening of prosthesis."	( [Experimental study on simvastatin in prevention and treatment of aseptic loosening of prosthesis]. Gao, X; Jin, Q; Sun, K; Wang, Z, 2010)	1.39
"Simvastatin could also increase cyclin-dependent kinase inhibitor p21 protein expression (F = 512.133, P value less than 0.001)."	( [Effects of simvastatin on the proliferation of HepG2 cells]. Liu, W; Zhang, LF; Zhang, YH, 2010)	1.46
"Simvastatin can inhibit the growth of HepG2 cells in vitro, which may be explained by its effects of enhancing cyclin-dependent kinase inhibitor p21 protein expression and arresting HepG2 cells at G0/G1 phase of cell cycle."	( [Effects of simvastatin on the proliferation of HepG2 cells]. Liu, W; Zhang, LF; Zhang, YH, 2010)	2.18
"Simvastatin also promotes angiogenesis in vitro."	( Induction of angiogenesis and modulation of vascular endothelial growth factor receptor-2 by simvastatin after traumatic brain injury. Chopp, M; Jiang, H; Lu, D; Mahmood, A; Qu, C; Wu, H; Xiong, Y; Zhou, D, 2011)	1.31
"Simvastatin was found to suppress these H2O2-induced signaling pathways in osteoclastogenesis."	( Simvastatin inhibits osteoclast differentiation by scavenging reactive oxygen species. Bang, JB; Hwang, YS; Kim, SE; Kwon, IK; Moon, HJ; Park, JH; Yun, YP, 2011)	2.53
"Simvastatin induced an increase in eNOS mRNA expression and protein levels in the presence of arginine or citrulline."	( Arginine or citrulline associated with a statin stimulates nitric oxide production in bovine aortic endothelial cells. Bernard, M; Berthe, MC; Couderc, R; Cynober, L; Darquy, S; Rasmusen, C, 2011)	1.09
"Simvastatin is used to lower cholesterol and also exhibits antifungal action."	( In vitro synergism of simvastatin and fluconazole against Candida species. Cunha, FA; Cunha, Mda C; Menezes, EA; Plutarco, FX; Silva, CL; Vasconcelos Júnior, AA, 2012)	1.41
"Simvastatin could inhibit the expression of CTGF in the vitreous body and retina in diabetic rats. "	( [Effects of simvastatin on expression of connective tissue growth factor in vitreous and retina of diabetic rats]. Hu, YB; Liu, YM; Sun, ZY; Yan, H; Zhang, JK, 2012)	2.2
"Simvastatin was found to inhibit increased ERK activation and Ki-67 expression in VSMCs subjected to stretch stress with or without oxLDL."	( Simvastatin inhibits the additive activation of ERK1/2 and proliferation of rat vascular smooth muscle cells induced by combined mechanical stress and oxLDL through LOX-1 pathway. Li, C; Li, Y; Liu, S; Ning, F; Ping, S; Wang, J; Xie, F; Zhang, M; Zhang, Z, 2013)	2.55
"Simvastatin and tBHQ suppress KLF1 and BCL11 gene expression and additively increase fetal hemoglobin in primary human erythroid cells. "	( Simvastatin and t-butylhydroquinone suppress KLF1 and BCL11A gene expression and additively increase fetal hemoglobin in primary human erythroid cells. Lowrey, CH; Macari, ER; Schaeffer, EK; West, RJ, 2013)	3.28
"Simvastatin promotes odontoblastic differentiation of hDPCs via the ERK signaling pathway. "	( Combined effects of simvastatin and enamel matrix derivative on odontoblastic differentiation of human dental pulp cells. Karanxha, L; Min, KS; Nör, JE; Park, SJ; Son, WJ, 2013)	2.16
"Simvastatin plays a beneficial role in inflammatory arthritis through its up-regulation of SIRT-1/FoxO3a signaling in synovial fibroblasts."	( Simvastatin inhibits cysteine-rich protein 61 expression in rheumatoid arthritis synovial fibroblasts through the regulation of sirtuin-1/FoxO3a signaling. Chang, CC; Hong, CY; Hou, KL; Hsiao, M; Kok, SH; Lai, EH; Lin, LD; Lin, SK; Wang, JH, 2013)	2.55
"Simvastatin can enhance the amount and function of EPC from bone marrow in diabetic rats in a dose-dependent manner."	( [Effect of simvastatin on the amount and function of endothelial progenitor cells from bone marrow in diabetic rats]. Chen, S; Han, Q; Yan, H; Zhang, W, 2012)	2.21
"Simvastatin could inhibit ox-LDL-induced ER stress and reduce the expression of TNF-α and MCP-1 at mRNA and protien level in dose dependent manner."	( Simvastatin inhibits ox-LDL-induced inflammatory adipokines secretion via amelioration of ER stress in 3T3-L1 adipocyte. Chen, YQ; Wu, ZH; Zhao, SP, 2013)	2.55
"Simvastatin induced an increase in the levels of mRNA for HSP27."	( Mechanism of simvastatin on induction of heat shock protein in osteoblasts. Hatakeyama, D; Hirade, K; Ito, H; Kato, K; Kozawa, O; Niwa, M; Tokuda, H; Wang, X, 2003)	1.41
"Oral simvastatin might inhibit inflammatory components of multiple sclerosis that lead to neurological disability."	( Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Corboy, J; Durkalski, V; Key, L; Markovic-Plese, S; Preiningerova, J; Rizzo, M; Singh, I; Tyor, W; Vollmer, T, 2004)	1.29
"Simvastatin does not lower the triglycerides level through depression of liver protein syntesis, other mechanisms being probably involved."	( The effect of Simvastatin upon serum pseudocholinesterase and plasmatic factor VII. Bodizs, G; Oprea, M; Predescu, D; Zdrenghea, D; Zdrenghea, M, 2002)	2.12
"Simvastatin displays significant antimyeloma activity in vitro. "	( Simvastatin induces death of multiple myeloma cell lines. Drucker, L; Gronich, N; Lishner, M; Radnay, J; Shapiro, H; Yarkoni, S, 2004)	3.21
"Simvastatin failed to inhibit activation of these signaling pathways."	( Simvastatin inhibits MMP-9 secretion from human saphenous vein smooth muscle cells by inhibiting the RhoA/ROCK pathway and reducing MMP-9 mRNA levels. Ball, SG; O'Regan, DJ; Porter, KE; Turner, NA, 2005)	2.49
"Simvastatin did not cause morphologic changes or cytotoxicity in the fibroblasts, even after 4 days of treatment. "	( Inhibition of systemic sclerosis dermal fibroblast type I collagen production and gene expression by simvastatin. Fertala, J; Huaman, G; Jiménez, SA; Louneva, N, 2006)	1.99
"Simvastatin induced an increase in blood velocity and blood flow in retinal arteries and veins, increased the plasma nitrite/nitrate levels, and decreased the intraocular pressure, probably through the increase in nitric oxide."	( Effect of systemic administration of simvastatin on retinal circulation. Hein, TW; Izumi, N; Kuo, L; Nagaoka, T; Sato, E; Takahashi, A; Yoshida, A, 2006)	2.05
"Simvastatin induced an increase in blood velocity and blood flow in retinal arteries and veins, increased the plasma nitrite/nitrate levels, and decreased the intraocular pressure, probably through the increase in nitric oxide."	( The manifold actions of statins. Comment on "Effects of systemic administration of simvastatin on retinal circulation, by T. Nagaoka, A. Takahashi, E. Sato, et al. Arch Ophthalmol 124:665-70, 2006. Arroyo, JG, )	1.8
"Simvastatin was found to inhibit growth, and this was associated with lower ergosterol levels."	( Simvastatin reduces ergosterol levels, inhibits growth and causes loss of mtDNA in Candida glabrata. Macreadie, IG; Westermeyer, C, 2007)	2.5
"Simvastatin does not enhance endothelial function in subjects with elevated ADMA, whereas it does so in patients with low ADMA. "	( Asymmetric dimethylarginine determines the improvement of endothelium-dependent vasodilation by simvastatin: Effect of combination with oral L-arginine. Benndorf, RA; Bierend, A; Böger, GI; Böger, RH; Dumbadze, E; Maas, R; Rudolph, TK; Schwedhelm, E, 2007)	2
"Simvastatin can inhibit ET-1 expression in endothelial cell cultured hypoxically."	( [Effect of simvastatin on endothelin-1 expression in endothelial cell cultured hypoxically]. Chen, XJ; Cheng, DY; Su, QL; Xia, XQ; Yang, L, 2008)	2.18
"Simvastatin did not inhibit development of atheroma."	( Development and progression of atherosclerosis in aorta from heterozygous and homozygous WHHL rabbits. Effects of simvastatin treatment. Dowell, FJ; Hamilton, CA; Lindop, GB; Reid, JL, 1995)	1.22
"Simvastatin was found to produce significantly greater mean percent reductions from baseline in total cholesterol (28% versus 21%), LDL cholesterol (38% versus 29%), and apolipoprotein B concentrations (25% versus 17%) than did pravastatin, and a greater percentage of patients receiving simvastatin (94% versus 80%) had at least a 20% reduction in LDL cholesterol."	( Efficacy and tolerability of simvastatin 20 mg vs pravastatin 20 mg in patients with primary hypercholesterolemia. European Study Group. Lambrecht, LJ; Malini, PL, 1993)	1.3
"Simvastatin promotes more effective reduction in cholesterol and apoB in LDL than in VLDL, probably by increasing the hepatic LDL receptor which preferentially binds LDL."	( Effects of simvastatin on the number and composition of apoproteinB-containing lipoproteins in hypercholesterolemia: analysis of apoproteinB in each lipoprotein fraction by highly sensitive latex method. Harano, Y; Ikeda Ryomoto, K; Suzuki, M; Tsushima, M; Yamamoto, A, 1996)	1.41
"Simvastatin inhibited the increase of NA-induced increase of RNA content and [(3)H]-leucine incorporation in a concentration-dependent manner."	( Simvastatin inhibits noradrenaline-induced hypertrophy of cultured neonatal rat cardiomyocytes. Chen, X; Guan, JX; Luo, JD; Ma, XD; Xie, F; Zhang, WW, 2001)	2.47
"Simvastatin induced an increase in cytosolic calcium ([Ca(2+)](i)) in BAEC, by releasing Ca(2+) from intracellular stores sensitive to thapsigargin and ryanodine, and increasing Ca(2+) entry."	( Simvastatin and Ca(2+) signaling in endothelial cells: involvement of rho protein. Alvarez de Sotomayor, M; Andriantsitohaina, R, 2001)	2.47
"Simvastatin promotes intracellular antioxidant systems, fundamentally SOD, restoring endothelial function but not having any effect on blood pressure."	( Simvastatin improves endothelial function in spontaneously hypertensive rats through a superoxide dismutase mediated antioxidant effect. Alvarez de Sotomayor, M; Bravo, L; Carneado, J; Herrera, MD; Jimenez, L; Marhuenda, E; Martin-Sanz, MD; Miranda, M; Pamies, E; Perez-Guerrero, C; Stiefel, P, 2002)	3.2
"Simvastatin can also inhibit in vitro the rate of human glioma cell growth, since it shows a strong synergistic inhibitory effect on cell proliferation whe"	( Cholesterol and mevalonic acid modulation in cell metabolism and multiplication. Corsini, A; Paoletti, R; Soma, MR, 1992)	1
"Simvastatin did not cause any subjective or objective side effects, while cholestyramine caused gastrointestinal problems in 31% of patients."	( Comparative effects of simvastatin and cholestyramine in treatment of patients with hypercholesterolaemia. Mölgaard, J; Olsson, AG; von Schenck, H, 1989)	1.31

Treatment

Simvastatin treatment increased plasma NO(2+NO(3) without affecting endothelial function, heart weight index, and blood pressure of control rats. Treatment reduced right ventricular hypertrophy and reduced proliferation and increased apoptosis of pathological smooth muscle cells in the neointima and medial walls of pulmonary arteries.

Excerpt	Reference	Relevance
"Simvastatin treatment markedly enhanced SOD activity and reduced contents of MDA, LDH, and creatine kinase (CK) in MIRI rats. "	( Simvastatin Improves Myocardial Ischemia Reperfusion Injury through KLF-Regulated Alleviation of Inflammation. Fu, G; Huang, C; Huang, G; Li, J; Wei, T; Xu, J; Zhao, H; Zhu, X, 2022)	3.61
"Simvastatin treatment reduced the inflammation score, cytokine levels, total cells, and neutrophil counts in the BALF and reduced proportions of Th2 and Th17 but increased Treg cells in lungs of OVA+LPS mice."	( Simvastatin Reduces NETosis to Attenuate Severe Asthma by Inhibiting PAD4 Expression. Chen, YR; Liu, D; Peng, B; Sun, F; Xiang, XD; Xiao, BW; Yan, MY, 2023)	3.07
"Simvastatin-treated patients showed lower plasma cholesterol (P < .0001), low-density lipoprotein (P < .0001), and triglyceride levels (P = .0116) than controls. "	( Effect of Simvastatin Treatment on Mitochondrial Function and Inflammatory Status of Human White Adipose Tissue. Blom, I; Christensen, IB; Dela, F; Dohlmann, TL; Finger, F; Gerhart-Hines, Z; Helge, JW; Larsen, S, 2023)	2.76
"Simvastatin treatment was linked to mitochondrial respiratory capacity in human subcutaneous white adipose tissue, but no clear link was found between statin exposure, respiratory changes, and inflammatory status of adipose tissue."	( Effect of Simvastatin Treatment on Mitochondrial Function and Inflammatory Status of Human White Adipose Tissue. Blom, I; Christensen, IB; Dela, F; Dohlmann, TL; Finger, F; Gerhart-Hines, Z; Helge, JW; Larsen, S, 2023)	2.76
"Simvastatin treatment significantly opposed testosterone's effect on all aforementioned parameters."	( Simvastatin ameliorates testosterone-induced prostatic hyperplasia in rats via modulating IGF-1/PI3K/AKT/FOXO signaling. El-Shafei, NH; Kandil, EA; Sayed, RH; Zaafan, MA, 2023)	3.07
"In simvastatin-treated ccRCC cells, although RhoA was upregulated, it was mainly restrained in the cytosolic fraction and concomitantly reduced Rho-associated protein kinase activity."	( Tumoricidal Activity of Simvastatin in Synergy with RhoA Inactivation in Antimigration of Clear Cell Renal Cell Carcinoma Cells. Chou, FN; Chou, HC; Fann, YC; Juan, SH; Ko, TL; Lee, YG; Tung, SY, 2023)	1.73
"Simvastatin treatment in HCT116 and SW620 induced pyroptosis and suppressed cell proliferation, with changes in the expression level of NLPR3, ASC, cleaved-caspase-1, mature IL-1β, IL-18 and GSDMD-N. "	( Simvastatin induces pyroptosis via ROS/caspase-1/GSDMD pathway in colon cancer. Liu, Y; Long, Y; Peng, M; Xie, W; Yi, L; Zhang, B, 2023)	3.8
"Simvastatin treatment reduced chondrocyte dedifferentiation induced by retinoic acid or serial monolayer culturing by 50% compared to that in the non-treated cells."	( Simvastatin induces differentiation in rabbit articular chondrocytes via Wnt/β-catenin pathway. Han, Y; Kim, SJ; Yu, SM, 2019)	2.68
"Simvastatin-treated cells reduced phosphorylation of focal adhesion kinase down to 26%-60% of control, whereas it increased total focal adhesion kinase protein expression."	( Simvastatin ameliorates altered mechanotransduction in uterine leiomyoma cells. Afrin, S; Borahay, MA; Catherino, WH; Islam, MS; Malik, M; Patzkowsky, K; Segars, JH, 2020)	2.72
"Simvastatin-treated rats that survived to sepsis showed a reduction in the levels of nitrate, IL1-β, and IL-6 and an increase in Bcl-2 protein expression in the prefrontal cortex and hippocampus, and synaptophysin only in the hippocampus."	( Simvastatin Prevents Long-Term Cognitive Deficits in Sepsis Survivor Rats by Reducing Neuroinflammation and Neurodegeneration. Alberici, LC; Cárnio, EC; Catalão, CHR; da Costa, LHA; Rocha, MJA; Santos-Junior, NN; Sebollela, A; Souza, AO, 2020)	2.72
"Simvastatin treatment lead to significantly reduced viability of NPC cells and the number of cell colonies dose-dependently and time-dependently. "	( Simvastatin induces apoptosis of nasopharyngeal carcinoma cells through NF-κB signaling pathway. Sun, FR; Sun, LM; Wang, M; Wang, SL, 2020)	3.44
"Simvastatin (SV) treatment also alleviated LDL-induced cell viability and migration ability in both the prostate and pancreatic tumor cells."	( LDL cholesterol promotes the proliferation of prostate and pancreatic cancer cells by activating the STAT3 pathway. Ahn, KS; Alharbi, SA; Chinnathambi, A; Jung, YY; Ko, JH; Sethi, G; Um, JY, 2021)	1.34
"Simvastatin treatment improved hemodynamic condition, myocardial tissue remodeling, and myocardial energy metabolism, as well as increasing calmodulin expression in rats with PAH-induced RHF."	( Simvastatin protects heart function and myocardial energy metabolism in pulmonary arterial hypertension induced right heart failure. Kang, P; Tang, B; Wang, H; Wang, X; Xu, J; Xuan, L; Zhang, H; Zhu, L, 2021)	2.79
"Simvastatin treatment, in a dose-related manner, markedly improved the lung histological injury and decreased the levels of TNF-α, IL-1β, and increased IL-10 in LPS induced ALI."	( Simvastatin attenuates acute lung injury by activation of A2B adenosine receptor. Cai, SH; Gao, Y; Li, HX; Liang, XY; Wu, JH; Yuan, YP, 2021)	2.79
"Simvastatin treatment increases circulating EPCs and inhabits the formation of ICA."	( Simvastatin increases circulating endothelial progenitor cells and inhibits the formation of intracranial aneurysms in rats with diet-induced hyperhomocysteinemia. Chen, Y; Dong, H; Li, Y; Wang, S; Wang, X; Wu, J; Xu, Y; Zhang, B, 2021)	2.79
"Simvastatin treatment in animals feed with HFD showed a significant improvement of all tested parameters, but it was associated with hepatotoxicity, myopathy, and histological changes in quadriceps muscles."	( Therapeutic advancement of simvastatin-loaded solid lipid nanoparticles (SV-SLNs) in treatment of hyperlipidemia and attenuating hepatotoxicity, myopathy and apoptosis: Comprehensive study. Abdelsalam, RM; Abo-Zalam, HB; El-Denshary, ES; Hamzawy, MA; Khalil, IA; Khattab, MM, 2021)	1.64
"Simvastatin treatment in healthy, middle-aged adults resulted in preserved WM microstructure and volume at 18 months. "	( Effects of simvastatin on white matter integrity in healthy middle-aged adults. Adluru, N; Asthana, S; Austin, BP; Bendlin, BB; Carlsson, CM; Chappell, RJ; Hunt, JFV; Jacobson, LE; Johnson, SC; Lazar, KK; Ma, Y; Van Hulle, CA; Vogt, NM, 2021)	2.45
"Simvastatin treatment significantly reduced LDL-C, TG and plasma inflammatory mediator levels in CHD patients."	( Impact of matrix metalloproteinase 9 rs3918242 genetic variant on lipid-lowering efficacy of simvastatin therapy in Chinese patients with coronary heart disease. Li, X; Qi, L; Wang, Y; Xu, Y; Zhang, T; Zhi, J, 2017)	1.4
"Simvastatin treatment reduced the mRNA levels of interleukin-6 and interleukin-8 by approximately 50% in TNF-α-stimulated IEC-6 cells."	( Anti-inflammatory effects of simvastatin in nonsteroidal anti-inflammatory drugs-induced small bowel injury. Cho, JH; Chung, JW; Jeong, AR; Kim, EJ; Kim, EK; Kim, JH; Kim, KO; Kim, YJ; Kwon, KA; Park, DK, 2017)	1.47
"Simvastatin treatment could significantly decrease lipid accumulation in murine podocytes and this protective effect was realized through inhibition of the expression of CXCL16 and increase in the expression of nephrin."	( Effect of Simvastatin on Lipid Accumulation and the Expression of CXCL16 and Nephrin in Podocyte Induced by Oxidized LDL. Li, Q; Sun, S; Wang, L; Yao, X, 2018)	2.33
"Simvastatin treatment exerts antiproliferative and differentiating effects on these cells as well as promoting recovery of cellular homeostasis."	( Simvastatin exerts antiproliferative and differentiating effects on MG63 osteoblast-like cells: Morphological and immunocytochemical study. Fernández-Barbero, JE; Galindo-Moreno, P; Magan-Fernandez, A; Mesa, F; O' Valle, F; Ortiz, R, 2018)	2.64
"Simvastatin treatment significantly inhibited cell viability and clonal proliferation in a dose-dependent manner."	( Concurrent treatment with simvastatin and NF-κB inhibitor in human castration-resistant prostate cancer cells exerts synergistic anti-cancer effects via control of the NF-κB/LIN28/let-7 miRNA signaling pathway. Jeong, CW; Kang, M; Kim, HH; Ku, JH; Kwak, C; Lee, HS; Lee, KH, 2017)	1.48
"The simvastatin treated group showed shortening and loss of the tubercles and disappearance of the spines with swelling and twisted shape of the worms."	( Simvastatin exerts antifibrotic effect and potentiates the antischistosomal effects of praziquantel in a murine model: Role of IL10. Aboulfotouh, N; Aladeeb, NM; Elkaref, A; Elmasry, A, 2017)	2.38
"Both simvastatin treatment arms suppressed indices of HDM-induced airway inflammation and goblet cell hyperplasia, but this was significantly greater with prophylactic therapy, in particular, inhibition of neutrophil and eosinophil influx, and cytokine accumulation."	( Prophylactic benefits of systemically delivered simvastatin treatment in a house dust mite challenged murine model of allergic asthma. Basu, S; Bews, HJ; Carlson, JC; Halayko, AJ; Jha, A; Oo, O; Ryu, MH; Schwartz, J; Wong, CS, 2018)	1.19
"The simvastatin-treated groups were treated with different doses of simvastatin i.p."	( Simvastatin protects against acetaminophen-induced liver injury in mice. Cui, R; Feng, Y; Liang, H; Liu, C; Qiu, M; Zhang, J, 2018)	2.4
"Simvastatin treatment was not associated with higher 3-month abstinence or smoking reduction compared to placebo."	( Lack of effects of simvastatin on smoking cessation in humans: A double-blind, randomized, placebo-controlled clinical study. Dugast, E; Ingrand, I; Ingrand, P; Lafay-Chebassier, C; Pérault-Pochat, MC; Saulnier, PJ; Solinas, M, 2018)	1.53
"Simvastatin treatment decreased Cav-1 (p<0.05) and increased eNOS expression (p<0.01) in the AAA wall."	( Lower levels of Caveolin-1 and higher levels of endothelial nitric oxide synthase are observed in abdominal aortic aneurysm patients treated with simvastatin. Bolliger, M; Domenig, C; Habrowska-Górczyńska, DE; Huk, I; Kowalska, K; Neumayer, C; Piastowska-Ciesielska, AW; Piechota-Polanczyk, A, 2018)	1.4
"Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. "	( Effect of simvastatin and ezetimibe on suPAR levels and outcomes. Bang, CN; Boman, K; Eugen-Olsen, J; Forman, JL; Greve, AM; Hodges, GW; Jeppesen, JL; Kesäniemi, YA; Olsen, MH; Ray, S; Wachtell, K, 2018)	2.33
"Simvastatin treatment (0.1, 0.5, and 2.5 μmol/L) blunted ox-LDL-induced expression of PERK (407.8%, 339.1%, and 187.5%, F = 10.121, all P < 0.05, compared with control group) and phosphorylation of eIF2α (407.8%, 339.1%, 187.5%, F = 11.430, all P < 0.05, compared with control group)."	( Inhibitory Effects of Simvastatin on Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Vascular Endothelial Cells. Bai, YP; Tao, YK; Yan, ST; Zhang, GQ; Zhao, SP, 2018)	1.52
"Simvastatin treatment is cardioprotective in patients undergoing noncoronary artery cardiac surgery. "	( Simvastatin Treatment Protects Myocardium in Noncoronary Artery Cardiac Surgery by Inhibiting Apoptosis Through miR-15a-5p Targeting. Cheng, TP; Jian, YP; Li, HM; Li, Y; Liu, C; Liu, X; Ou, JS; Ou, ZJ; Quon, MJ; Shi, MM; Wang, ZP; Wang, ZQ; Xu, YQ; Xu, Z; Zhang, CX; Zhang, W; Zhang, X; Zhou, L, 2018)	3.37
"Simvastatin treatment reduced serum cholesterol levels by 18% and retinal content of cholesterol and lathosterol (but not desmosterol) by 24% and 21%, respectively."	( Retinal Cholesterol Content Is Reduced in Simvastatin-Treated Mice Due to Inhibited Local Biosynthesis Albeit Increased Uptake of Serum Cholesterol. Bederman, IR; Mast, N; Pikuleva, IA, 2018)	1.47
"Simvastatin pretreatment significantly decreased the values of the transaminases alanine aminotransferase and aspartate aminotransferase and improved histological alterations according to improved Suzuki's Score (P < 0.05). "	( Simvastatin ameliorates total liver ischemia/reperfusion injury via KLF2-mediated mechanism in rats. Huang, X; Lai, CH; Li, L; Liu, Z; Luo, J; Qi, X; Senninger, N; Wang, W; Wang, Y; Xiaoli, F; Xiong, Y; Ye, Q; Ye, S; Zhang, X; Zhong, Z, 2019)	3.4
"Simvastatin pretreatment ameliorates total hepatic IRI via a KLF2-mediated protective mechanism. "	( Simvastatin ameliorates total liver ischemia/reperfusion injury via KLF2-mediated mechanism in rats. Huang, X; Lai, CH; Li, L; Liu, Z; Luo, J; Qi, X; Senninger, N; Wang, W; Wang, Y; Xiaoli, F; Xiong, Y; Ye, Q; Ye, S; Zhang, X; Zhong, Z, 2019)	3.4
"Simvastatin treatment mitigated periapical bone loss and reduced the activities of apoptosis and mitophagy in regional osteoblasts."	( Simvastatin alleviates bone resorption in apical periodontitis possibly by inhibition of mitophagy-related osteoblast apoptosis. Chang, JZ; Chen, MH; Hong, CY; Kok, SH; Lai, EH; Lin, SK; Shun, CT; Wang, HW; Yang, CN; Yang, H, 2019)	2.68
"The simvastatin-PRP gel treatment promotes wounded tendon-bone interface healing in clinical treatment."	( Simvastatin With PRP Promotes Chondrogenesis of Bone Marrow Stem Cells In Vitro and Wounded Rat Achilles Tendon-Bone Interface Healing In Vivo. Hua, Y; Yu, J; Zhang, J; Zhang, Y, 2019)	2.44
"In simvastatin-treated C2C12 myotubes, mRNA and protein expression of the insulin receptor (IR) β-chain was increased, but the phosphorylation (Tyr1361) was impaired."	( Mechanisms of insulin resistance by simvastatin in C2C12 myotubes and in mouse skeletal muscle. Bouitbir, J; Krähenbühl, S; Panajatovic, MV; Sanvee, GM, 2019)	1.3
"Simvastatin treatment resulted in up-regulation of IRBP and its upstream transcription factor CRX in Y79 cells, ex vivo human retinal explants, and murine retinas in vivo."	( Simvastatin protects photoreceptors from oxidative stress induced by all-trans-retinal, through the up-regulation of interphotoreceptor retinoid binding protein. Bahrami, B; Gillies, M; Murray, M; Shen, W; Wang, K; Wang, Y; Yao, W; Zeng, S; Zhang, T; Zhou, F; Zhu, L; Zhu, M, 2019)	2.68
"Simvastatin and SimNP treated cells showed significantly greater expression of osteopontin (OPN) and osteocalcin (OCN)."	( Locally Applied Simvastatin as an Adjunct to Promote Spinal Fusion in Rats. Cunningham, ME; Donnelly, PE; Iyer, S; Oh, K; Spaniel, G; Young, K, 2019)	1.58
"Simvastatin treatment was able to significantly reduce hepatic damage enzymes and hepatic lipids and lower the degree of hepatocellular ballooning, without showing genotoxic effects. "	( Simvastatin Reduces Hepatic Oxidative Stress and Endoplasmic Reticulum Stress in Nonalcoholic Steatohepatitis Experimental Model. Bona, S; Di Naso, FC; Dias, AS; Marroni, CA; Marroni, NP; Moreira, AJ; Picada, JN; Pires, TR; Rodrigues, G; Schemitt, E, 2019)	3.4
"Simvastatin treatment in T2D patients selectively reduced serum Ca levels and urinary Mg levels."	( Associations of serum and urinary magnesium with the pre-diabetes, diabetes and diabetic complications in the Chinese Northeast population. Cai, L; Sun, W; Xu, J; Xu, W; Yao, H; Zhou, Q, 2013)	1.11
"Simvastatin-treated patients with AAA exert lower CyPA messenger RNA (mRNA), as well as CyPA intracellular protein levels and a decreased amount of phospho-ERK1/2. "	( Decreased tissue levels of cyclophilin A, a cyclosporine a target and phospho-ERK1/2 in simvastatin patients with abdominal aortic aneurysm. Demyanets, S; Domenig, CM; Huk, I; Klinger, M; Mittlboeck, M; Nanobachvili, J; Neumayer, C; Nykonenko, O; Piechota-Polanczyk, A; Wojta, J, 2013)	2.05
"Simvastatin treatment alone reduced constitutive Cx43 levels and prevented the TNF-α-induced IL-18 up-regulation."	( Simvastatin attenuates the additive effects of TNF-α and IL-18 on the connexin 43 up-regulation and over-proliferation of cultured aortic smooth muscle cells. Chang, LT; Chiang, CH; Chua, S; Chung, SY; Hsieh, MC; Kao, YH; Leu, S; Lin, YC; Shao, PL; Sun, CK; Tsai, TH; Yip, HK, 2013)	2.55
"Simvastatin treatment prevented both skin thickness and pulmonary fibrosis."	( Simvastatin attenuates the development of pulmonary and cutaneous fibrosis in a murine model of systemic sclerosis. Altavilla, D; Bagnato, G; Bitto, A; Cinquegrani, M; Irrera, N; Matucci Cerinic, M; Pizzino, G; Roberts, WN; Saitta, A; Sangari, D; Squadrito, F, 2013)	2.55
"Simvastatin treatment (5 mg/kg/day, i.p.) was applied for three consecutive days, starting 1 day before cadmium administration."	( Simvastatin treatment ameliorates injury of rat testes induced by cadmium toxicity. Albuali, WH; Fouad, AA; Jresat, I, 2013)	2.55
"Simvastatin-treated fibroblasts had a significant decrease in myofibroblast production along with decreased cellular proliferation, migration, and MMP-9 activity but increased caspase 3 activity suggesting increased apoptosis."	( Simvastatin reduces venous stenosis formation in a murine hemodialysis vascular access model. Bhattacharya, S; Janardhanan, R; Kong, H; Leof, EB; Mandrekar, J; Misra, S; Mukhopadhyay, D; Roy, B; Vohra, P; Withers, S; Yang, B, 2013)	2.55
"The simvastatin-treated groups presented reduced body weight and mean BP (trained+simvastatin = 99 ± 2 and sedentary+simvastatin = 107 ± 2 mmHg) compared to the sedentary group (122 ± 1 mmHg)."	( Pleiotropic effects of simvastatin in physically trained ovariectomized rats. Belló-Klein, A; Bernardes, N; Brito, JO; De Angelis, K; Fernandes, TG; Irigoyen, MC; Llesuy, SF, 2013)	1.18
"Simvastatin-treated HL-1 cells exhibited mitochondrial translocation of Parkin and p62/SQSTM1, fission, and mitophagy."	( Mitophagy is required for acute cardioprotection by simvastatin. Andres, AM; Damasco, MV; Gottlieb, RA; Hernandez, G; Huang, C; Lee, P; Ratliff, EP; Sin, J; Thornton, CA, 2014)	1.37
"Simvastatin-treated femurs contained fewer adipocytes and a higher Runx2 expression."	( Local injection of a single dose of simvastatin augments osteoporotic bone mass in ovariectomized rats. Cui, Y; Fu, X; Han, X; Leng, H; Song, C; Tan, J; Yang, N, 2014)	1.4
"Simvastatin treatment led to accumulation of cytosolic LDs within the examined cells, a phenomenon which might contribute to the antiproliferative effects of statins."	( The effect of simvastatin on lipid droplets accumulation in human embryonic kidney cells and pancreatic cancer cells. Böhmer, D; Gbelcová, H; Kolář, M; Laubertová, L; Ruml, T; Strnad, H; Svéda, M; Varga, I; Vítek, L; Zelenka, J, 2013)	2.19
"Simvastatin treatments resulted in decreased cell viabilities in various TNBC cell lines."	( Statin induces inhibition of triple negative breast cancer (TNBC) cells via PI3K pathway. Ahn, JS; Im, YH; Jung, HH; Park, YH, 2013)	1.11
"Simvastatin treatment in T2D patients had no significant effect on serum and urinary copper and zinc."	( Analysis of serum and urinal copper and zinc in Chinese northeast population with the prediabetes or diabetes with and without complications. Cai, L; Liu, G; Tan, Y; Xu, J; Zhou, Q, 2013)	1.11
"Simvastatin treatment reduced systemic inflammation and endothelial dysfunction induced by periodontitis. "	( The effect of simvastatin on systemic inflammation and endothelial dysfunction induced by periodontitis. Costa, TP; Fávero, GM; Fernandes, D; Machado, WM; Mendes, RT; Olchanheski, LR; Otuki, MF; Prestes, AP; Santos, FA; Sordi, R; Vellosa, JC, 2014)	2.21
"Simvastatin treatment, in addition to the improvement on serum lipid profile, may reduce other predictors of cardiovascular events associated with periodontitis."	( The effect of simvastatin on systemic inflammation and endothelial dysfunction induced by periodontitis. Costa, TP; Fávero, GM; Fernandes, D; Machado, WM; Mendes, RT; Olchanheski, LR; Otuki, MF; Prestes, AP; Santos, FA; Sordi, R; Vellosa, JC, 2014)	2.21
"Simvastatin treatment did not have a statistically significant effect on any of the measured parameters. "	( Statins and fibrates do not affect development of spontaneous cartilage damage in STR/Ort mice. Bastiaansen-Jenniskens, YM; Bierma-Zeinstra, SM; Botter, SM; Clockaerts, S; Gierman, LM; Kloppenburg, M; van Osch, GJ; Verhaar, JA; Wei, W; Weinans, H; Zuurmond, AM, 2014)	1.85
"Simvastatin treatment significantly decreased RAGEs expression in ECs from diabetic patients and determined a slight increase in PPAR-γ expression but the latter failed to reach statistical significance."	( Simvastatin attenuates the endothelial pro-thrombotic shift in saphenous vein grafts induced by Advanced glycation endproducts. Barbato, R; Chello, M; Coccia, R; Covino, E; De Marco, F; Di Domenico, F; Lusini, M; Spadaccio, C, 2014)	2.57
"Simvastatin treatment seems to be a beneficial and supporting therapeutic that favors protection against alveolar bone loss in a model of experimental periodontitis in rats."	( Evaluation of the effect of simvastatin on the progression of alveolar bone loss in experimental periodontitis--an animal study. Battistetti, GD; da Costa, KF; Faccioni, DM; Kottwitz, LB; Marconato, J; Marin, CF; Nahsan, FP; Nassar, CA; Nassar, PO; Olegário, J, 2014)	2.14
"Simvastatin treatment resulted in G1 cell cycle arrest, a reduction in the enzymatic activity of HMG-CoA, induction of apoptosis as well as DNA damage and cellular stress."	( Simvastatin, an HMG-CoA reductase inhibitor, exhibits anti-metastatic and anti-tumorigenic effects in endometrial cancer. Bae-Jump, VL; Gehrig, PA; Gilliam, TP; Han, X; Kim, K; Schointuch, MN; Stine, JE; Zhou, C, 2014)	2.57
"Simvastatin treatment significantly reduced total cholesterol, low-density lipoprotein-cholesterol, thiobarbituric acid-reactive substances, high-sensitivity C-reactive protein and Hcy, whereas nitrite levels were increased."	( Homocysteine and nitrite levels are modulated by MTHFR 677C>T polymorphism in obese women treated with simvastatin. Andrade, VL; Eccard, B; Jordão, AA; Sandrim, VC; Sertório, JT; Silva, IF; Silveira, JN; Tanus-Santos, JE; Villela, MP, 2014)	1.34
"Simvastatin treatment reduced myocyte cholesterol, caveolin 3 and caveolar density."	( Caveolin contributes to the modulation of basal and β-adrenoceptor stimulated function of the adult rat ventricular myocyte by simvastatin: a novel pleiotropic effect. Agarwal, SR; Calaghan, S; Harvey, RD; MacDougall, DA; Porter, KE; Pugh, SD, 2014)	1.33
"Simvastatin treatment also decreased the expression of the vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 proteins, as measured in homogenized lung tissues (P<0.05) and human epithelial cells."	( Attenuation of airway inflammation by simvastatin and the implications for asthma treatment: is the jury still out? Lee, SI; Liu, JN; Park, HS; Shin, YS; Suh, DH; Yang, EM, 2014)	1.39
"The simvastatin treatment group was given simvastatin by oral gavage 24 h after surgery."	( Reduced apoptosis after acute myocardial infarction by simvastatin. Long, HB; Luo, KQ; Xu, BC, 2015)	1.15
"Simvastatin treatment also suppressed MMP-9 but not MMP-2 expression in human leukemia U937 and KU812 cells."	( Simvastatin induces NFκB/p65 down-regulation and JNK1/c-Jun/ATF-2 activation, leading to matrix metalloproteinase-9 (MMP-9) but not MMP-2 down-regulation in human leukemia cells. Chang, LS; Chen, YJ, 2014)	2.57
"Simvastatin treatment altered the release of cytokines and trophic factors from microglia, including interleukin-1-β, tumour necrosis factor-α, and brain derived neurotrophic factor in a cholesterol-dependent manner."	( Statin treatment affects cytokine release and phagocytic activity in primary cultured microglia through two separable mechanisms. Churchward, MA; Todd, KG, 2014)	1.12
"Simvastatin treatment enhanced neurological functional recovery after TBI possibly via activation of Notch signaling and increasing neurogenesis in the injured area."	( The effect of simvastatin treatment on proliferation and differentiation of neural stem cells after traumatic brain injury. Cong, D; Huang, Q; Liang, H; Wang, X; Wang, Y; Xie, C; Zhang, X, 2015)	2.22
"Simvastatin-treated rats showed slight but significant decreases in MLI and MAN with a partial reversal of lung function decline (all P < 0.05)."	( Simvastatin mitigates functional and structural impairment of lung and right ventricle in a rat model of cigarette smoke-induced COPD. Jiang, X; Li, Z; Sun, W; Wang, L; Wang, Y; Zhang, L, 2014)	2.57
"Simvastatin treatment effectively reduced total cholesterol and low-density lipoprotein cholesterol, but had little effect on high-density lipoprotein cholesterol. "	( Downregulation of miR-146a, cyclooxygenase-2 and advanced glycation end-products in simvastatin-treated older patients with hyperlipidemia. Jia, BB; Lv, YD; Mao, GX; Wang, GF; Wang, YZ; Yang, ZX; Yu, H, 2016)	2.1
"Simvastatin treatment could inhibit inflammation and senescence-associated genes in older patients with hyperlipidemia, suggesting its application in inflammatory and age-related diseases."	( Downregulation of miR-146a, cyclooxygenase-2 and advanced glycation end-products in simvastatin-treated older patients with hyperlipidemia. Jia, BB; Lv, YD; Mao, GX; Wang, GF; Wang, YZ; Yang, ZX; Yu, H, 2016)	2.1
"Simvastatin treatment in patients with AAAs may influence the concentration of proteases and their inhibitors (TIMPs) in aneurysmal wall tissue and ILTs. "	( The Influence of Simvastatin on NGAL, Matrix Metalloproteinases and Their Tissue Inhibitors in Human Intraluminal Thrombus and Abdominal Aortic Aneurysm Tissue. Demyanets, S; Domenig, CM; Hofmann, M; Huk, I; Klinger, M; Mittlboeck, M; Nanobachvili, J; Neumayer, C; Piechota-Polanczyk, A; Wojta, J, 2015)	2.2
"Simvastatin treatment improved cognitive function and locomotor activity in rats. "	( Modulatory role of simvastatin against aluminium chloride-induced behavioural and biochemical changes in rats. Chamallamudi, MR; John, J; Kumar, N; Mudgal, J; Nampoothiri, M; Nampurath, GK, 2015)	2.19
"Simvastatin-treated patients experienced significantly more reductions in HDRS scores compared to the placebo group by the end of the trial (p=0.02)."	( Simvastatin as an adjuvant therapy to fluoxetine in patients with moderate to severe major depression: A double-blind placebo-controlled trial. Akhondzadeh, S; Farokhnia, M; Gougol, A; Iranpour, N; Raheb, S; Salimi, S; Yekehtaz, H; Zareh-Mohammadi, N, 2015)	2.58
"Simvastatin-treated cells and controls were directly assayed by CFSE (Carboxyfluorescein diacetate succinimidyl ester) staining to assess their cell proliferation and their RNA was used for microarray analyses and quantitative PCR (qPCR)."	( Simvastatin modulates mesenchymal stromal cell proliferation and gene expression. Dos Santos, DF; Lorenzi, JC; Palma, PV; Panepucci, RA; Prata, KL; Silva, WA; Zanette, DL, 2015)	2.58
"The simvastatin treatment group was intraperitoneally administered simvastatin (5 mg/kg, 2.0 μL) at 1 h before, and daily for 14 days after surgery, while the sham-operated and LPS-model groups received saline."	( Effects of simvastatin on the expression of inducible nitric oxide synthase and brain-derived neurotrophic factor in a lipopolysaccharide-induced rat model of Parkinson disease. Bei-sha, T; Pei-pei, H; Tan, W; Tian, Z; Xiao-wu, C; Xue-bin, C; Zhi-bin, C, 2016)	1.31
"In simvastatin-treated murine xenografts, ABCB1 was also reduced in the liver and rhabdomyosarcoma but did not reach significance in neuroblastoma."	( In vitro and in vivo downregulation of the ATP binding cassette transporter B1 by the HMG-CoA reductase inhibitor simvastatin. Atil, B; Bardy, J; Berger-Sieczkowski, E; Hohenegger, M; Werner, M, 2016)	1.16
"Simvastatin treatment induced apoptosis in human cybrid prostate cancer cells. "	( A mitochondrial DNA mutation influences the apoptotic effect of statins on prostate cancer. Arnold, RS; Petros, JA; Sun, CQ; Sun, Q, 2015)	1.86
"Simvastatin treatment promotes EAE clinical amelioration by inhibiting T cell proliferation and CNS infiltration by pathogenic Th1 and Th17 cells."	( Simvastatin ameliorates experimental autoimmune encephalomyelitis by inhibiting Th1/Th17 response and cellular infiltration. Câmara, NO; Cenedeze, MA; de Oliveira, DM; de Oliveira, EM; Ferrari, Mde F; Hiyane, MI; Pacheco-Silva, A; Peron, JP; Semedo, P, 2015)	3.3
"In simvastatin-treated H1975 cells, expression of pro-apoptotic proteins was increased and the phosphorylation of ERK 1/2 (p-ERK 1/2) was reduced."	( The apoptotic effect of simvastatin via the upregulation of BIM in nonsmall cell lung cancer cells. Kang, HH; Kim, IK; Lee, HI; Lee, HY; Lee, SH; Mo, JY; Moon, HS; Yeo, CD, 2016)	1.26
"The simvastatin group was pre-treated with simvastatin, whereas the control and sepsis groups were treated with saline before LPS treatment."	( Effects of simvastatin on the expression of inducible NOS in acute lung injury in septic rats. Chen, L; He, ZJ; Li, WC; Zheng, YK; Zhou, L; Zhou, MG; Zou, ZJ, 2015)	1.29
"Simvastatin-treated groups received 50 mg/kg/day simvastatin for 30 days."	( Structural effects of simvastatin on liver rat [corrected] tissue: Fourier transform infrared and Raman microspectroscopic studies. Abbas, S; Bayari, SH; Garip, S; Lednev, IK; Severcan, F; Severcan, M, 2016)	1.47
"Simvastatin treatment results in a significant dose-dependent decrease of SG neurite number, length of neurites, area of supporting cells, and SG neuronal survival compared to control."	( Simvastatin Results in a Dose-Dependent Toxic Effect on Spiral Ganglion Neurons in an In Vitro Organotypic Culture Assay. Bodmer, D; Brand, Y; Egloff, S; Glutz, A; Leitmeyer, K; Setz, C; Wieland, L, 2016)	2.6
"Simvastatin pretreatment decreased mRNA expression of caspase-3 and -9, and RIPK1 and -3 and protein activity of caspase-9 and RIPK1 in the allografts."	( Simvastatin pretreatment reduces caspase-9 and RIPK1 protein activity in rat cardiac allograft ischemia-reperfusion. Holmström, E; Krebs, R; Lemström, KB; Raissadati, A; Rouvinen, E; Saharinen, P; Tuuminen, R, 2016)	2.6
"Simvastatin treated cells did exhibit a reduced height-to-width aspect ratio and these changes in cell morphology resulted in a significant decrease in epithelial cell injury during airway reopening."	( Simvastatin Treatment Modulates Mechanically-Induced Injury and Inflammation in Respiratory Epithelial Cells. Ghadiali, SN; Higuita-Castro, N; Mihai, C; Shukla, VC, 2016)	2.6
"Simvastatin treatment was found to induce type II collagen expression and sulfated-proteoglycan synthesis in a dose- and time-dependent manner."	( Simvastatin induces differentiation of rabbit articular chondrocytes via the ERK-1/2 and p38 kinase pathways. Han, Y; Kim, SJ, 2016)	2.6
"Simvastatin treatment did not modify the plasma lipid levels; however, it recovered depressed cardiac performance and reduced reperfusion arrhythmias without affecting the activation of CaMKIIδ through phosphorylation of Thr287. "	( Pleiotropic Effects of Simvastatin on Some Calcium Regulatory and Myofibrillar Proteins in Ischemic/Reperfused Heart: Causality of Statins Cardioprotection? Adameova, A; Carnicka, S; Lichy, M; Pancza, D; Ravingerova, T; Svec, P; Szobi, A, 2016)	2.19
"Simvastatin treatment inhibited IL-13 transcription in a dose-dependent manner, and therefore diminished the IL-13-induced increase in OPN and restored IL-13-suppressed ADA."	( Simvastatin up-regulates adenosine deaminase and suppresses osteopontin expression in COPD patients through an IL-13-dependent mechanism. Barnes, PJ; Kasetsinsombat, K; Maneechotesuwan, K; Wongkajornsilp, A, 2016)	2.6
"Simvastatin treatment did not reduce normal serum cholesterol or lipid levels in these mice, suggesting that the longevity effects may stem from the pleiotropic, non-cholesterol-related, effects of statins."	( Combined statin and angiotensin-converting enzyme (ACE) inhibitor treatment increases the lifespan of long-lived F1 male mice. Flegal, JM; Mote, PL; Spindler, SR, 2016)	1.16
"Simvastatin pretreatment reduced endothelial tube formation in vitro and microvessel density in vivo."	( Simvastatin inhibits tumor angiogenesis in HER2-overexpressing human colorectal cancer. Li, G; Ling, J; Qiu, W; Wang, Y; Xu, B; Zheng, J, 2017)	2.62
"Simvastatin treatment reduces the levels of glucose, lipid, leptin and neutrophil percentage, and improves airway inflammation and remodeling, which can be as a potential therapeutic target used in the treatment of obese asthma in humans."	( Treatment of obese asthma in a mouse model by simvastatin is associated with improving dyslipidemia and decreasing leptin level. Han, W; Li, J; Sun, L; Tang, H, 2017)	1.43
"Simvastatin treatment for 35 days, at a dose having no significant effect on plasma lipid levels, significantly reduced atherosclerotic progression as evident by reduced macrophage content, inflammatory burden, and extracellular matrix component like proteoglycans and metalloproteinase-9."	( Progression and Characterization of the Accelerated Atherosclerosis in Iliac Artery of New Zealand White Rabbits: Effect of Simvastatin. Barthwal, MK; Dikshit, M; Farooqui, M; Jain, M; Kanshana, JS; Khanna, V; Kumar, S; Misra, A; Singh, V, 2017)	1.38
"Simvastatin treatment for 35 days exhibited anti-atherosclerotic efficacy without significantly lowering the circulating lipids."	( Progression and Characterization of the Accelerated Atherosclerosis in Iliac Artery of New Zealand White Rabbits: Effect of Simvastatin. Barthwal, MK; Dikshit, M; Farooqui, M; Jain, M; Kanshana, JS; Khanna, V; Kumar, S; Misra, A; Singh, V, 2017)	1.38
"Simvastatin treatment did not change plasma cholesterol levels or modify the adrenal expression levels of genes involved in cholesterol metabolism. "	( Simvastatin treatment aggravates the glucocorticoid insufficiency associated with hypocholesterolemia in mice. Hoekstra, M; Nahon, JE; Ouweneel, AB; van der Sluis, RJ; Van Eck, M, 2017)	3.34
"Simvastatin treatment significantly increased EPC in the hypercholesterolemic group, but failed to improve the EPC levels in the SSc patients, mainly in patients with late disease. "	( Simvastatin reduces endothelial activation and damage but is partially ineffective in inducing endothelial repair in systemic sclerosis. Comina, DP; Cortelezzi, A; Cortiana, M; Del Papa, N; Lucchi, T; Maglione, W; Silvestris, I; Vitali, C, 2008)	3.23
"Simvastatin treatment significantly decreased blood-brain barrier (BBB) leakage and concomitantly, increased Ang1, Tie2 and Occludin expression in the ischaemic border (IBZ) compared to the MCAo control group."	( Increasing Ang1/Tie2 expression by simvastatin treatment induces vascular stabilization and neuroblast migration after stroke. Chen, J; Chopp, M; Cui, X; Zacharek, A, 2009)	1.35
"Simvastatin treatment significantly increased the number of peripheral blood CD34+ CD133+ cells, and serum concentration of vascular endothelial growth factor (VEGF) and AKT was markedly increased in vivo."	( HMG-CoA reductase inhibitor regulates endothelial progenitor function through the phosphatidylinositol 3'-kinase/AKT signal transduction pathway. Li, X; Xu, B, 2009)	1.07
"Both simvastatin and losartan treatment significantly reversed the effects of DM on integrity of Cx43 expression."	( Diabetes mellitus downregulates expression of connexin43 in rat aortic medial smooth muscle cells and can be reversed by simvastatin and losartan therapy. Chang, LT; Chang, NK; Chiang, CH; Sheu, JJ; Sun, CK; Tsai, TH; Yip, HK; Youssef, AA, )	0.79
"Simvastatin or placebo treatment once daily for 12 weeks."	( Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: a randomized controlled trial. Aarsen, FK; Arts, WF; Bouman, MJ; Catsman, CE; de Goede-Bolder, A; de Zeeuw, CI; Elgersma, Y; Krab, LC; Kushner, SA; Lequin, M; Moll, HA; Pluijm, SM; Silva, AJ; van der Geest, JN, 2008)	2.19
"Simvastatin treatment for 4 weeks significantly improved FMD and reduced low density LDL-C and total TC levels. "	( [The effects of simvastatin withdrawal on brachial artery endothelial function in healthy normocholesterolemic men]. Chen, H; Liu, X; Qiao, ZG; Ren, JY; Wu, B; Zhang, FF, 2008)	2.13
"Simvastatin treatment was found to activate protein kinase B (PKB)/c-akt, a primary effector of PI3K, and ectopic expression of constitutively active PKB was sufficient to induce IL-1beta release."	( HMG-CoA reductase inhibition induces IL-1beta release through Rac1/PI3K/PKB-dependent caspase-1 activation. Beekman, JM; Coffer, PJ; Frenkel, J; Koster, J; Kuijk, LM; Waterham, HR, 2008)	1.07
"In simvastatin-treated animals, CSPG levels declined by 60% 8 days after brain stab injury, and by 62-64% 4 weeks after spinal cord injury (SCI)."	( Statins decrease chondroitin sulfate proteoglycan expression and acute astrocyte activation in central nervous system injury. Doolen, S; Holmberg, E; Kluge, BR; Sarmiere, PD; White, JT; Zhang, SX, 2008)	0.86
"Simvastatin treatment is associated with moderate clinical improvement in patients with active RA. "	( Changes in disease activity, cytokine production, and proliferation of peripheral blood mononuclear cells in patients with rheumatoid arthritis after simvastatin treatment. Kozlov, VA; Shirinsky, IV; Shirinsky, VS; Solovyova, NY; Zheltova, OI, )	1.77
"simvastatin treatment significantly increased arterial cell migration compared to control MCAo artery, whereas inhibition of Notch signaling activity by the gamma40-secretase inhibitor II significantly attenuated simvastatin-induced arterial cell migration."	( Simvastatin increases notch signaling activity and promotes arteriogenesis after stroke. Chen, J; Chopp, M; Cui, X; Yang, Y; Zacharek, A, 2009)	2.52
"In simvastatin-treated patients, changes in LDL cholesterol related negatively to changes in M (r = -0.796, P < 0.01)."	( Effects of high-dose simvastatin therapy on glucose metabolism and ectopic lipid deposition in nonobese type 2 diabetic patients. Anderwald, C; Bayerle-Eder, M; Brehm, A; Esterbauer, H; Hofer, A; Krssak, M; Nowotny, P; Pfeiler, G; Roden, M; Szendroedi, J; Waldhäusl, W, 2009)	1.19
"Simvastatin treatment resulted in a marked reduction of T and B cells in spleen, lymph nodes and peripheral blood in mice."	( Simvastatin impairs humoral and cell-mediated immunity in mice by inhibiting lymphocyte homing, T-cell activation and antigen cross-presentation. Baldari, CT; Benati, D; Fanigliulo, D; Pasini, FL; Ulivieri, C, 2008)	2.51
"Simvastatin treatment significantly altered nodule morphology, resulting in dramatic nodule dissipation over time, also in a substrate-dependent manner."	( Efficacy of simvastatin treatment of valvular interstitial cells varies with the extracellular environment. Gu, X; Masters, KS; Monzack, EL, 2009)	1.45
"In simvastatin treated I/R rats we had increase in functional recovery."	( The effects of simvastatin on functional recovery of rat reperfused sciatic nerve. Abolhassani, F; Akbari, M; Gholami, MR; Mehrania, K; Pasbakhsh, P; Sobhani, A; Sohrabi, D, 2007)	1.21
"Simvastatin treatment in diabetic rats, in addition to the treatment of diabetic dislipidemia, has also partially treated the endothel-mediated releasing response in diabetes. "	( Vascular reactivity in the experimental, simvastatin-treated diabetes with endothelial dysfunction. Demirel, E; Ergül, E; Köksoy, C; Yalcin, B; Yalcin, S, 2008)	2.05
"Oral simvastatin treatment (10-20 mg kg(-1) day(-1)) increased bone volume and osteoblast number in the distal femurs, proximal tibiae and vertebrae of OVX rats."	( Simvastatin increases osteoblasts and osteogenic proteins in ovariectomized rats. Chang, JK; Chen, CH; Chen, YH; Fu, YC; Ho, ML; Hung, SH; Lee, MJ; Liao, HJ; Wang, GJ; Wang, YH, 2009)	2.25
"Simvastatin treatment induced an increase in autoantibodies against an oxLDL antigen."	( Effects of simvastatin on circulating autoantibodies to oxidized LDL antigens: relation with immune stimulation markers. Cherfan, P; Gonçalves, I; Jonasson, L; Nordin Fredrikson, G; Söderberg, I, 2009)	1.46
"Simvastatin treatment of mice led to a significant increase in AMPK and LKB1 phosphorylation and to a decrease in protein kinase A activity relative to control animals, associated with a marked increase in Rac1 activation."	( Regulation of Rac1 by simvastatin in endothelial cells: differential roles of AMP-activated protein kinase and calmodulin-dependent kinase kinase-beta. Kou, R; Michel, T; Sartoretto, J, 2009)	1.39
"Simvastatin treatment (weeks 4 to 6) caused a decrease in myelin load and both Olig2(strong) and Nkx2.2(strong) OPC numbers."	( Statin therapy inhibits remyelination in the central nervous system. Antel, JP; Bedell, BJ; Kennedy, TE; Kuhlmann, T; Ludwin, SK; Miron, VE; Owens, T; Zehntner, SP, 2009)	1.07
"Simvastatin pretreatment inhibited TGF-beta1-mediated phosphorylation of smad-3."	( Simvastatin impairs smad-3 phosphorylation and modulates transforming growth factor beta1-mediated activation of intestinal fibroblasts. Burke, JP; Coffey, JC; Docherty, NG; Murphy, M; O'Connell, PR; Watson, RW, 2009)	2.52
"In simvastatin-treated subjects (n = 9) significant reductions of PAI-1 were achieved (p = 0.028), while sCD40L and TAFI-Ag did not differ from baseline values."	( Soluble CD40 ligand, plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor-1-antigen in normotensive type 2 diabetic subjects without diabetic complications. Effects of metformin and rosiglitazone. Akinci, B; Bayraktar, F; Comlekci, A; Demir, T; Ozcan, MA; Yener, S; Yesil, S; Yuksel, F, 2009)	0.87
"The simvastatin-treated group showed lower serum lipid levels than the tongxinluo-treated group."	( Chinese medicine tongxinluo significantly lowers serum lipid levels and stabilizes vulnerable plaques in a rabbit model. Chen, WQ; Ji, XP; Jiang, H; Wu, YL; Zhang, C; Zhang, L; Zhang, Y; Zhao, YX; Zhong, L, 2009)	0.83
"Simvastatin treatment of 1.0 mg/kg increased the number of morphologically intact neurons in the hippocampus, but treatment of 0.5 mg/kg had no significant effect."	( Long-term benefits after treatment of traumatic brain injury with simvastatin in rats. Chopp, M; Goussev, A; Kazmi, H; Lu, D; Mahmood, A; Qu, C, 2009)	1.31
"Simvastatin treatment provides long-lasting functional improvement after TBI in rats. "	( Long-term benefits after treatment of traumatic brain injury with simvastatin in rats. Chopp, M; Goussev, A; Kazmi, H; Lu, D; Mahmood, A; Qu, C, 2009)	2.03
"Simvastatin treatment leads to a significant decrease in malondealdehyde levels (p < 0.05) and increase in paraoxonase activity (p < 0.001) at both time points."	( Simvastatin improves wound strength after intestinal anastomosis in the rat. Acikgoz, S; Ankarali, H; Bahadir, B; Comert, M; Demirtas, C; Emre, AU; Irkorucu, O; Karadeniz Cakmak, G; Karakaya, K; Kertis, G; Pasaoglu, H; Tascilar, O; Ucan, BH, 2009)	2.52
"Simvastatin treatment before methacholine bronchial challenge increased lung compliance and reduced airway hyperreactivity (P = 0.0001)."	( Simvastatin inhibits airway hyperreactivity: implications for the mevalonate pathway and beyond. Franzi, L; Kenyon, NJ; Last, J; Zeki, AA, 2009)	2.52
"Simvastatin pretreatment reduced the LPS-induced increase in serum levels of ALT by 65% in hepatectomized animals."	( Simvastatin attenuates hepatic sensitization to lipopolysaccharide after partial hepatectomy. Jeppsson, B; Laschke, MW; Menger, MD; Schilling, MK; Slotta, JE; Thorlacius, H, 2010)	2.52
"Simvastatin treatment partly prevented atherosclerotic changes induced by ovariectomy."	( Antiatherogenic effect of simvastatin is not due to decrease of LDL cholesterol in ovariectomized golden Syrian hamster. Bobková, D; Havlíčková, J; Kovář, J; Pitha, J; Poledne, R, 2010)	1.38
"Simvastatin pretreatment reduced intestinal I/R injury and was associated with down- -regulation of serum TNF-alpha and tissue malondealdehyde level, and simvastatin administration maintained cellular antioxidant enzyme contents compared to the I/R group after 3 hours reperfusion time."	( Simvastatin attenuates intestinal ischemia/reperfusion induced injury in rat. Asl, NA; Hajipour, B; Hemmati, MR; Moein, A; Nasirizade, MR; Nourazar, AR; Saberifar, F; Somi, MH; Vatankhah, AM, 2009)	2.52
"Simvastatin treatment significantly decreased tPA-induced hemorrhage incidence (p=0.022) and volume (p=0.0001) following embolization."	( The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin reduces thrombolytic-induced intracerebral hemorrhage in embolized rabbits. Han, MK; Lapchak, PA, 2009)	1.31
"Simvastatin treatment was superior to metformin alone, whereas a combination of simvastatin and metformin was not significantly superior to simvastatin alone."	( Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial. Banaszewska, B; Duleba, AJ; Pawelczyk, L; Spaczynski, RZ, 2009)	2.16
"Simvastatin pretreatment given orally produced acute anti-inflammatory effects by inhibiting TNF-alpha and IL-1beta, but no IL-6 production."	( Effect of simvastatin on proinflammatory cytokines production during lipopolysaccharide-induced inflammation in rats. Dobrić, S; Milovanović, ZA; Nezić, L; Satara, SS; Skrbić, R; Stojaković, N; Stojiljković, MP, 2009)	1.48
"Simvastatin pretreatment increased survival after H/R from 20% to 80%."	( Simvastatin reduces mortality and hepatic injury after hemorrhage/resuscitation in rats. Bormann, F; Czerny, C; Henrich, D; Höhn, C; Lehnert, M; Marzi, I; Relja, B; Seyboth, K, 2010)	2.52
"Simvastatin treatment similarly did not affect total ubiquinone levels in the myotubes, unlike in HepG2 cells (22% reduction in CoQ10)."	( Effect of simvastatin on cholesterol metabolism in C2C12 myotubes and HepG2 cells, and consequences for statin-induced myopathy. Brecht, K; Krähenbühl, S; Lüscher, B; Mullen, PJ; Scharnagl, H, 2010)	1.48
"Simvastatin-treated hearts exhibited smaller size of infarction (11.5% +/- 0.4% vs."	( Changes in PPAR gene expression and myocardial tolerance to ischaemia: relevance to pleiotropic effects of statins. Adameová, A; Antonopoulou, E; Carnická, S; Kelly, T; Khandelwal, VK; Lazou, A; Ondrejcáková, M; Pancza, D; Ravingerová, T, 2009)	1.07
"Simvastatin treatment down-regulated the formation of microclots in this SAH model and the number of microthombi was decreased significantly in the SAH+simvastatin group compared to the SAH or SAH+vehicle groups (p <0.01)."	( Influence of simvastatin on microthrombosis in the brain after subarachnoid hemorrhage in rats: a preliminary study. Bian, JY; Chen, G; Shen, XO; Wang, Z; Zhou, D; Zhu, WW, 2010)	1.45
"Simvastatin treatment significantly reduced the thickness of the intima and media aorta and increased vasa vasorum density in comparison with those in hyperlipidemic group."	( [Effects of simvastatin on vasa vasorum and aortic endothelial function in rats]. Chen, MS; He, ZC; Lu, DF; Wang, W; Wu, J; Xiao, Y, 2010)	1.46
"Simvastatin treatment greatly increased the densities of MBP immunostaining, inhibited microglial activation and reduced the numbers of pyknotic cells and neuronal loss."	( Simvastatin attenuates hypomyelination induced by hypoxia-ischemia in neonatal rats. Li, A; Li, S; Lv, S; Ma, H; Piao, H; Sun, C; Yu, Z; Zhang, N; Zhang, Y; Zhao, H, 2010)	2.52
"Simvastatin treatment caused a decrease in epithelial iNOS levels, while MPO levels were not modulated."	( Protective role of simvastatin on lung damage caused by burn and cotton smoke inhalation in rats. Basaran, O; Belli, S; Haberal, M; Karabay, G; Karakayali, H; Kut, A; Ozdemir, BH; Türkoğlu, S, 2011)	1.42
"Simvastatin treatment resulted in a decrease in the number of cancer cells (3LL, A549 and NCI-H292)."	( Immune regulatory effects of simvastatin on regulatory T cell-mediated tumour immune tolerance. Choi, HK; Hur, GY; In, KH; Jung, KH; Kang, KH; Kim, HO; Kim, JH; Lee, KJ; Lee, SY; Moon, JY; Shim, JJ; Shin, C; Yoo, SH, 2010)	1.37
"Simvastatin treatment (20mg/kg, bolus subcutaneous injection) significantly improved clinical function and increased the P(50) by 143% when administered 1 hour following embolization but was ineffective at 3 hours."	( Simvastatin improves clinical scores in a rabbit multiple infarct ischemic stroke model: synergism with a ROCK inhibitor but not the thrombolytic tissue plasminogen activator. Han, MK; Lapchak, PA, 2010)	2.52
"Simvastatin treatment significantly reduced C-reactive protein (CRP) levels while interleukin (IL)-6 levels remained unchanged."	( Effects of simvastatin on proinflammatory cytokines and matrix metalloproteinases in hypercholesterolemic individuals. Cherfan, P; Eriksson, P; Jonasson, L; Nilsson, L, 2011)	1.48
"Simvastatin treatment limited pulmonary endothelial injury, attenuated pulmonary hyperpermeability, prevented the recruitment of leukocytes to the lung, reduced pulmonary cytokine levels and improved oxygenation in mechanically ventilated mice."	( Simvastatin attenuates ventilator-induced lung injury in mice. Gutbier, B; Hellwig, K; Hippenstiel, S; Morawietz, L; Müller, HC; Peters, H; Rosseau, S; Schmeck, B; Schmiedl, A; Suttorp, N; Tschernig, T; Witzenrath, M, 2010)	2.52
"Simvastatin treatment prevented Aβ-induced production of IFN-γ in splenocytes."	( Simvastatin enhances immune responses to Aβ vaccination and attenuates vaccination-induced behavioral alterations. Cao, D; Fukuchi, K; Jin, J; Kim, HD; Kou, J; Lalonde, R; Li, L, 2010)	2.52
"Simvastatin treatment blocked hyperglycemia-induced increases in VEGF, angiopoietin 2 and erythropoietin levels, as demonstrated by RT-PCR and Western blot analysis."	( Simvastatin suppresses expression of angiogenic factors in the retinas of rats with streptozotocin-induced diabetes. Hur, DY; Kim, HW; Kim, JL; Lee, HK; Lee, SG; Ryu, GW; Yang, JW; Yun, IH, 2011)	2.53
"Simvastatin treatment led to suppression of superoxide formation and decreased expression of VEGF, angiopoietin 2 and erythropoietin in diabetic rat retinas."	( Simvastatin suppresses expression of angiogenic factors in the retinas of rats with streptozotocin-induced diabetes. Hur, DY; Kim, HW; Kim, JL; Lee, HK; Lee, SG; Ryu, GW; Yang, JW; Yun, IH, 2011)	3.25
"The simvastatin treatment group showed significantly reduced LV wall thickness, myocardial cell diameters and LV collagen content at 40 weeks when compared with the control group (P<0.05)."	( Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a "Western-style diet" by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels. Du, J; He, JQ; Qin, YW; Sheng, L; Wang, LY; Ye, P, 2010)	2.28
"Simvastatin treatment resulted in significant reductions in serum lipid levels at 3 months and beyond, compared to at baseline. "	( Effects of simvastatin on markers of inflammation, oxidative stress and endothelial cell apoptosis in patients on chronic hemodialysis. Alexopoulos, E; Belechri, AM; Dogrammatzi, F; Efstratiadis, G; Kirmizis, D; Memmos, D; Papagianni, A; Skoura, L, 2010)	2.19
"Simvastatin treatment in MCT-PH rats not only attenuated pulmonary hypertension, but also desensitized PCF hypersensitivity and decreased the production of ROS. "	( Effects of simvastatin on pulmonary C-fiber sensitivity in rats with monocrotaline-induced pulmonary hypertension. Chen, CF; Chen, JS; Hsu, HH; Hsu, JY; Ko, WJ; Lai, IR; Lee, YC; Ruan, T, 2011)	2.2
"Simvastatin-ezetimibe treatment was not associated with a statistically significant reduction in AVEs in any individual tertile."	( Impact of baseline severity of aortic valve stenosis on effect of intensive lipid lowering therapy (from the SEAS study). Boman, K; Brudi, P; Chambers, JB; Egstrup, K; Gerdts, E; Gohlke-Bärwolf, C; Holme, I; Kesäniemi, YA; Malbecq, W; Nienaber, C; Pedersen, TR; Ray, S; Rossebø, AB; Skjærpe, T; Wachtell, K; Willenheimer, R, 2010)	1.08
"Simvastatin treatment inhibited dose-dependently tumor cell growth and attachment to endothelium."	( Simvastatin modulates the adhesion and growth of hepatocellular carcinoma cells via decrease of integrin expression and ROCK. Blaheta, R; Henrich, D; Lehnert, M; Marzi, I; Meder, F; Relja, B; Wang, M, 2011)	2.53
"Simvastatin treatment also resulted in a proteasome-sensitive reduction in the protein expression of all the subunits of the eIF2B heteropentameric complex."	( Simvastatin represses protein synthesis in the muscle-derived C₂C₁₂ cell line with a concomitant reduction in eukaryotic initiation factor 2B expression. Jefferson, LS; Jefferson, SJ; Kimball, SR; Tuckow, AP, 2011)	2.53
"Simvastatin pre-treatment also prevented the increase in eNOS monomer formation that was associated with SAH, decreased superoxide anion radical production and increased NO."	( Simvastatin re-couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage. Ai, J; Macdonald, RL; Marsden, PA; Sabri, M, 2011)	2.53
"Simvastatin-treated cells displayed an altered lamellipodia with poorly developed focal adhesion contacts and reduced levels of β1 integrin activation."	( Simvastatin alters fibroblastic cell responses involved in tissue repair. Cáceres, M; Copaja, M; Díaz-Araya, G; Martínez, J; Romero, A; Smith, PC, 2011)	2.53
"Simvastatin treatment to I+G mice attenuated their cardiac apoptosis, iron deposition, and abrogated thrombus formation by attenuating systemic inflammation and leukocytosis, which was likely due to the activation of pAKT activation."	( Granulocyte-CSF induced inflammation-associated cardiac thrombosis in iron loading mouse heart and can be attenuated by statin therapy. Cheng, CF; Cheng, WT; Kikuchi, T; Lian, WS; Lin, H, 2011)	1.09
"Simvastatin in both treated groups significantly decreased serum levels of triacylglycerols and VLDL-cholesterol in comparison to the control animals."	( Antineoplastic effects of simvastatin in experimental breast cancer. Bojková, B; Kajo, K; Kassayová, M; Kubatka, P; Orendás, P; Péc, M; Stollárová, N; Zihlavniková, K, 2011)	1.39
"Simvastatin treatment can attenuate hindlimb motor dysfunction and histopathological changes in spinal cord ischemia/reperfusion injury in rats."	( Reduction of spinal cord ischemia/reperfusion injury with simvastatin in rats. Hayashi, J; Kohno, T; Saito, T; Tsuchida, M; Umehara, S; Yamamoto, H, 2011)	2.06
"Simvastatin treatment significantly down-regulated the percentage of MMP-3 expression in chondrocytes as assessed by immunohistochemistry methods. "	( Mechanically induced experimental knee osteoarthritis benefits from anti-inflammatory and immunomodulatory properties of simvastatin via inhibition of matrix metalloproteinase-3. Aktas, E; Gocun, PU; Sener, E, 2011)	2.02
"Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles."	( Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin. Bumbasirevic, V; Harhaji-Trajkovic, L; Janjetovic, K; Micic, D; Misirkic, M; Ristic, B; Sumarac-Dumanovic, M; Tovilovic, G; Trajkovic, V; Vilimanovich, U; Vucicevic, L, 2012)	1.33
"In simvastatin-treated patients (n = 57), the dose was increased to 80 mg in five patients who had not attained the National Cholesterol Education Program (NCEP) target for low-density lipoprotein cholesterol (LDL-C) during the core study."	( Long-term efficacy of pitavastatin versus simvastatin. Budinski, D; Eriksson, M; Hounslow, N, 2011)	1.15
"Simvastatin treatment (5 mg/kg/day for 2 wks) was performed by gavage."	( Simvastatin-induced cardiac autonomic control improvement in fructose-fed female rats. Bernardes, N; Brito, Jde O; De Angelis, K; Irigoyen, MC; Sanches, IC; Silva, RJ, 2011)	2.53
"Simvastatin treatment improved insulin sensitivity and cardiac autonomic control in an experimental model of metabolic syndrome in female rats. "	( Simvastatin-induced cardiac autonomic control improvement in fructose-fed female rats. Bernardes, N; Brito, Jde O; De Angelis, K; Irigoyen, MC; Sanches, IC; Silva, RJ, 2011)	3.25
"Simvastatin treatment does not influence Gα(s) protein stability, and paradoxically increases the abundance of Gα(s) mRNA."	( Suppression of Gαs synthesis by simvastatin treatment of vascular endothelial cells. Kou, R; Michel, T; Sartoretto, JL; Shiroto, T, 2012)	1.38
"Simvastatin treatment of hypercholesterolemic mice and monkeys reduced oxLDL, monocyte TF expression, MP TF activity, activation of coagulation, and inflammation, without affecting total cholesterol levels."	( Monocyte tissue factor-dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin. Antoniak, S; Curtiss, LK; Daugherty, A; Dutton, JA; Furie, B; Furie, BC; Hubbard, BK; Johns, DG; Kirchhofer, D; Luyendyk, JP; Mackman, N; Marshall, SM; McDaniel, AL; Moriarty, PM; Nagarajan, S; Owens, AP; Passam, FH; Rudel, L; Temel, RE; Tobias, PS; Wang, J; Williams, JC, 2012)	1.31
"Simvastatin treatment with doses ranging from 0.5 to 20 mg/kg/day significantly enhanced early epithelial recovery and reduced the development of OAD. "	( Effect of simvastatin on development of obliterative airway disease: an experimental study. Hollmén, M; Keränen, MA; Krebs, R; Lemström, KB; Nykänen, AI; Ropponen, JO; Syrjälä, SO; Tikkanen, JM; Tuuminen, R; Vaali, K, 2012)	2.22
"Simvastatin treatment inhibited adaptive T-cell alloimmune activation as depicted by reduced expression of lymphocyte chemokine and pro-inflammatory cytokine mRNA and reduced allograft infiltration by inflammatory cells. "	( Effect of simvastatin on development of obliterative airway disease: an experimental study. Hollmén, M; Keränen, MA; Krebs, R; Lemström, KB; Nykänen, AI; Ropponen, JO; Syrjälä, SO; Tikkanen, JM; Tuuminen, R; Vaali, K, 2012)	2.22
"Simvastatin treatment did not alter the activation status of iNKT cells as measured by HLA-DR expression."	( Statin-induced immunomodulation alters peripheral invariant natural killer T-cell prevalence in hyperlipidemic patients. Babageorgakas, P; Bouchliou, I; Kotsianidis, I; Margaritis, D; Miltiades, P; Nakou, E; Spanoudakis, E; Stakos, DA; Tziakas, DN, 2012)	1.1
"Simvastatin treatment resulted in a statistically signuficant decrease of the IMT thickness of the right common carotid artery. "	( [Simvastatin influence on carotid atherosclerotic disease regression]. Davidović, L; Radmili, O; Vasić, D; Vraneš, M, )	2.48
"Simvastatin-treated animals showed significantly better locomotor recovery, less signal abnormality in MRI and a smaller cavity volume compared to the control group."	( Simvastatin mobilizes bone marrow stromal cells migrating to injured areas and promotes functional recovery after spinal cord injury in the rat. Cui, Y; Dang, G; Han, X; Song, C; Xu, Y; Yang, N, 2012)	2.54
"Simvastatin treatment before and after onset of ALI reduces neutrophil influx into the lung as well as lung permeability indicating the protective role of simvastatin in ALI. "	( Simvastatin reduces endotoxin-induced acute lung injury by decreasing neutrophil recruitment and radical formation. Binnebösel, M; Dembinski, R; Drechsler, M; Grommes, J; Hartwig, H; Jacobs, M; Koeppel, TA; Mörgelin, M; Soehnlein, O; Vijayan, S; Weber, C, 2012)	3.26
"Simvastatin-treated subjects were separated according to their median creatine kinase (CK) increase."	( Effect of a high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers. Chevassus, H; Costa, F; Cristol, JP; Dupuy, A; Farret, A; Gagnol, JP; Galtier, F; Lacampagne, A; Mercier, J; Mura, T; Petit, P; Raynaud de Mauverger, E, 2012)	1.4
"Simvastatin treatment activated free radical oxidation, which was seen from enhanced chemiluminescence in the mucosa homogenate (by 1.7-4.6 times)."	( Effect of HMG-CoA-reductase inhibitor on DNA synthesis and free radical oxidation in the gastric mucosa under normal conditions and during indometacin-induced ulcerative process in the stomach of albino mice. Bragina, VV; Fleischman, MY; Lebedko, OA; Sazonova, EN; Timoshin, SS; Zhivotova, EY, 2012)	1.1
"Simvastatin, treatment significantly improved all of these parameters in model rats (vs."	( [Simvastatin inhibits activation of hepatic stellate cells and promotes activation of adenosine monophosphate-activated protein kinase]. Cao, W; Wang, W; Yan, L; Zhao, CY, 2012)	2.01
"Simvastatin treatment also reduced umbilical vein endothelial cell aging and increased SIRT1 expression."	( Antiaging effects of simvastatin on vascular endothelial cells. Gu, X; Lei, J; Shi, J; Ye, Z; Zheng, X, 2014)	1.44
"Simvastatin treatment resulted in increased mRNA and protein expression of molecules such as TNF, Fas-L, Traf1 and cleaved caspase 8, major mediators of intrinsic apoptosis pathway and reduced protein levels of pro-survival genes Lhx4 and Nme5."	( Simultaneous modulation of the intrinsic and extrinsic pathways by simvastatin in mediating prostate cancer cell apoptosis. Al-Azayzih, A; Al-Husein, B; Goc, A; Kochuparambil, ST; Mohammad, S; Somanath, PR, 2012)	1.34
"Simvastatin treatment stimulated the neurite outgrowth of PCNs after OGD, which was attenuated by LY294002 and enhanced by lithium chloride (LiCl)."	( Simvastatin attenuates axonal injury after experimental traumatic brain injury and promotes neurite outgrowth of primary cortical neurons. Chopp, M; Mahmood, A; Qu, C; Wu, H; Xiong, Y, 2012)	2.54
"Simvastatin treatment increased levels of circulating EPCs and NO."	( Simvastatin increases circulating endothelial progenitor cells and reduces the formation and progression of diabetic retinopathy in rats. Yan, H; Zhang, W, 2012)	2.54
"Simvastatin pretreatment at low (5-20 µM), but not high (50-100 µM) doses markedly reduced apoptosis and increased proliferation and SP-C expression."	( Restoration of alveolar type II cell function contributes to simvastatin-induced attenuation of lung ischemia-reperfusion injury. Fan, X; Feng, D; Jiang, F; Lv, J; Wu, Y; Xu, L; Yin, R; Zhang, Z, 2012)	1.34
"Simvastatin-treated patients had an impaired glucose tolerance and displayed a decreased insulin sensitivity index. "	( Simvastatin effects on skeletal muscle: relation to decreased mitochondrial function and glucose intolerance. Bang, LE; Bundgaard, H; Dela, F; Hansen, CN; Helge, JW; Hey-Mogensen, M; Larsen, S; Nielsen, LB; Stride, N, 2013)	3.28
"Simvastatin treatment increased rat erythrocyte deformability compared with controls (n = 6, P < 0.05)."	( Simvastatin and GGTI-2133, a geranylgeranyl transferase inhibitor, increase erythrocyte deformability but reduce low O(2) tension-induced ATP release. Clapp, KM; Ellsworth, ML; Sprague, RS; Stephenson, AH, 2013)	2.55
"Simvastatin treatment reduces CRP levels, but without affecting the increased risk conferred by higher CRP levels at baseline."	( Inflammatory predictors of mortality in the Scandinavian Simvastatin Survival Study. Bellomo, G; Cianflone, D; Cook, T; Crea, F; Ginnetti, F; Kjekshus, J; Lanza, GA; Maggi, E; Monaco, C; Niccoli, G, 2002)	1.28
"Simvastatin treatment upregulated eNOS expression and reduced the interaction of cytosolic protein with the 3'-untranslated region of eNOS mRNA."	( [Effect of HMG-CoA reductase inhibition on endothelial dysfunction-inducing protein in hypercholesterolemic rabbits]. Arriero, MM; Casado, S; de Andrés, R; Farré, J; García-Colis, E; García-Méndez, A; Gómez, J; Jiménez, AM; Jiménez, P; López-Farré, A; Millás, I, 2002)	1.04
"Simvastatin pretreatment also increased eNOS protein."	( Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage. Laskowitz, DT; Lynch, JR; McGirt, MJ; Parra, A; Pearlstein, RD; Pelligrino, DA; Sheng, H; Warner, DS, 2002)	2.48
"Simvastatin treatment before or after SAH attenuated cerebral vasospasm and neurological deficits in mice. "	( Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage. Laskowitz, DT; Lynch, JR; McGirt, MJ; Parra, A; Pearlstein, RD; Pelligrino, DA; Sheng, H; Warner, DS, 2002)	3.2
"Simvastatin treatment significantly decreased concentrations of vascular cell adhesion molecule and intracellular adhesion molecule after 3 and 6 months of the therapy, respectively."	( Simvastatin and markers of endothelial function in patients undergoing continuous ambulatory peritoneal dialysis. Brzosko, S; Hryszko, T; Malyszko, J; Malyszko, JS; Mysliwiec, M, 2002)	2.48
"Simvastatin-treated animals showed increased expression of endothelial nitric-oxide-synthase (eNOS), and decreased expression of the ox-LDL receptor LOX-1 in renal endothelial cells."	( Lipid-lowering-independent effects of simvastatin on the kidney in experimental hypercholesterolaemia. Chade, AR; Feldstein, A; Lerman, A; Lerman, LO; Napoli, C; Sawamura, T; Wilson, SH, 2003)	1.31
"Simvastatin treatment was associated with cytochrome C release from the mitochondria to the cytosol."	( Bcl-xL overexpression protects from apoptosis induced by HMG-CoA reductase inhibitors in murine tubular cells. Blanco-Colio, LM; Daehn, I; Egido, J; Justo, P; Lorz, C; Ortiz, A, 2003)	1.04
"Simvastatin treatment also increased plasma NO(2)+NO(3) without affecting endothelial function, heart weight index, and blood pressure of control rats."	( Effects of simvastatin on endothelial function after chronic inhibition of nitric oxide synthase by L-NAME. Alvarez de Sotomayor, M; Herrera, MD; Jimenez, L; Marhuenda, E; Pérez-Guerrero, C, 2003)	1.43
"Simvastatin treatment enhanced the expression level of mRNA for osteocalcin and protein for osteocalcin and osteopontin, and increased alkaline phosphatase activity significantly (p<0.05)."	( Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells. Chen, Z; Dang, G; Guo, Z; Jia, H; Liu, Z; Ma, Q; Song, C, 2003)	2.48
"Simvastatin treatment reduced right ventricular hypertrophy and reduced proliferation and increased apoptosis of pathological smooth muscle cells in the neointima and medial walls of pulmonary arteries."	( Simvastatin rescues rats from fatal pulmonary hypertension by inducing apoptosis of neointimal smooth muscle cells. Benson, G; Berry, GJ; Faul, JL; Kao, PN; Nishimura, T; Pearl, RG; Qiu, D; Shi, L; Vaszar, LT; Zhao, G, 2003)	2.48
"Simvastatin treatment decreased the incorporation of acetate in cholesterol (-93.8%) and cholesterol esters (-70.2%), as expected."	( Pharmacological modulation of fatty acid desaturation and of cholesterol biosynthesis in THP-1 cells. Colombo, C; Galli, C; Ghezzi, S; Levati, MG; Mirtini, R; Risé, P, 2003)	1.04
"simvastatin treatment of apoE(-/-) mice caused paradoxical hyperlipidemia and increased intimal hyperplasia."	( Effects of simvastatin on plasma lipoproteins and response to arterial injury in wild-type and apolipoprotein-E-deficient mice. Carrelli, AL; Chereshnev, I; Choudhury, RP; Elmalem, VI; Fallon, JT; Fisher, EA; Reis, ED; Soccio, R; Stern, JD, )	1.24
"Simvastatin treatment did not alter serum total IgE or OVA-specific IgG1 and IgG2a levels."	( A novel anti-inflammatory role of simvastatin in a murine model of allergic asthma. Leung, BP; Liew, FY; McInnes, IB; McKay, A; Thomson, NC, 2004)	1.32
"Simvastatin treatment inhibited the increases in myocardial nitrotyrosine content and in p67-phox and p22-phox expression, and significantly reduced LVH."	( Simvastatin prevents load-induced protein tyrosine nitration in overloaded hearts. Coelho, OR; Franchini, KG; Lagosta, VJ; Moreno, H; Nadruz, W, 2004)	2.49
"Simvastatin treatment had a significant effect of decreasing IL-1beta [668+/-98 vs."	( Simvastatin reduces interleukin-1beta secretion by peripheral blood mononuclear cells in patients with essential hypertension. Li, Q; Liu, L; Xiao, J; Xu, Z; Zhao, S, 2004)	2.49
"Simvastatin treatment at doses of 20 mg-80 mg is well-tolerated in Asian and non-Asian CHD patients."	( Efficacy and safety of simvastatin in Asian and non-Asian coronary heart disease patients: a comparison of the GOALLS and STATT studies. Bilheimer, D; Chung, N; Davies, MJ; Lee, K; Loeys, T; Morales, D; Sangwatanaroj, S; Shah, A; Yin, WH; Zhu, JR, 2004)	1.36
"Simvastatin treatment significantly reduced serum cholesterol, LDL-cholesterol (LDL-C) and apolipoprotein (apo) B levels (p < 0.001). "	( Effect of short term treatment with simvastatin and atorvastatin on lipids and paraoxonase activity in patients with hyperlipoproteinaemia. Balogh, Z; Harangi, M; Illyés, L; Kovács, P; Paragh, G; Seres, I; Törocsik, D, 2004)	2.04
"Simvastatin treatment for 5 years in a placebo-controlled trial, followed by open-label statin therapy, was associated with survival benefit over 10 years of follow-up compared with open-label statin therapy for the past 5 years only. "	( Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S). Cook, TJ; Faergeman, O; Kjekshus, J; Pedersen, TR; Pyörälä, K; Strandberg, TE; Thorgeirsson, G; Wilhelmsen, L, )	1.8
"Simvastatin treatment initiated from 13 weeks after AS operation significantly improved LV function and reduced superoxide levels and cardiomyocyte apoptosis in LV tissues."	( Statins initiated after hypertrophy inhibit oxidative stress and prevent heart failure in rats with aortic stenosis. Chen, MS; Luo, JD; Wang, YZ; Xu, FP; Yi, Q; Zhang, GP; Zhang, HQ, 2004)	1.04
"Simvastatin treatment reduced plasma lipid levels and partially decreased the severity of hyperglycaemia."	( Effects of simvastatin treatment on oxidant/antioxidant state and ultrastructure of streptozotocin-diabetic rat lung. Aktan, F; Can, B; Ceylan, A; Gönül, B; Güven, C; Oz, E; Ozansoy, G, )	1.24
"Simvastatin treatment in older patients was as safe and effective as in younger patients. "	( Primary cardiovascular events and serum lipid levels in elderly Japanese with hypercholesterolemia undergoing 6-year simvastatin treatment: a subanalysis of the Japan lipid intervention trial. Horiuchi, H; Itakura, H; Kita, T; Mabuchi, H; Matsuzaki, M; Matsuzawa, Y; Nakaya, N; Oikawa, S; Saito, Y; Sasaki, J; Shimamoto, K, 2004)	1.98
"Simvastatin treatment stopped the loss of body weight, completely normalized the increase of plasma lipids and partially reduced the hyperglycaemia in diabetic rats."	( Simvastatin treatment restores vasoconstriction and the inhibitory effect of LPC on endothelial relaxation via affecting oxidizing metabolism in diabetic rats. Aktan, F; Ceylan, A; Karasu, C; Ozansoy, G, 2004)	2.49
"Simvastatin treatment in heart transplant recipients decreased myocardium TNF-alpha expression. "	( Simvastatin decreases myocardial tumor necrosis factor alpha content in heart transplant recipients. Becker, KA; Farmer, JA; Koerner, MM; Küçüker, SA; McRee, SC; Noon, GP; Stetson, SJ; Torre-Amione, G; Wallace, CK, 2005)	3.21
"Simvastatin treatment lowered the Rho GTPase activities, whereas the Rho-associated kinase inhibitor Y27632 partially blocked the statin inhibitory effect on nitrite production in the cytokine-treated H9c2 cells."	( Simvastatin attenuates expression of cytokine-inducible nitric-oxide synthase in embryonic cardiac myoblasts. De Caterina, A; De Caterina, R; Di Napoli, P; Felaco, M; Geng, YJ; Grilli, A; Madonna, R; Massaro, M; Tang, D, 2005)	2.49
"Simvastatin treatment produced marked anti-proliferative and pro-aptotic effects in DLD-1."	( Up-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in left-sided human colon cancer. Altomare, DF; Caruso, MG; Guerra, V; Messa, C; Montemurro, S; Notarnicola, M; Pricci, M, )	0.85
"Simvastatin-treated monocytes showed little chemotaxis movement in response to monocyte chemoattractant protein-1 (MCP-1), a specific CCR2 ligand."	( HMG-CoA reductase inhibition reduces monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated monocyte recruitment in vivo. Han, KH; Hong, KH; Kim, JB; Kim, JJ; Ko, J; Pak, YK; Park, SW; Ryu, J, 2005)	1.05
"Simvastatin treatment is not associated with impairment in left ventricular systolic or diastolic function in hypercholesterolaemic subjects after 6 months of treatment."	( Effects of simvastatin on blood lipids, vitamin E, coenzyme Q10 levels and left ventricular function in humans. Colquhoun, DM; Goldsmith, J; Hicks, BJ; Jackson, R; Kostner, KM; Strakosch, C; Walters, M; Young, P, 2005)	1.44
"Simvastatin treatment was not associated with hepatic dysfunction, muscle necrosis, or other adverse events."	( Simvastatin treatment of pulmonary hypertension: an observational case series. Kao, PN, 2005)	2.49
"Simvastatin treatment appears safe in patients with PAH."	( Simvastatin treatment of pulmonary hypertension: an observational case series. Kao, PN, 2005)	3.21
"Simvastatin and ezetimibe treatment reduced LDL cholesterol to a similar extent (15.6% versus 15.4%; P=NS), whereas changes in mevalonate, the product of HMG-CoA-reductase, differed between groups (Deltamevalonate-simvastatin, -1.04+/-0.62 versus Deltamevalonate-ezetimibe, 1.79+/-0.94 ng/mL; P<0.05 between groups)."	( Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans. Bahlmann, F; de Groot, K; Drexler, H; Fauler, G; Fischer, D; Fliser, D; Kirchhoff, N; Landmesser, U; Manes, C; März, W; Mueller, M; Schulz, S; Spiekermann, S, 2005)	2.49
"Simvastatin treatment decreased VLDL+LDL cholesterol, LDL cholesterol, triglycerides and apo B, CETP activity, cholesterol esterification and cholesteryl ester transfer."	( Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment. de Vries, R; Dullaart, RP; Groen, AK; Kerstens, MN; Sluiter, WJ; van Tol, A, 2005)	1.25
"Simvastatin treatment of SLOS fibroblasts with residual DHCR7 enzymatic activity decreased 7DHC levels and increased cholesterol synthesis."	( Residual cholesterol synthesis and simvastatin induction of cholesterol synthesis in Smith-Lemli-Opitz syndrome fibroblasts. Gewandter, JS; Javitt, N; Krakowiak, PA; Porter, FD; Sterner, AL; Wassif, CA; Wright, BS; Yergey, AL, 2005)	1.33
"Simvastatin treatment attenuated myocardial infarct size by 58% in wild-type but not eNOS knockout mice."	( HMG-CoA reductase inhibitors inhibit endothelial exocytosis and decrease myocardial infarct size. Baldwin, WM; Cameron, SJ; Greer, JJ; Lefer, DJ; Lowenstein, CJ; Matsushita, K; Morrell, CN; Talbot-Fox, K; Yamakuchi, M, 2005)	1.05
"In simvastatin-treated isolated hearts, the levels of mRNA expression of SERCA and RyR2 were elevated compared with the control (P<0.05), while the mRNA expression of PLB did not change."	( Effects of simvastatin on cardiac performance and expression of sarcoplasmic reticular calcium regulatory proteins in rat heart. Hu, SJ; Zheng, X, 2005)	1.23
"In simvastatin-treated ischemic animals, the expression of these proteins and caspase-3 activity were significantly lower when compared to that of ischemic animals."	( Simvastatin reduces caspase-3 activation and inflammatory markers induced by hypoxia-ischemia in the newborn rat. Balduini, W; Carloni, S; Cimino, M; De Simoni, MG; Mazzoni, E; Perego, C; Scopa, C, 2006)	2.29
"Simvastatin treatment of 4 yr significantly decreased the elevated levels of serum TC from 234.5 +/- 30.8 to 186.3 +/- 20.5 mg/dL (p < 0.001), low density lipoprotein cholesterol (LDL-C) from 116.7 +/- 22.5 to 82.7 +/- 16.6 mg/dL (p < 0.05) and TG from 200.3 +/- 109.2 to 97.0 +/- 45.2 mg/dL (p < 0.001). "	( Long term efficacy of simvastatin in renal transplant recipients treated with cyclosporine or tacrolimus. Ichimaru, N; Imamura, R; Matsumiya, K; Moriyama, T; Namba, Y; Nonomura, N; Okuyama, A; Shi, Y; Takahara, S; Toki, K, 2005)	2.09
"Simvastatin treatment did not affect apoB levels and only slightly increased the LDL-PAF-AH/LDL-C ratio."	( Modulating effects of cholesterol feeding and simvastatin treatment on platelet-activating factor acetylhydrolase activity and lysophosphatidylcholine concentration. Fan, P; Itabe, H; Matsunaga, A; Miura, S; Saku, K; Shimoji, E; Uehara, Y; Zhang, B, 2006)	1.31
"Simvastatin treatment didn't influence Fb concentration."	( [The comparison of simvastatin and atorvastatin effects on hemostatic parameters in patients with hyperlipidemia type II]. Broncel, M; Chojnowska-Jezierska, J; Kostka, B; Marczyk, I; Michalska, M; Sikora, J, 2005)	1.38
"Simvastatin treatment significantly decreased serum CRP and TNF-a [from 14 +/- 6 to 7 +/- 3 mg/l (p = 0.025) and 30 +/- 5 to 16 +/- 4 pg/ml (p = 0.012), respectively], while quinapril had no significant changes in these 2 measures. "	( Effects of Angiotensin-converting enzyme inhibition and statin treatment on inflammatory markers and endothelial functions in patients with longterm rheumatoid arthritis. Bayindir, P; Bayturan, O; Pirildar, T; Taneli, F; Tikiz, C; Tikiz, H; Tuzun, C; Utuk, O, 2005)	1.77
"The simvastatin group was pretreated with simvastatin 10 mg x kg(-1) x day(-1) for 3 days, whereas the other groups received placebo."	( Pretreatment with simvastatin reduces lung injury related to intestinal ischemia-reperfusion in rats. Aldemir, D; Arslan, G; Candan, S; Ozen, O; Pirat, A; Yücel, M; Zeyneloglu, P, 2006)	1.15
"Simvastatin treatment did not alter serum CETP activity compared to non-treated controls."	( Assessing lipid lowering and plasma cholesteryl ester transfer protein activity of simvastatin following administration to rabbits fed a high fat/cholesterol diet. Lee, SD; Man, D; Risovic, V; Sivak, O; Wasan, KM, 2006)	1.28
"Simvastatin treatment resulted in an increase of GPx activity by 38% (p<0.0001), but did not have a significant effect on TAS."	( Beneficial effect of simvastatin treatment on LDL oxidation and antioxidant protection is more pronounced in combined hyperlipidemia than in hypercholesterolemia. Javorský, M; Molcányiová, A; Stancáková, A; Tkác, I, 2006)	1.37
"Simvastatin treatment significantly reduced circulating conjugated diene level and led to an increase in glutathione peroxidase activity. "	( Beneficial effect of simvastatin treatment on LDL oxidation and antioxidant protection is more pronounced in combined hyperlipidemia than in hypercholesterolemia. Javorský, M; Molcányiová, A; Stancáková, A; Tkác, I, 2006)	2.1
"Simvastatin treatment did significantly (P < 0.05) improve survival (45%) compared with vehicle treatment (25%)."	( Low-dose simvastatin improves survival and ventricular function via eNOS in congestive heart failure. Elrod, JW; Greer, JJ; Jones, SP; Kakkar, AK; Lefer, DJ; Watson, LJ, 2006)	1.47
"Simvastatin treatment did not affect the Th1 response but the results indicated a potential to suppress Th2."	( Effects of simvastatin on human T cells in vivo. Cherfan, P; Jonasson, L; Löfgren, S; Tompa, A; Wikby, A, 2007)	1.45
"Simvastatin treatment resulted in a few discrete changes as regards peripheral T cells. "	( Effects of simvastatin on human T cells in vivo. Cherfan, P; Jonasson, L; Löfgren, S; Tompa, A; Wikby, A, 2007)	2.17
"Simvastatin-treatment commenced 100 days postinfection."	( Simvastatin prolongs survival times in prion infections of the central nervous system. Baier, M; Bamme, T; Gültner, S; Lütjohann, D; Mok, SW; Riemer, C; Thelen, KM, 2006)	2.5
"Simvastatin treatment did not inhibit AgLDL-induced macrophage lipid accumulation, but significantly increased the secretion of IL-1beta and IL-8 from macrophages, whilst inhibiting the secretion of tumor necrosis factor-alpha (TNF-alpha) and having no significant effect on IL-6 secretion."	( Simvastatin stimulates macrophage interleukin-1beta secretion through an isoprenylation-dependent mechanism. Lindholm, MW; Nilsson, J, 2007)	2.5
"Simvastatin treatment modified the plasma expression of FGG chain isoform 1, FGB chain isoforms 1 and 2, vitamin D binding protein isoform 3, apo A-IV, and haptoglobin isoform 2."	( Proteomic study of plasma from moderate hypercholesterolemic patients. Alonso-Orgaz, S; López-Farré, A; Macaya, C; Mateos-Cáceres, PJ; Moreno, L; Pérez-Vizcaíno, F; Rico, L; Sacristán, D; Segura, A; Tamargo, J, 2006)	1.06
"The simvastatin treatment significantly diminished the microglial CCL5 expression induced by IFN-beta alone or by IFN-beta/TNF-alpha combination."	( Suppressive effect of simvastatin on interferon-beta-induced expression of CC chemokine ligand 5 in microglia. Kitani, H; Kuboyama, Y; Kurane, I; Morimoto, K; Nakamichi, K; Saiki, M; Takayama-Ito, M, 2006)	1.13
"Simvastatin treatment not only prevented deterioration of LV function associated with hypercholesterolemia but improved LV function (dP/dtmax +130%; dP/dtmin +144%, P < 0.05)."	( Simvastatin improves left ventricular function after myocardial infarction in hypercholesterolemic rabbits by anti-inflammatory effects. Bauersachs, J; Fraccarollo, D; Hiss, K; Laufs, U; Ruetten, H, 2006)	2.5
"Simvastatin treatment modulates endothelial CD40-sCD40L in both venous and arterial grafts, and therefore may represent a useful tool in the pharmacological prevention of graft failure."	( Simvastatin reduces CD40 expression in an experimental model of early arterialization of saphenous vein graft. Anselmi, A; Chello, M; Covino, E; Di Sciascio, G; Lusini, M; Patti, G; Spadaccio, C, 2006)	3.22
"Simvastatin treatment not only reversed learning and memory deficits in the Tg2576 mice, but also enhanced learning and memory in the nontransgenic mice. "	( Simvastatin enhances learning and memory independent of amyloid load in mice. Cao, D; Fukuchi, K; Kim, H; Lester, R; Li, L, 2006)	3.22
"Simvastatin pre-treatment resulted in a significant reduction in cytotoxicity (lactate dehydrogenase release and caspase 3 activation) following challenge compared with unchallenged neurons."	( Simvastatin protects neurons from cytotoxicity by up-regulating Bcl-2 mRNA and protein. Eckert, GP; Franke, C; Igbavboa, U; Johnson-Anuna, LN; Müller, WE; Wood, WG, 2007)	2.5
"As simvastatin-treated cultures of yeast were passaged, the frequencies of petite cells (respiratory-deficient yeast mutants with deletions in the mitochondrial genome) increased with time and with simvastatin concentration."	( Simvastatin reduces ergosterol levels, inhibits growth and causes loss of mtDNA in Candida glabrata. Macreadie, IG; Westermeyer, C, 2007)	2.3
"Simvastatin treatment with 1 mg/kg for 6 weeks reduced the ischemic injury."	( Simvastatin pretreatment reduces the severity of limb ischemia in an experimental diabetes model. Cakmak, A; Demirpençe, E; Deniz Dinçer, U; Köksoy, A; Köksoy, C; Okcu-Heper, A; Oziş, E; Yazgan, U, 2007)	2.5
"Simvastatin pretreatment reduced limb ischemia-reperfusion injury in diabetic and nondiabetic animals. "	( Simvastatin pretreatment reduces the severity of limb ischemia in an experimental diabetes model. Cakmak, A; Demirpençe, E; Deniz Dinçer, U; Köksoy, A; Köksoy, C; Okcu-Heper, A; Oziş, E; Yazgan, U, 2007)	3.23
"Simvastatin treatment (20 mg.kg(-1).day(-1)) commenced after 2 wk of hypoxia, at which time CHPH was fully established, reduced mean pulmonary artery pressure (19 +/- 0.5 vs."	( Regression of chronic hypoxic pulmonary hypertension by simvastatin. Champion, HC; Girgis, RE; Hassoun, PM; Johns, RA; Li, D; Mozammel, S; Peng, X; Shimoda, L; Tuder, RM, 2007)	1.31
"Simvastatin treatment reduced serum Lp-PLA(2) and lyso-PC content in LDL."	( Lysophosphatidylcholine contents in plasma LDL in patients with type 2 diabetes mellitus: relation with lipoprotein-associated phospholipase A2 and effects of simvastatin treatment. Hattori, H; Higuchi, S; Iida, M; Iwase, M; Ohdo, S; Sasaki, N; Sonoki, K, 2008)	1.26
"Simvastatin but not LT-4 treatment significantly improves EDV of the brachial artery and dyslipidemia in patients with SCH."	( Simvastatin improves endothelial function in patents with subclinical hypothyroidism. Demirtunc, R; Duman, D; Esertas, K; Sahin, S, 2007)	2.5
"Simvastatin treatment also significantly prolonged the survival times of infected mice (193 vs."	( Simvastatin treatment prolongs the survival of scrapie-infected mice. Bate, C; Kempster, S; Williams, A, 2007)	2.5
"The simvastatin treatment resulted in a significant effect in decreasing TF and PAI-1 (69.1 +/- 14.6 ng/l vs."	( Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1 secretion by peripheral blood mononuclear cells in patients with primary nephrotic syndrome. Cui, HM; Ma, CY; Wei, JL, 2007)	2.26
"The simvastatin treatment made the attenuation of the above-mentioned indexes in this animal model (P<0."	( [Effect of simvastatin on rat pulmonary hypertension induced by high pulmonary blood flow and injected monocrotaline]. Dou, H; Li, M; Liu, HM; Tang, ZH; Zhao, L; Zhou, TF, 2007)	1.21
"Simvastatin treatment of the fractured bone showed a significant positive effect on fracture healing. "	( New addition to the statin's effect. Erdemli, E; Kiliçcoglu, SS; Serin-Kilicoglu, S, 2007)	1.78
"Simvastatin treatment of patients reduced the total cholesterol, LDL cholesterol, triglycerides, two of the lipid indices, plasma viscosity and hematocrit."	( Lipid-modifying and pleiotropic effects of gemfibrozil, simvastatin and pravastatin in patients with dyslipidemia. Doncheva, NI; Nikolov, KV; Vassileva, DP, 2006)	1.3
"Simvastatin treatment reduced low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels and improved endothelial-dependent vasodilation in patients after 4 weeks. "	( [The effects after withdrawal of simvastatin on brachial artery endothelial function in patient with coronary heart disease or risk factors]. Chen, H; Li, LJ; Liu, X; Luo, Y; Ren, JY; Wang, RJ; Wu, B, 2007)	2.06
"Simvastatin treatment significantly decreased plasma lipids in all patients (P<0.01). "	( Effect of ScrF I polymorphism in the 2nd intron of the HMGCR gene on lipid-lowering response to simvastatin in Chinese diabetic patients. An, CY; Gao, YY; Liu, XM; Sun, YM; Ying, S, 2007)	2
"The simvastatin-treated groups had significantly higher ratios of PaO(2)/FiO(2) and lower values of respiratory index than the control group. "	( Simvastatin suppresses lung inflammatory response in a rat cardiopulmonary bypass model. Dong, G; Jing, H; Liu, H; Qiang, J; Shao, H; Shen, Y, 2007)	2.34
"Simvastatin treatment significantly increased the number of DiI-acLDL, UEA-1 lectin double-positive EPCs and facilitated its appearance. "	( Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine IL-8 secretion from monocytes. Cho, HJ; Hur, J; Hwang, KK; Kang, HJ; Kim, HS; Oh, BH; Park, KW; Park, YB; Yang, HM; Yoon, CH, 2008)	3.23
"Simvastatin treatment lead to downregulation of many pro-inflammatory genes including several chemokines [e.g."	( Simvastatin has an anti-inflammatory effect on macrophages via upregulation of an atheroprotective transcription factor, Kruppel-like factor 2. Häkkinen, SK; Horrevoets, AJ; Kansanen, E; Levonen, AL; Lumivuori, H; Tuomisto, TT; Turunen, MP; van Thienen, JV; Ylä-Herttuala, S, 2008)	2.51
"Simvastatin treatment significantly increased plasma levels of ApoA-I compared to the other three groups. "	( HMG-CoA reductase inhibitor, simvastatin improves reverse cholesterol transport in type 2 diabetic patients with hyperlipidemia. Guan, JZ; Matsui, J; Matsuki, K; Murakami, H; Suda, T; Tamasawa, N; Tanabe, J; Yamashita, M, 2008)	2.08
"Simvastatin pretreatment for short-term at high dose do not prevent renal function deterioration after administration of contrast medium in patients with baseline renal insufficiency undergoing coronary angiography."	( Prevention of radiocontrast medium-induced nephropathy using short-term high-dose simvastatin in patients with renal insufficiency undergoing coronary angiography (PROMISS) trial--a randomized controlled study. Chae, IH; Cho, YS; Choi, DJ; Choi, YS; Chung, WY; Jo, SH; Kang, HJ; Kim, HS; Kim, YJ; Koo, BK; Oh, BH; Park, JS; Park, YB; Sohn, DW; Youn, TJ, 2008)	2.01
"Simvastatin treatment did not prevent uremia accelerated atherosclerosis in chronic kidney disease apoE(-/-) mice, nor did it retard atherosclerosis progression in control nonchronic kidney disease mice. "	( Effect of simvastatin in apolipoprotein E deficient mice with surgically induced chronic renal failure. Drüeke, TB; Ivanovski, O; Joki, N; Ketteler, M; Lacour, B; Maizel, J; Massy, ZA; Mothu, N; Nguyen-Khoa, T; Nikolov, IG; Szumilak, D; Westenfeld, R, 2008)	2.19
"Simvastatin treatment reduced cell viability in all five melanoma cell lines."	( Simvastatin inhibits growth via apoptosis and the induction of cell cycle arrest in human melanoma cells. Furukawa, H; Mol, W; Oyama, A; Saito, A; Saito, N; Sasaki, S; Sekido, M; Tsutsumida, A; Yamamoto, Y, 2008)	2.51
"Simvastatin treatment has been well tolerated by the patients."	( [Simvastatin in the treatment of familial hypercholesterolemia]. Ceska, R; Kvasilová, M; Procházková, R; Sobra, J, 1995)	1.92
"Simvastatin-treated A10 cells (5 mg/L for 24 hours) showed a normal initial peak response to vasopressin, but the plateau phase of Ca2+ entry was significantly impaired."	( 3-Hydroxy-3-methyl glutaryl coenzyme A reductase inhibition modulates vasopressin-stimulated Ca2+ responses in rat A10 vascular smooth muscle cells. Davies, JE; Ng, LL; Wojcikiewicz, RJ, 1994)	1.01
"Simvastatin treatment was associated with a sustained dose-related reduction in total and LDL cholesterol (-28% and -39% respectively at the end of the study)."	( [Effectiveness and tolerability of simvastatin in subjects with primary hypercholesterolemia. Multicenter study]. Falaschi, F; Finardi, G; Franco, C; Perani, G; Ricciardi, R; Tramarin, R, 1993)	1.28
"Simvastatin treatment decreased total and LDL-cholesterol significantly and was not associated with adverse effects."	( What is the role of lipid lowering therapy in heart-allograft failure? Brandl, U; Meiser, BM; Reichart, B; Seidel, D; Thiery, J; Wenke, K, 1995)	1.01
"Simvastatin treatment increased apo-AI mRNA nearly threefold, whereas apo-AII and apo-AIV decreased by more than 50%."	( Effects of hypolipidemic drugs on the expression of genes involved in high density lipoprotein metabolism in the rat. Auwerx, J; Fruchart, JC; Staels, B; Van Tol, A, 1996)	1.02
"Simvastatin treatment saved an estimated 0.377 undiscounted life years (0.240 life years discounted at 5% per annum)."	( Cost-effectiveness of cholesterol lowering. Results from the Scandinavian Simvastatin Survival Study (4S) Johannesson, M; Jönsson, B; Kjekshus, J; Olsson, AG; Pedersen, TR; Wedel, H, 1996)	1.25
"Simvastatin treatment reduced plasma total cholesterol levels by 18 +/- 2% and low density lipoprotein cholesterol levels by 26 +/- 2% (P < .001 for both), whereas high density lipoprotein cholesterol levels increased slightly (6 +/- 2%, P < .05)."	( No influence of simvastatin treatment on platelet function in vivo in patients with hypercholesterolemia. Angelin, B; Bröijersén, A; Eriksson, M; Hjemdahl, P; Leijd, B, 1997)	1.36
"Simvastatin treatment was also associated with a change in the post-translational modification of the ras protein in smooth muscle cells, probably by inhibition of its farnesylation."	( Inhibition of proliferation of human smooth muscle cells by various HMG-CoA reductase inhibitors; comparison with other human cell types. Cohen, LH; Nègre-Aminou, P; van Erck, M; van Leeuwen, RE; van Thiel, GC; van Vliet, AK, 1997)	1.02
"Simvastatin treatment resulted in a 28% fall in the CSI of bile at the end of therapy (P < 0.01)."	( Dissolution of gallstones with simvastatin, an HMG CoA reductase inhibitor. Allan, RB; Burt, MJ; Chapman, BA; Chisholm, RJ; Ross, AG; Yeo, KH, 1998)	1.31
"Simvastatin treatment reduced plasma campesterol (-24%, P = .017) but did not affect circulating stigmasterol and sitosterol levels."	( Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor on sterol absorption in hypercholesterolemic subjects. Frohlich, JJ; Jones, PJ; Ntanios, FY, 1999)	1.02
"Simvastatin treatment was associated with a shorter LDL residence time (P<.01) and a decrease in LDL glycation (P<.001) with virtually no change in diabetic control (HbA1c, 6.0%+/-3.1% v."	( Association between low-density lipoprotein composition and its metabolism in non-insulin-dependent diabetes mellitus. Collins, P; Deegan, P; Johnson, A; Owens, D; Tomkin, GH, 1999)	1.02
"Simvastatin (10 microm) treatment did not significantly alter either the secretion or intracellular degradation of apoB, relative to control."	( Differential regulation of apolipoprotein B secretion from HepG2 cells by two HMG-CoA reductase inhibitors, atorvastatin and simvastatin. Barrett, PH; Huff, MW; Wilcox, LJ, 1999)	1.23
"Simvastatin treatment caused an increase (72%) in lipoprotein lipase activity without affecting hepatic lipase activity."	( Different effect of simvastatin and atorvastatin on key enzymes involved in VLDL synthesis and catabolism in high fat/cholesterol fed rabbits. Adzet, T; Alegret, M; Díaz, C; Hernández, G; Laguna, JC; Peris, C; Sánchez, RM; Vázquez, M; Verd, JC, 1999)	1.35
"Simvastatin treatment reduced cardiovascular disease-related hospitalizations by 23% in NFG (P = 0.001), 30% in IFG (P = 0.015), and 40% in diabetic subjects (P = 0.007) within trial (median follow-up of 5.4 years)."	( Effect of simvastatin treatment on cardiovascular resource utilization in impaired fasting glucose and diabetes. Findings from the Scandinavian Simvastatin Survival Study. Alexander, CM; Boccuzzi, SJ; Cook, JR; Herman, WH; Kjekshus, J; Musliner, TA; Pedersen, TR; Pyörälä, K, 1999)	1.43
"Simvastatin-treated patients with DM had significantly reduced numbers of major coronary events (relative risk [RR] = 0.58; P = .001) and revascularizations (RR = 0.52; P = .005). "	( Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study. Alexander, CM; Boccuzzi, SJ; Cook, TJ; Haffner, SM; Kjekshus, J; Musliner, TA; Pedersen, TR; Pyörälä, K, )	1.87
"With simvastatin treatment, TC and low-density lipoprotein cholesterol (LDL-C) levels decreased significantly at 1 month in both groups, and these decreased levels were maintained throughout treatment (P < 0.001)."	( Sex-related differences in response of plasma lipids to simvastatin: the Saitama Postmenopausal Lipid Intervention Study. S-POLIS Group. Nakajima, K, 1999)	1
"Simvastatin treatment reduced the mortality risk to 0.33 (95% confidence interval, 0.16 to 0.69) in epsilon4 carriers and to 0.66 (95% confidence interval, 0."	( The apolipoprotein epsilon4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction : a substudy of the Scandinavian simvastatin survival study. Faergeman, O; Gerdes, C; Gerdes, LU; Hansen, PS; Kervinen, K; Kesäniemi, YA; Klausen, IC; Savolainen, M, 2000)	1.25
"Simvastatin treatment had no effect on intracellular cAMP levels."	( Simvastatin improves disturbed endothelial barrier function. Emeis, JJ; Lankelma, J; Nègre-Aminou, P; van Hinsbergh, VW; van Nieuw Amerongen, GP; Vermeer, MA, 2000)	2.47
"Simvastatin treatment reduced the fasting total cholesterol level from 237 +/- 5 to 178 +/- 6 mg/dL (-25%), the LDL cholesterol level from 150 +/- 6 to 87 +/- 5 mg/dL (-40%), and raised high-density lipoprotein-cholesterol (HDL-C) level from 36 +/- 2 to 40 +/- 2 mg/dL (+11%) (all P <.001)."	( Simvastatin treatment on postprandial hypertriglyceridemia in type 2 diabetes mellitus patients with combined hyperlipidemia. Chen, YT; Jeng, CY; Lee, WJ; Lin, SY; Pei, D; Sheu, WH, 2001)	2.47
"Simvastatin treatment depresses blood clotting, which leads to reduced rates of prothrombin activation, factor Va generation, fibrinogen cleavage, factor XIII activation, and an increased rate of factor Va inactivation. "	( Simvastatin depresses blood clotting by inhibiting activation of prothrombin, factor V, and factor XIII and by enhancing factor Va inactivation. Brummel, KE; Mann, KG; Musial, J; Szczeklik, A; Undas, A, 2001)	3.2
"Simvastatin pretreatment inhibited MVEC HILA-DR induction by IFN-gamma, as detected by flow cytometry. "	( Inhibition of interferon-gamma-mediated microvascular endothelial cell major histocompatibility complex class II gene activation by HMG-CoA reductase inhibitors. Bender, JR; Collinge, M; O'Donnell, L; Pardi, R; Sadeghi, MM; Sadigh, K; Tiglio, A, 2001)	1.75
"Simvastatin pretreatment inhibits CIITA and consequent HLA-DR induction by IFN-gamma in MVECs through interference with protein prenylation. "	( Inhibition of interferon-gamma-mediated microvascular endothelial cell major histocompatibility complex class II gene activation by HMG-CoA reductase inhibitors. Bender, JR; Collinge, M; O'Donnell, L; Pardi, R; Sadeghi, MM; Sadigh, K; Tiglio, A, 2001)	1.75
"Simvastatin treatment reduced the atherosclerotic area and total and esterified cholesterol concentrations in the thoracic aorta."	( HMG-CoA reductase inhibitor stabilizes rabbit atheroma by increasing basal NO and decreasing superoxide. Hayashi, T; Iguchi, A; Kano, H; Sumi, D; Thakur, NK; Tsunekawa, T, 2001)	1.03
"The Simvastatin Treats Asians to Target (STATT) study used a titrate-to-goal protocol to evaluate the efficacy and tolerability of simvastatin 20 to 80 mg/d in the treatment of Asian patients with coronary heart disease."	( STATT: a titrate-to-goal study of simvastatin in Asian patients with coronary heart disease. Simvastatin Treats Asians to Target. Cai, NS; Cho, SY; Choi, DH; Chung, N; Fan, WF; Koh, KK; Lee, K; Lee, PY; Lee, S; Lee, SH; Panchavinnin, P; Phankingthongkum, R; Sangwatanaroj, S; Son, JW; Wang, JJ; Yin, WH; Young, MS; Zhu, JR, 2001)	1.15
"Simvastatin treatment significantly decreased serum TC (240+/-29-200+/-22 mg/dl, P<0.001), low-density lipoprotein cholesterol (LDL-C; 114+/-20-99+/-17 mg/dl, P<0.05) and TG levels (217+/-103-130+/-38 mg/dl, P<0.01)."	( Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus. Hatori, M; Ichimaru, N; Inoue, T; Kameoka, H; Kokado, Y; Okuyama, A; Takahara, S; Wang, JD, 2001)	1.3
"Simvastatin 40 mg treatment showed benefit across all patient groups regardless of age, gender or baseline cholesterol value and proved safe and well tolerated."	( The MRC/BHF Heart Protection Study: preliminary results. Armitage, J; Collins, R; Peto, R, )	0.85
"Simvastatin treatment (either 1 or 2 mg/kg body weight for 12 or 20 weeks) increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in SHR rats compared with untreated control SHR rats."	( Simvastatin improves endothelial function in spontaneously hypertensive rats through a superoxide dismutase mediated antioxidant effect. Alvarez de Sotomayor, M; Bravo, L; Carneado, J; Herrera, MD; Jimenez, L; Marhuenda, E; Martin-Sanz, MD; Miranda, M; Pamies, E; Perez-Guerrero, C; Stiefel, P, 2002)	2.48
"Simvastatin treatment also improved acetylcholine (ACh)-induced endothelium-dependent vasorelaxation in isolated aortic rings, which was associated with an increase in NOS-3 expression by approximately 88% in the aorta measured by real time polymerase chain reaction (PCR), P<0.05."	( Anti-atherosclerotic effect of simvastatin depends on the presence of apolipoprotein E. da Cunha, V; Dole, W; Hinchman, J; Huw, LY; Kauser, K; Martin-McNulty, B; Post, J; Sullivan, ME; Vergona, R; Wang, YX, 2002)	1.32
"Simvastatin treatment in 34 male Sprague-Dawley rats accelerated reendothelialization of the balloon-injured arterial segments (reendothelialized area at 2 weeks, 12.3+/-1.8 versus 5.4+/-1.1 mm2, P< 0.01) and resulted in a dose-dependent (0.2 or 1 mg/kg IP) significant reduction in neointimal thickening at 2, 3, and 4 weeks compared with saline-injected controls (n=18). "	( Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Asahara, T; Bahlmann, FH; Isner, JM; Kirchmair, R; Losordo, DW; Murayama, T; Nishimura, H; Rittig, K; Silver, M; Walter, DH, 2002)	1.76
"Simvastatin treatment was associated with reduced cellular proliferation (BrdU), leukocyte accumulation (CD45), and platelet-derived growth factor-induced phosphorylation of the survival factor Akt and increased apoptosis after injury."	( Simvastatin reduces neointimal thickening in low-density lipoprotein receptor-deficient mice after experimental angioplasty without changing plasma lipids. Chen, Z; Detmers, PA; Ehlers, R; Fukutomi, T; Rogers, C; Simon, DI; Wright, SD; Zago, AC, 2002)	2.48
"Simvastatin treatment was initiated with a 10 mg dose for 6 weeks; this was increased to 20 mg and 40 mg at 12 and 18 weeks of follow-up respectively if the total cholesterol level had not decreased to below 5.17 mmol/l."	( Simvastatin in non-insulin-dependent diabetic patients with hypercholesterolaemia. Bonnici, F; Fourie, J; Kotze, TJ; Lourens, W; Omar, MA; Stander, I; Steyn, K; van Lathem, J; Vermaak, WJ; Weich, HF, 1992)	2.45
"With simvastatin treatment, the mean decreases in total cholesterol, low density lipoprotein (LDL) cholesterol, and apolipoprotein B (apo B) were 39%, 46%, and 36%, respectively."	( Treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors in hypercholesterolemia induces changes in the components of the extrinsic coagulation system. Abildgaard, U; Lund, H; Norseth, J; Ose, L; Sandset, PM, )	0.59
"Simvastatin treatment reduced low-density lipoprotein (LDL) cholesterol by 40% after 12 weeks, compared with 33% in the cholestyramine group."	( Simvastatin and cholestyramine in the long-term treatment of hypercholesterolaemia. Nordøy, A; Ytre-Arne, K, 1989)	2.44
"Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo."	( Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis. Abraldes, JG; Alessandria, C; Beuers, U; Campion, D; Caraceni, P; Carol, M; Davis, MM; de Wit, K; Durand, F; Francoz, C; Ginès, P; Jiménez, C; Juanola, A; Kamath, PS; Kazankov, K; Lozano, JJ; Ma, AT; Mookerjee, RP; Morales-Ruiz, M; Napoleone, L; Piano, S; Pose, E; Sidorova, J; Solà, E; Tonon, M; Trebicka, J; Uschner, F; Vargas, V; Watson, H; Zaccherini, G, 2022)	1.41
"Treatment with simvastatin significantly reduced tumour volume and inhibited the Ki67 expression when compared to the control group."	( Simvastatin-loaded liposome nanoparticles treatment for uterine leiomyoma in a patient-derived xenograft mouse model: a pilot study. Afrin, S; Borahay, MA; El Sabeh, M; Kilic, GS; Motamedi, M; Ozpolat, B; Saada, J; Vincent, KL; Yang, J, 2022)	2.5
"Mice treated with simvastatin had significantly fewer generalized seizures during the first three hours without a significant effect on generalized seizures after two weeks."	( Repurposing of cholesterol-lowering agents in status epilepticus: A neuroprotective effect of simvastatin. Baudin, P; Hanin, A; Lecas, S; Navarro, V; Roussel, D, 2023)	1.45
"Treatment with simvastatin 40 mg/day plus rifaximin in patients with decompensated cirrhosis was associated with a significant increase in adverse events requiring treatment withdrawal, particularly rhabdomyolysis, compared with simvastatin 20 mg/day plus rifaximin. "	( Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trial. Abraldes, JG; Alessandria, C; Amin, A; Andrade, RJ; Angeli, P; Bernardi, M; Beuers, U; Campion, D; Caraceni, P; Carol, M; de Wit, K; Domenech, G; Durand, F; Ferrero, J; Ginès, P; Jimenez, C; Kamath, PS; Llopis, M; Mookerjee, RP; Napoleone, L; Piano, S; Pich, J; Pose, E; Roux, O; Solà, E; Torres, F; Trebicka, J; Uschner, FE; Vargas, V; Zaccherini, G, 2020)	1.19
"Pretreatment with simvastatin blunted most of the assessed parameters related to sickness syndrome, including depressive-like behavior and depressed locomotor activity, and attenuated LPS-induced fever. "	( Simvastatin attenuated sickness behavior and fever in a murine model of endotoxemia. Cabral, LDM; Dos Santos, RS; Giusti-Paiva, A; Oliveira, MK; Vilela, FC, 2020)	2.33
"Treatment with simvastatin prevented SNP- and IL-1β-induced nuclear factor kappa B (NF-κB) activity."	( Simvastatin abolishes nitric oxide- and reactive oxygen species-induced cyclooxygenase-2 expression by blocking the nuclear factor κB pathway in rabbit articular chondrocytes. Han, Y; Kim, SJ; Yu, SM, 2020)	2.34
"Treatment with simvastatin resulted in a significant reduction in the frequency of pain (P = 0·0003), oral analgesic use (P = 0·003) and circulating hs-CRP (P = 0·003), soluble (s)E-selectin (P = 0·01), sICAM-1 (P = 0·02), sICAM-3 (P = 0·02) and sVEGF (P = 0·01)."	( Simvastatin reduces vaso-occlusive pain in sickle cell anaemia: a pilot efficacy trial. Hoppe, C; Jacob, E; Kuypers, F; Larkin, S; Styles, L; Vichinsky, E, 2017)	2.24
"Treatment with simvastatin for 24h inhibited histamine release in RBL-2H3 cells in a concentration-dependent manner after stimulation with dinitrophenylated bovine serum albumin (DNP-BSA, as an antigen), ionomycin (a calcium ion [Ca"	( Inhibition of the mevalonate pathway by simvastatin interferes with mast cell degranulation by disrupting the interaction between Rab27a and double C2 alpha proteins. Kiyoi, T; Liu, S; Maeyama, K; Sahid, MNA, 2017)	1.06
"Treatment with simvastatin hindered CRC cell viability and enhanced radiation sensitivity in vitro. "	( Simvastatin enhances radiation sensitivity of colorectal cancer cells. DeVecchio, J; Ferrandon, S; Kalady, MF; Karagkounis, G, 2018)	2.28
"Treatment with simvastatin demonstrated significant decreases in the concentration of protein, TNF-α, IL-1β, IL-6, and lipocalin 2, and the number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid in septic rats."	( Experimental Study of the Protective Effect of Simvastatin on Lung Injury in Rats with Sepsis. Wang, Y; Yang, W; Zhang, R; Zhao, X, 2018)	1.08
"Treatment with simvastatin, a drug known to preserve endothelial function through an unknown mechanism, improved endothelial cell function by upregulating GATA4 expression in HUVECs exposed to hyperglycemia."	( GATA4 protects against hyperglycemia‑induced endothelial dysfunction by regulating NOX4 transcription. Ni, Y; Sun, Z; Wang, Z; Xu, H; Zheng, L, 2018)	0.82
"Pretreatment with simvastatin attenuated isoflurane-elicited changes in NSCs and cognitive function."	( Simvastatin Attenuates Neurogenetic Damage and Improves Neurocongnitive Deficits Induced by Isoflurane in Neonatal Rats. Chen, XL; Lei, S; Li, R; Li, WS; Liu, Y; Lu, HX; Lu, P; Lu, Y; Wang, K; Wang, N; Zhang, H; Zhang, PB; Zheng, J, 2018)	2.25
"Treatment with simvastatin alleviated the sepsis-induced increases in the plasma concentration of intestinal fatty acid binding protein and D-lactic acid, as well as the number of colony-forming units in the bacterial culture of the blood, liver, spleen, and kidney. "	( Effect of Simvastatin on the Intestinal Rho/ROCK Signaling Pathway in Rats With Sepsis. Wang, X; Wang, Y; Yang, W; Zhang, R; Zhao, X, 2018)	1.24
"Treatment with simvastatin down-regulated Mmp-13 and Il-1β and up-regulated Col2a1 and autophagic activity."	( Attenuation of osteoarthritis progression in mice following intra-articular administration of simvastatin-conjugated gelatin hydrogel. Araki, D; Kuroda, R; Matsumoto, T; Matsushita, T; Nagai, K; Nishida, K; Tabata, Y; Takayama, K; Tanaka, T, 2019)	1.07
"Treatment with simvastatin stimulated expression of SOX9 and COL2a and enhanced SOX9 protein in human OA chondrocytes."	( Simvastatin promotes restoration of chondrocyte morphology and phenotype. Askew, EB; Cobb, M; Knudson, CB; Knudson, W; Takahashi, N; Terabe, K, 2019)	2.3
"The treatment with simvastatin (40 mg/die) in HyC (n = 18) significantly reduced total and LDL cholesterol levels, platelet aggregability/activation, ROS production and NO action but did not modify platelet sensitivity to the GLP-1 effects."	( Hypercholesterolemia impairs the Glucagon-like peptide 1 action on platelets: Effects of a lipid-lowering treatment with simvastatin. Barale, C; Cavalot, F; Frascaroli, C; Russo, I, 2019)	1.04
"Treatment with simvastatin-ezetimibe resulted in lower rates of the primary end point than simvastatin-placebo, including 0.9% for patients younger than 65 years (HR, 0.97; 95% CI, 0.90-1.05) and 0.8% for patients 65 to 74 years of age (hazard ratio [HR], 0.96; 95% CI, 0.87-1.06), with the greatest absolute risk reduction of 8.7% for patients 75 years or older (HR, 0.80; 95% CI, 0.70-0.90) (P = .02 for interaction)."	( Effect of Simvastatin-Ezetimibe Compared With Simvastatin Monotherapy After Acute Coronary Syndrome Among Patients 75 Years or Older: A Secondary Analysis of a Randomized Clinical Trial. Bach, RG; Blazing, MA; Bohula, EA; Braunwald, E; Califf, RM; Cannon, CP; Giugliano, RP; Lokhnygina, Y; White, JA, 2019)	1.26
"Treatment with simvastatin (P<0.001) and simvastatin plus ezetimibe (P<0.001) significantly decreased GLUT4 protein expression in the adipocytes compared to control conditions. "	( Coenzyme Q10 ameliorates the reduction in GLUT4 transporter expression induced by simvastatin in 3T3-L1 adipocytes. Ganesan, S; Ito, MK, 2013)	0.97
"Treatment with simvastatin significantly reduced the MPO activity in the continuously ventilated lung but had no effect on lung edema after OLV."	( Simvastatin attenuates neutrophil recruitment in one-lung ventilation model in rats. Antunes, E; Braga, Ade F; Camargo, EA; Landucci, EC; Leite, CF; Marangoni, FA; Mussi, RK; Toro, IF, 2013)	2.17
"Treatment with simvastatin significantly reduced mitochondrial content as well as cell viability which were both rescued by simultaneous treatment with ubiquinol."	( Ubiquinol rescues simvastatin-suppression of mitochondrial content, function and metabolism: implications for statin-induced rhabdomyolysis. Bisoffi, M; Conn, CA; Garcia-Smith, R; Trujillo, KA; Vaughan, RA, 2013)	1.06
"Treatment with simvastatin significantly reduced MMP-9 levels and the MMP-9/TIMP-1 ratio (P < .05) when compared to the placebo group (P > .05)."	( Simvastatin therapy decreases MMP-9 levels in obese women. Andrade, VL; do Valle, IB; Sandrim, VC, 2013)	2.17
"Pretreatment with simvastatin and mevastatin suppressed this release to basal level, while pravastatin had no effect."	( Anti-atherogenic effects of statins: Impact on angiopoietin-2 release from endothelial cells. Baumgarten, G; Frede, S; Hilbert, T; Hoeft, A; Klaschik, S; Knuefermann, P; Poth, J, 2013)	0.71
"Treatment with simvastatin resulted in inhibition of the MAPK pathway and exhibited differential effects on the AKT/mTOR pathway in the ECC-1 and Ishikawa cells."	( Simvastatin, an HMG-CoA reductase inhibitor, exhibits anti-metastatic and anti-tumorigenic effects in endometrial cancer. Bae-Jump, VL; Gehrig, PA; Gilliam, TP; Han, X; Kim, K; Schointuch, MN; Stine, JE; Zhou, C, 2014)	2.18
"Treatment with simvastatin plus ezetimibe strongly reduced levels of serum oxysterols and attenuated CKD-dependent atherosclerosis, vascular cell death, vascular calcification, and cardiac dysfunction."	( Endoplasmic reticulum stress effector CCAAT/enhancer-binding protein homologous protein (CHOP) regulates chronic kidney disease-induced vascular calcification. Cavasin, MA; Chonchol, M; Demos-Davies, KM; Jablonski, K; Keenan, AL; Kendrick, J; Levi, M; Masuda, M; Masuda, R; McKinsey, TA; Miyazaki, M; Miyazaki-Anzai, S; Saunders, SJ, 2014)	0.74
"The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality."	( [Antioxidant protection of statins in acute kidney injury induced by sepsis]. Fonseca, CD; Santos, Fdo N; Vasco, CF; Vattimo, Mde F; Watanabe, M, 2014)	0.73
"Treatment with simvastatin restored sensitivity of BFTC-905-DOXO-II to doxorubicin to that of the parental cell line."	( Establishment and characterization of a bladder cancer cell line with enhanced doxorubicin resistance by mevalonate pathway activation. Greife, A; Hatina, J; Schulz, WA; Scott, SD; Steinhoff, C; Tukova, J, 2015)	0.76
"Treatment with simvastatin resulted in a significant decrease not only in mPAP and RVHI but also in a 5-HTT level in serum and BALF (P < 0.01 or 0.05) with a good correlation between the 5-HTT level and mPAP or RVHI (r = 0.693 and 0.479; 0.675 and 0.508)."	( Simvastatin mitigates functional and structural impairment of lung and right ventricle in a rat model of cigarette smoke-induced COPD. Jiang, X; Li, Z; Sun, W; Wang, L; Wang, Y; Zhang, L, 2014)	2.18
"Pre-treatment with simvastatin (S-L) reduced IL-6 (P = 0.02), TNF-α (P = 0.02), and MMP-9 (P = 0.01); post-treatment (L-S) reduced IL-1β (P = 0.02) and TNF-α (P = 0.04), while simultaneous treatment (L+S) did not reduce any of the cytokines tested."	( The Effect of Simvastatin on Infection-Induced Inflammatory Response of Human Fetal Membranes. Basraon, SK; Costantine, MM; Menon, R; Saade, G, 2015)	1.1
"Treatment with simvastatin seems to be well tolerated with superior antidepressant effects compared to atorvastatin in post-CABG patients. "	( Simvastatin versus atorvastatin for improving mild to moderate depression in post-coronary artery bypass graft patients: A double-blind, placebo-controlled, randomized trial. Abbasi, SH; Akhondzadeh, S; Beglar, AA; Forghani, S; Mohammadinejad, P; Salehiomran, A; Shahmansouri, N; Zeinoddini, A, 2015)	2.21
"Pretreatment with simvastatin prevented alendronate-induced macroscopic gastric damage and reduced the levels of MDA and GSH, TNF-α and IL-1β, MPO activity, and mucus levels, in the stomach."	( Protective Effects of Simvastatin Against Alendronate-Induced Gastric Mucosal Injury in Rats. Araújo, TS; Carvalho, NS; Costa, DS; Medeiros, JV; Nicolau, LA; Silva, MM; Silva, RO; Soares, PM; Sousa, NA; Souza, LK, 2016)	1.08
"Treatment with simvastatin in an orthotopic mouse model reduced ovarian tumor growth, coincident with decreased Ki-67, HMGCR, phosphorylated-Akt and phosphorylated-p42/44 protein expression."	( The HMG-CoA reductase inhibitor, simvastatin, exhibits anti-metastatic and anti-tumorigenic effects in ovarian cancer. Bae-Jump, VL; Gehrig, PA; Gilliam, TP; Guo, H; Han, X; Schointuch, MN; Sheng, X; Stine, JE; Zhou, C, 2016)	1.06
"Treatment with simvastatin could partly reverse the MPTP-induced changes in ZO-1 expression and reduce MMP-9 protein and activity."	( Protective effect of simvastatin on impaired intestine tight junction protein ZO-1 in a mouse model of Parkinson's disease. Fang, X; Xu, RS, 2015)	1.08
"Pretreatment by simvastatin and fenofibrate prevented CPB-induced endothelial dysfunction."	( Lipid-lowering drugs prevent neurovascular and cognitive consequences of cardiopulmonary bypass. Amr, G; Azzaoui, R; Bordet, R; Delassus, L; Fossaert, E; Modine, T; Ouk, T; Tailleux, A, 2016)	0.77
"Treatment with simvastatin significantly attenuated LPS-stimulated production of IL-1β, IL-6, VCAM-1 and ICAM-1 (P < 0.05)."	( Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells. Choi, CH; Hwang, YC; Jung, JY; Kim, WJ; Koh, JT; Lee, BN; Lee, KJ; Min, KS; Nör, JE; Woo, SM, 2017)	2.24
"Treatment with simvastatin significantly decreased airway inflammation and inflammatory cell infiltration."	( Evaluation of Simvastatin and Bone Marrow-Derived Mesenchymal Stem Cell Combination Therapy on Airway Remodeling in a Mouse Asthma Model. Boskabady, MH; Golchoobian, R; Jahromi, GP; Kashani, IR; Mohammadian, M; Nejad, AK; Omidi, A; Sadeghipour, HR, 2016)	1.13
"Treatment with simvastatin to inhibit HMG CoA reductase, the rate limiting enzyme of this pathway, induced apoptosis in the 28-2 cell line."	( Ovarian tumour growth is characterized by mevalonate pathway gene signature in an orthotopic, syngeneic model of epithelial ovarian cancer. DiMattia, G; Greenaway, JB; Hardy, D; Osz, K; Petrik, J; Revay, T; Shepherd, T; Virtanen, C, 2016)	0.77
"Treatment with simvastatin of 12 weeks may increase the serum level adiponectin in patients at risk for cardiovascular diseases, but not for the short term treatment of ≤ 8 weeks."	( Effects of simvastatin on serum adiponectin: a meta-analysis of randomized controlled trials. Bi, M; Chen, W; Huang, Z; Xu, X; Zhao, N, 2017)	1.2
"Treatment with simvastatin results in rapid and significant improvement of measures of endothelial activation, suggesting a potential role of statins in the treatment of peripheral vascular disease in SSc. "	( Simvastatin reduces endothelial activation and damage but is partially ineffective in inducing endothelial repair in systemic sclerosis. Comina, DP; Cortelezzi, A; Cortiana, M; Del Papa, N; Lucchi, T; Maglione, W; Silvestris, I; Vitali, C, 2008)	2.14
"Pretreatment with simvastatin and manumycin A clearly affected the activation of Ras promoted by high glucose."	( Simvastatin alleviates diabetes-induced VEGF-mediated nephropathy via the modulation of Ras signaling pathway. Ho, C; Hsu, YC; Lin, CL; Tseng, CC; Wang, FS; Wang, JY, 2008)	2.11
"Pretreatment with simvastatin protected against alpha-toxin-induced sepsis associated with reduced p53, TNF-alpha, apoptosis, and necrosis."	( Apoptosis contributes to septic cardiomyopathy and is improved by simvastatin therapy. Buerke, M; Buerke, U; Carter, JM; Grandel, U; Grimminger, F; Mueller-Werdan, U; Russ, M; Schlitt, A; Schmidt, H; Seeger, W; Sibelius, U; Werdan, K, 2008)	0.91
"Treatment with simvastatin did not influence CoQ10 levels and redox status."	( Plasma and thrombocyte levels of coenzyme Q10 in children with Smith-Lemli-Opitz syndrome (SLOS) and the influence of HMG-CoA reductase inhibitors. Andler, W; Haas, D; Hoffmann, GF; Menke, T; Niklowitz, P, 2008)	0.69
"Treatment with simvastatin dose-dependently decreased CSF leukocyte counts, a marker for CNS inflammation."	( Simvastatin attenuates leukocyte recruitment in experimental bacterial meningitis. Angele, B; Koedel, U; Pfister, HW; Winkler, F, 2009)	2.14
"Pretreatment with simvastatin (10 mg/kg, orally, for 2 weeks) caused significant reduction in gastric mucosal lesions and lipid peroxides associated with a significant increase in gastric juice mucin concentration."	( Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: role of nitric oxide and prostaglandins. Amin, RS; Hassan, MK; Heeba, GH, 2009)	0.97
"Pretreatment with simvastatin reduced LPS-induced BALF neutrophilia, myeloperoxidase, tumor necrosis factor-alpha, matrix metalloproteinases 7, 8, and 9, and C-reactive protein (CRP) as well as plasma CRP (all P < 0.05 vs. "	( Simvastatin decreases lipopolysaccharide-induced pulmonary inflammation in healthy volunteers. Backman, JT; Brown, V; Craig, TR; Elborn, JS; Matthay, MA; McAuley, DF; McKeown, ST; O'Kane, CM; Shyamsundar, M; Taggart, CC; Thickett, DR, 2009)	2.13
"Pretreatment with simvastatin inhibited the induction of CTGF and collagen-Ialpha2, PAI-1 activation, F-actin bundling and FPCL contraction."	( Simvastatin impairs smad-3 phosphorylation and modulates transforming growth factor beta1-mediated activation of intestinal fibroblasts. Burke, JP; Coffey, JC; Docherty, NG; Murphy, M; O'Connell, PR; Watson, RW, 2009)	2.12
"Treatment with simvastatin alone led to a mean (95% CI) % reduction from baseline in low-density lipoprotein-cholesterol (LDL-C) of -36% (-27, -46) compared with a reduction of -54% (-44, -63) for anacetrapib co-administered with simvastatin."	( Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Bieberdorf, FA; Chodakewitz, J; Garg, A; Jin, B; Keshavarz, SS; Krishna, R; Wagner, JA, 2009)	0.92
"Treatment with simvastatin substantially decreased the prevalence of atherosclerotic changes, but otherwise did not change individual serum lipids including LDL cholesterol."	( Antiatherogenic effect of simvastatin is not due to decrease of LDL cholesterol in ovariectomized golden Syrian hamster. Bobková, D; Havlíčková, J; Kovář, J; Pitha, J; Poledne, R, 2010)	1
"Treatment with simvastatin (20 mg/d) or fenofibrate (267 mg/d) was initiated in all DM patients due to fasting hyperlipemia, and in the AH group."	( Postprandial lipemia in diabetic men during hypolipemic therapy. Kreczyńska, B; Poreba, R; Skoczyńska, A, )	0.47
"Treatment with simvastatin significantly lowered peripheral blood TC, LDL-C, kidney/body weight ratio, urinary excretion rates of ALB, RBP, and MMP-9 as well as the expression of renal MMP-9 mRNA (p<0.01); however, there was no evident effect on the change of blood glucose and HbA1c levels between group D and group S."	( Simvastatin protects diabetic rats against kidney injury through the suppression of renal matrix metalloproteinase-9 expression. Chen, K; Chen, Y; Li, XC; Wang, YX; Yang, GW; Yao, XM; Ye, SD; Zai, Z, 2010)	2.14
"Treatment with simvastatin resulted in a significant increase in bowel and mucosal weight in ileum, villus height and crypt depth in jejunum and ileum compared to IR animals. "	( Effect of simvastatin on intestinal recovery following gut ischemia-reperfusion injury in a rat. Bashenko, Y; Chemodanov, E; Coran, AG; Mogilner, J; Shaoul, R; Slijper, N; Sukhotnik, I, 2010)	1.12
"Treatment with simvastatin prevents gut mucosal damage and inhibits programmed cell death following intestinal IR in a rat."	( Effect of simvastatin on intestinal recovery following gut ischemia-reperfusion injury in a rat. Bashenko, Y; Chemodanov, E; Coran, AG; Mogilner, J; Shaoul, R; Slijper, N; Sukhotnik, I, 2010)	1.12
"Treatment with simvastatin (vasilip) at a daily dose of 20 mg combined with conventional cardiac therapy was given for 3 months to 132 patients with coronary heart disease and postinfarction cardiosclerosis with dyslipidemia. "	( [Correction of antioxidative state during statin therapy of coronary heart disease with dyslipidemia]. Artamoshina, NE; Baĭder, LM; Belaia, OL; Kuropteva, ZV; Radzevich, AE, 2009)	0.71
"Treatment with simvastatin or β-cyclodextrin, two cholesterol-lowering drugs, reduced the content of ordered domains at the cell surface, which in turn, protected cells against NMDA-mediated excitotoxicity."	( Altered cholesterol homeostasis contributes to enhanced excitotoxicity in Huntington's disease. Alberch, J; Canals, JM; del Toro, D; Humbert, S; Pol, A; Saudou, F; Xifró, X, 2010)	0.7
"Treatment with simvastatin appears to be safe and may be associated with an improvement in organ dysfunction in ALI. "	( A randomized clinical trial of hydroxymethylglutaryl- coenzyme a reductase inhibition for acute lung injury (The HARP Study). Craig, TR; Duffy, MJ; Elborn, JS; McAuley, DF; McDowell, C; O'Kane, CM; Shyamsundar, M, 2011)	0.72
"Treatment with simvastatin was associated with significant reductions in serum anti-HSP60, 65, and 70 titers in the dyslipidemic patients (10%, 14%, and 15% decrease, respectively) (p<0.001). "	( Simvastatin treatment reduces heat shock protein 60, 65, and 70 antibody titers in dyslipidemic patients: A randomized, double-blind, placebo-controlled, cross-over trial. Akhlaghi, S; Amini, M; Azarpazhooh, MR; Bidmeshgi, S; Daloee, MH; Ferns, GA; Ghayour-Mobarhan, M; Momenzadeh, A; Moohebati, M; Parizadeh, SM; Paydar, R; Rahsepar, AA; Sahebkar, A; Tavallaie, S, 2011)	2.16
"Treatment with simvastatin attenuated goblet cell hyperplasia, arginase-1 protein expression, and total arginase enzyme activity, but it did not alter airway hydroxyproline content or transforming growth factor-β1."	( Simvastatin inhibits goblet cell hyperplasia and lung arginase in a mouse model of allergic asthma: a novel treatment for airway remodeling? Bratt, JM; Kenyon, NJ; Last, JA; Rabowsky, M; Zeki, AA, 2010)	2.14
"Treatment with simvastatin significantly inhibited the fibrosis around coronary arteries in Ang II/salt-loading AM(+/-) mice."	( Protective effects of statin on cardiac fibrosis and apoptosis in adrenomedullin-knockout mice treated with angiotensin II and high salt loading. Fukuda, N; Jumabay, M; Matsumoto, K; Matsumoto, T; Saito, K; Shimosawa, T; Soma, M; Ueno, T; Yamamoto, C, 2011)	0.71
"Treatment with simvastatin triggered the loss of lipid raft localised Rac1 and reduction of Rac1 activity in Mz-ChA-1 cells."	( Simvastatin stimulates apoptosis in cholangiocarcinoma by inhibition of Rac1 activity. Dostal, DE; Glaser, SS; Guerrier, M; Meng, F; Miller, T; Munshi, MK; Priester, S; Wise, CE; Yang, F, 2011)	2.15
"Pretreatment with simvastatin decreased the severity of ALI in oleic acid and endotoxin ALI models, by decreasing inflammation and oxidative stress."	( Long-term simvastatin attenuates lung injury and oxidative stress in murine acute lung injury models induced by oleic Acid and endotoxin. Altintas, ND; Atilla, P; Iskit, AB; Topeli, A, 2011)	1.11
"Treatment with simvastatin or atorvastatin resulted in 40 per cent and 80 per cent of patients, respectively, reaching the 2.5 mmol/l goal and 12 per cent and 52 per cent, respectively, reaching the 2.0 mmol/l goal, after 1 year (all p < 0.001 between groups)."	( LDL cholesterol goals and cardiovascular risk during statin treatment: the IDEAL study. Faergeman, O; Fayyad, R; Holme, I; Kastelein, JJ; Larsen, ML; Lindahl, C; Olsson, AG; Pedersen, TR; Tikkanen, MJ, 2011)	0.71
"Pretreatment of simvastatin significantly decreased eNOS immunoreactivity in the germ cell of the tubules in the rat testes."	( Simvastatin induces the expression of hemeoxygenase-1 against ischemia-reperfusion injury on the testes in rats. Chen, CF; Chen, SC; Chuang, SJ; Hour, TC; Liu, YH; Tu, YP, 2011)	2.15
"Pre-treatment with simvastatin did not alter IS-induced changes."	( Lack of modulatory effect of simvastatin on indoxyl sulfate-induced activation of cultured endothelial cells. Cheng, CI; Chi, PJ; Chiou, TT; Kuo, CC; Lee, CT; Lee, WC; Lee, YT; Ng, HY; Wu, CH, 2012)	0.99
"Pretreatment with simvastatin, 10 mg/kg, given orally for 5 days before the ischemia-reperfusion insult, improved the neurologic outcome and preserved more normal motor neurons compared with the control group in a rat model of spinal cord ischemia-reperfusion."	( Effect of pretreatment with simvastatin on spinal cord ischemia-reperfusion injury in rats. Han, JI; Han, S; Hwang, J, 2013)	1.02
"Treatment with simvastatin and ezetimibe was not associated with less new-onset AF (odds ratio 0.89 [95% CI 0.57-1.97], P = .717)."	( Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Bang, CN; Boman, K; Egstrup, K; Gohlke-Baerwolf, C; Greve, AM; Køber, L; Nienaber, CA; Ray, S; Rossebø, AB; Wachtell, K, 2012)	0.93
"Treatment with simvastatin resulted in a decrease in 4-HNE and TNF-α concentration (median 4.18 μg/mg protein vs. "	( Simvastatin decreases free radicals formation in the human abdominal aortic aneurysm wall via NF-κB. Demyanets, S; Domenig, C; Goraca, A; Huk, I; Klinger, M; Mittlboeck, M; Nanobachvili, J; Neumayer, C; Piechota-Polanczyk, A; Wojta, J, 2012)	2.17
"Treatment with simvastatin 40 mg was an inclusion criterion."	( [Lipid therapy in daily routine]. Bestehorn, K; Gitt, AK; Jannowitz, C; Karmann, B; Pittrow, D; Schaefer, JR; Sonntag, F; Weizel, A, 2012)	0.72
"Treatment with simvastatin markedly inhibited MMP-2, MMP-3, and MMP-9 levels in lung and prevented alveolar destruction."	( Prevention of alveolar destruction and airspace enlargement in a mouse model of pulmonary lymphangioleiomyomatosis (LAM). Albelda, SM; Colby, TV; Ducka, B; Fehrenbach, M; Goncharov, DA; Goncharova, EA; Haczku, A; Hino, O; Khavin, I; Krymskaya, VP; Merrilees, MJ, 2012)	0.72
"Pretreatment with simvastatin decreased the shunt-induced RVSP, MA/TA and F% in pulmonary arteries."	( Simvastatin attenuates pulmonary vascular remodelling by down-regulating matrix metalloproteinase-1 and -9 expression in a carotid artery-jugular vein shunt pulmonary hypertension model in rats. Chen, G; Liang, M; Ma, X; Tang, B; Wang, Z; Wu, Z; Xiong, M; Yao, J, 2012)	2.15
"Pretreatment with simvastatin prior to and continued throughout smoke exposure reduced the total influx of leukocytes, neutrophils and macrophages into the lung and airways."	( Simvastatin inhibits smoke-induced airway epithelial injury: implications for COPD therapy. Bratt, JM; Davis, BB; Filosto, S; Goldkorn, T; Kenyon, NJ; Pinkerton, KE; Schelegle, ES; Walby, WF; Wang, L; Zeki, AA, 2013)	2.16
"Treatment with simvastatin improved alveolar bone loss within all of the parameters studied, thus demonstrating anti-inflammatory and antioxidant activity. "	( Protective mechanisms of simvastatin in experimental periodontal disease. Brito, GA; Dalcico, R; de Menezes, AM; Deocleciano, OB; Oriá, RB; Ribeiro, RA; Vale, ML, 2013)	1.05
"Treatment with simvastatin from 3 days before LPS prevented the increase in baseline perfusion pressure and totally normalized the vasodilating response of the liver vasculature to acetylcholine and reduced liver inflammation."	( Effects of simvastatin administration on rodents with lipopolysaccharide-induced liver microvascular dysfunction. Abraldes, JG; Bosch, J; García-Pagán, JC; Gracia-Sancho, J; Hide, D; La Mura, V; Meireles, CZ; Miquel, R; Pasarín, M; Rodríguez-Vilarrupla, A, 2013)	1.12
"Treatment with simvastatin/ezetimibe 10/10 mg induced no difference in endothelial function in the fasting and postprandial state compared to simvastatin 80 mg while attaining similar LDL-c levels in obese patients with metabolic syndrome."	( High-dose statin monotherapy versus low-dose statin/ezetimibe combination on fasting and postprandial lipids and endothelial function in obese patients with the metabolic syndrome: The PANACEA study. Basart, DC; Coll, B; Deanfield, JE; Imholz, BP; Kastelein, JJ; Spiering, W; Visseren, FL; Westerink, J, 2013)	0.74
"The treatment of simvastatin down-regulated the formation of microclots in the SAH model and the number of microthrombi decreased significantly in the SAH + simvastatin group as compared with the SAH or SAH + vehicle groups (P < 0.01)."	( [Impact of simvastatin on microthrombosis in cortical after subarachnoid hemorrhage in rats and its mechanism]. Chen, G; Wang, Z; Zhu, Y, 2012)	1.1
"Pretreatment with simvastatin significantly inhibited exotoxin-induced leukocyte rolling from 71+/-10 to 14+/-4.7 cells/min (P<0.01) and adherence from 14+/-3.5 to 0.4+/-0.2 cells (P<0.01)."	( Simvastatin inhibits inflammatory properties of Staphylococcus aureus alpha-toxin. Buerke, M; Buerke, U; Dahm, M; Darius, H; Grandel, U; Grimminger, F; Makowski, J; Meyer, J; Oelert, H; Pruefer, D; Schnell, M; Seeger, W; Sibelius, U, 2002)	2.08
"Treatment with simvastatin 20, 40, and 80 mg led to significant reductions in CRP plasma levels versus placebo (p <0.05)."	( Effects of simvastatin on C-reactive protein in mixed hyperlipidemic and hypertriglyceridemic patients. Bays, HE; Maccubbin, DL; Mercuri, M; Mitchel, YB; Shah, AK; Stein, EA, 2002)	1.04
"Upon treatment, the simvastatin FH group showed significant absolute reductions of total cholesterol (TC) (-2.16 +/- 1.04 mmol/l, 30.1%) and low-density lipoprotein cholesterol (LDL-C) (-2.13 +/- 0.99 mmol/l, 39.8%)."	( Early statin therapy restores endothelial function in children with familial hypercholesterolemia. Bakker, HD; de Jongh, S; Kastelein, JJ; Lilien, MR; op't Roodt, J; Stroes, ES, 2002)	0.63
"Treatment with simvastatin (20 mg/kg) after MCAO prevented the increase in brain infarct volume occurring at 24 hours and induced a 46.6% reduction after 48 hours."	( Treatment with statins after induction of focal ischemia in rats reduces the extent of brain damage. Asdente, M; Balduini, W; Calvio, AM; Cimino, M; Guerrini, U; Lodetti, B; Paoletti, R; Sironi, L; Tremoli, E, 2003)	0.66
"Pretreatment with simvastatin reduces neutrophil adhesion to the venous endothelium in patients undergoing coronary surgery, irrespective of its efficacy at lowering cholesterol concentration."	( Simvastatin attenuates leucocyte-endothelial interactions after coronary revascularisation with cardiopulmonary bypass. Chello, M; Covino, E; D'Ambrosio, A; Di Sciascio, G; Mastroroberto, P; Morichetti, MC; Patti, G, 2003)	2.1
"Treatment with simvastatin was associated with significantly greater reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C), while the decrease in triglycerides was significantly greater in patients receiving fenofibrate."	( Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles. Chen, MF; Chen, WJ; Cheng, CC; Lee, YT; Lin, JW; Wang, TD, 2003)	0.95
"Pretreatment with simvastatin, fluvastatin or pravastatin potentiated the TNF-alpha and LPS-induced expression of E-selectin and VCAM-1, and mevalonate reversed the potentiating effect of these statins. "	( Effects of statins on adhesion molecule expression in endothelial cells. de Moerloose, P; Dimitrova, Y; Dunoyer-Geindre, S; Kruithof, EK; Mach, F; Reber, G, 2003)	0.65
"Treatment with simvastatin markedly reduced retinal permeability (P = 0.014)."	( Simvastatin inhibits leukocyte accumulation and vascular permeability in the retinas of rats with streptozotocin-induced diabetes. Hirose, F; Honda, Y; Katsuta, H; Kiryu, J; Miyahara, S; Miyamoto, K; Nishijima, K; Tamura, H; Tsujikawa, A; Yamashiro, K, 2004)	2.11
"Treatment with simvastatin markedly reduced serum triacylglycerol and cholesterol, and partially controlled hyperglycemia in diabetic animals."	( Effects of simvastatin treatment on oxidant/antioxidant state and ultrastructure of diabetic rat myocardium. Aktan, F; Can, B; Ceylan, A; Güven, C; Karasu, C; Ozansoy, G, 2003)	1.05
"Mice treated with simvastatin and rendered septic by cecal ligation and perforation (CLP) show a mean survival time close to 4 times the value found in untreated mice. "	( HMG-CoA reductase inhibitor simvastatin profoundly improves survival in a murine model of sepsis. Hanrath, P; Janssens, U; Liehn, EA; Lütticken, R; Merx, MW; Schrader, J; Weber, C, 2004)	0.95
"Pretreatment with simvastatin (30 or 60 mg/kg) markedly attenuated inhibition of vasodilator responses to ACh, the increased level of TNF-alpha and the decreased level of NO by LDL, but no effect on serum concentration of endogenous ADMA."	( Effect of simvastatin on endothelium-dependent vaso-relaxation and endogenous nitric oxide synthase inhibitor. Deng, HW; Jiang, DJ; Jiang, JL; Li, NS; Li, YJ; Tang, YH, 2004)	1.05
"Treatment with simvastatin did not alter ex vivo T-lymphocyte proliferation."	( Simvastatin inhibits lymphocyte function in normal subjects and patients with cardiovascular disease. Cameron, AJ; Hillyard, DZ; Jardine, AG; MacIntyre, A; McDonald, KJ; Panarelli, M; Shiels, PG; Thomson, J, 2004)	2.11
"Treatment with simvastatin might downregulate enhanced CD40L-CD40 interactions in CAPD patients."	( Increased soluble CD40L levels are reduced by long-term simvastatin treatment in peritoneally dialyzed patients. Hryszko, T; Malyszko, J; Malyszko, JS; Mysliwiec, M, 2004)	0.91
"Pretreatment of simvastatin suppressed the hydrogen peroxide-induced apoptosis of cultured cardiomyocytes from neonatal rats."	( Statins initiated after hypertrophy inhibit oxidative stress and prevent heart failure in rats with aortic stenosis. Chen, MS; Luo, JD; Wang, YZ; Xu, FP; Yi, Q; Zhang, GP; Zhang, HQ, 2004)	0.66
"Treatment with simvastatin significantly (p<0.05) reduced total cholesterol, total triglycerides and low-density lipoprotein cholesterol (LDL-C)."	( The effect of simvastatin therapy on hemorheological profile in coronary heart desease (CHD) patients. Muravyov, AV; Petrochenko, A; Surovaya, L; Yakusevich, VV, 2004)	1.02
"Pretreatment with simvastatin significantly reduces the increase of ICAM-1 and ELAM-1 after coronary artery bypass surgery, by a mechanism that seems not related to its efficacy in lowering cholesterol levels."	( Simvastatin blunts the increase of circulating adhesion molecules after coronary artery bypass surgery with cardiopulmonary bypass. Agrò, F; Carassiti, M; Chello, M; Colonna, D; Covino, E; Mastroroberto, P; Pugliese, G, 2004)	2.1
"Treatment with simvastatin resulted in dose-dependent reductions of fasting LDL-cholesterol, without changing cholesterol levels in the VLDL-1, VLDL-2 and IDL fractions."	( Effects of increasing doses of simvastatin on fasting lipoprotein subfractions, and the effect of high-dose simvastatin on postprandial chylomicron remnant clearance in normotriglyceridemic patients with premature coronary sclerosis. Buirma, R; Castro Cabezas, M; De Jaegere, PP; Halkes, CJ; Plokker, HW; van der Helm, YJ; van Tol, A; van Wijk, JP, 2005)	0.95
"Treatment with simvastatin also induced a significant increase in apoA-I production rate compared to atorvastatin (15.2 +/- 3.0 mg/kg/d versus 13.2 +/- 2.6 mg/kg/d, P = 0.05)."	( Comparison of the impact of atorvastatin and simvastatin on apoA-I kinetics in men. Couture, P; Lamarche, B; Mauger, JF; Paradis, ME, 2005)	0.93
"Treatment with simvastatin had no effect on serum cholesterol levels in either normal or hypercholesterolemic mice."	( Treatment with simvastatin suppresses the development of experimental abdominal aortic aneurysms in normal and hypercholesterolemic mice. Buckley, C; Ennis, TL; Goeddel, LA; Hawkins, CJ; Mao, D; Shames, ML; Steinmetz, EF; Thompson, RW; Vanvickle-Chavez, SJ, 2005)	1.02
"Treatment with simvastatin suppresses the development of experimental AAAs in both normal and hypercholesterolemic mice. "	( Treatment with simvastatin suppresses the development of experimental abdominal aortic aneurysms in normal and hypercholesterolemic mice. Buckley, C; Ennis, TL; Goeddel, LA; Hawkins, CJ; Mao, D; Shames, ML; Steinmetz, EF; Thompson, RW; Vanvickle-Chavez, SJ, 2005)	1.03
"Treatment with simvastatin significantly reduced the levels of iNOS mRNA and protein in cytokine-treated rat H9c2 cardiac embryonic myoblasts."	( Simvastatin attenuates expression of cytokine-inducible nitric-oxide synthase in embryonic cardiac myoblasts. De Caterina, A; De Caterina, R; Di Napoli, P; Felaco, M; Geng, YJ; Grilli, A; Madonna, R; Massaro, M; Tang, D, 2005)	2.11
"Treatment with simvastatin enhanced the bradykinin-induced endothelium-dependent relaxation in the mesenteric artery, whereas it had no effect on the bradykinin-induced [Ca2+]i elevation in endothelial cells of the aortic valves."	( Long-term inhibition of RhoA attenuates vascular contractility by enhancing endothelial NO production in an intact rabbit mesenteric artery. Hirano, K; Hirano, M; Kanaide, H; Nawata, H; Nishimura, J; Shiga, N, 2005)	0.67
"Treatment with simvastatin also improved neurological deficits and reduced brain edema significantly (P < 0.05)."	( Simvastatin reduced ischemic brain injury and perfusion deficits in an embolic model of stroke. Shabanzadeh, AP; Shuaib, A; Wang, CX, 2005)	2.11
"Treatment with simvastatin for only 3 days results in a 24% drop in the LDL-C level. "	( Cholesterol levels after 3 days of high-dose simvastatin in patients at moderate to high risk for coronary events. Citkowitz, E; Michelena, HI; Osorio, LA, 2005)	0.94
"Treatment with simvastatin, a hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, for 24 hours attenuated the transient [Ca2+]i elevation induced by thrombin. "	( Rac1 regulation of surface expression of protease-activated receptor-1 and responsiveness to thrombin in vascular smooth muscle cells. Bi, D; Hirano, K; Hirano, M; Iwamoto, Y; Kanaide, H; Nishimura, J; Yufu, T, 2005)	0.68
"Treatment with simvastatin decreased lens Ubs of both SD and CT rats by about 20%."	( Concentration and distribution of ubiquinone (coenzyme Q), the endogenous lipid antioxidant, in the rat lens: effect of treatment with simvastatin. Cenedella, RJ; Neely, AR; Sexton, P, 2005)	0.87
"Pretreatment with simvastatin reduces the severity of acute lung injury induced by intestinal I/R in rats."	( Pretreatment with simvastatin reduces lung injury related to intestinal ischemia-reperfusion in rats. Aldemir, D; Arslan, G; Candan, S; Ozen, O; Pirat, A; Yücel, M; Zeyneloglu, P, 2006)	0.99
"Treatment with simvastatin effectively reduced the elevated levels of TG-rich lipoproteins and improved LDL composition in patients with type 2 diabetes. "	( The effect of simvastatin on triglyceride-rich lipoproteins in patients with type 2 diabetic dyslipidemia: a SILHOUETTE trial sub-study. Battisti, WP; Dobs, A; Miller, M; Palmisano, J; Yuan, Z, 2006)	1.05
"Pre-treatment with simvastatin abolished the ischemia-induced activation of NF-kB observed in vehicle-treated animals."	( Activation of NF-kB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment. Banfi, C; Brioschi, M; Cimino, M; Gelosa, P; Gianella, A; Guerrini, U; Nobili, E; Paoletti, R; Sironi, L; Tremoli, E, 2006)	0.88
"Treatment with simvastatin showed a significant decrement in plasma total cholesterol, LDL cholesterol and triglyceride levels (p<0.05). "	( Simvastatin treatment improves endothelial function and increases fibrinolysis in patients with hypercholestrolemia. Aksoyek, S; Atalar, E; Beyazit, Y; Guven, GS; Haznedaroglu, IC; Kekilli, M; Kilicarslan, A; Oz, G; Ozer, N; Sahiner, L; Sozen, T; Yavuz, B, 2006)	2.13
"Treatment with simvastatin led to a significant reduction (P < .005) of total and low-density lipoprotein cholesterol."	( Simvastatin does not exhibit therapeutic anti-inflammatory effects in asthma. Barnes, M; Fleming, D; Lipworth, BJ; Meldrum, KT; Menzies, D; Nair, A, 2007)	2.12
"Pre-treatment with simvastatin, a clinically relevant statin that penetrates the brain, protected against Abeta(1-42) induced synapse damage and neuronal death in vitro."	( Squalestatin protects neurons and reduces the activation of cytoplasmic phospholipase A2 by Abeta(1-42). Bate, C; Williams, A, 2007)	0.66
"Treatment with simvastatin was associated with a significant reduction in mean (SD) membrane lipid peroxidation both preoperatively and at 24 hours postoperatively compared with placebo (preoperative MDA: 0.07 [0.01] vs 0.10 [0.02] nmol/mL, respectively; P < 0.05; postoperative MDA: 0.10 [0.04] vs 0.21 [0.01] nmol/mL; P < 0.05)."	( The effect of simvastatin on erythrocyte membrane fluidity during oxidative stress induced by cardiopulmonary bypass: a randomized controlled study. Chello, M; Coccia, R; Covino, E; Foppoli, C; Lusini, M; Perluigi, M; Spadaccio, C, 2007)	1.04
"Pre-treatment with simvastatin significantly attenuated the CRP-induced CD32 expression and NF-kappaB activation in human umbilical vein endothelial cells. "	( Simvastatin inhibits C-reactive protein-induced pro-inflammatory changes in endothelial cells by decreasing mevalonate pathway products. Lai, LP; Liang, YJ; Shyu, KG; Wang, BW, 2008)	2.12
"Treatment with simvastatin significantly attenuated RhoA activation in the kidney cortices of db/db mice and resulted in a significant reduction of albuminuria and mesangial matrix expansion."	( Targeting of RhoA/ROCK signaling ameliorates progression of diabetic nephropathy independent of glucose control. Danesh, FR; Kolavennu, V; Peng, H; Wang, Y; Zeng, L, 2008)	0.69
"Treatment with simvastatin concentration-dependently inhibited platelet aggregation induced by collagen or arachidonic acid with an IC(50) range of 52-158 microM. "	( Enhanced nitric oxide and cyclic GMP formation plays a role in the anti-platelet activity of simvastatin. Chou, TC; Chu, KM; Lin, YF; Wu, WC, 2008)	0.92
"Rats treated with simvastatin exhibited a significant increase in media thickness and a significant reduction in aneurysmal size compared with control rats. "	( Simvastatin suppresses the progression of experimentally induced cerebral aneurysms in rats. Aoki, T; Hashimoto, N; Ishibashi, R; Kataoka, H; Nozaki, K, 2008)	2.12
"Treatment with simvastatin suppresses the development of CAs by inhibiting inflammatory reactions in aneurysmal walls. "	( Simvastatin suppresses the progression of experimentally induced cerebral aneurysms in rats. Aoki, T; Hashimoto, N; Ishibashi, R; Kataoka, H; Nozaki, K, 2008)	2.14
"Pretreatment with simvastatin could attenuate these changes and reverse this electrical remodeling without lowering the serum cholesterol level, contributing to the ionic mechanism of statin in treatment of arrhythmia independent of a decrease in cholesterol."	( Cardioprotective effects of simvastatin on reversing electrical remodeling induced by myocardial ischemia-reperfusion in normocholesterolemic rabbits. Chen, HX; Ding, C; Fu, XH; He, ZS; Li, JX; Xue, L, 2008)	0.96
"Mice treated with simvastatin, but not fluvastatin, did not demonstrate the prevention of Abeta-induced memory impairment, and showed no significant decrease in oxidative stress."	( Prevention of amyloid beta-induced memory impairment by fluvastatin, associated with the decrease in amyloid beta accumulation and oxidative stress in amyloid beta injection mouse model. Kurinami, H; Morishita, R; Ogihara, T; Sato, N; Shimamura, M; Shinohara, M; Takeda, S; Takeuchi, D, 2008)	0.67
"Treatment with simvastatin in increasing doses over a period of three months (13 patients received 40 mg/day and 5 patients 20 mg/day at the end of the third month) reduced LDL-cholesterol in both groups of patients (35% and 54%) as well as apolipoprotein B (apoB) (31% and 46%) significantly, but Lp(a) levels were not influenced (57 +/- 21 vs 59 +/- 20 and 50 +/- 14 vs 53 +/- 16 mg/dl, respectively)."	( Effects of simvastatin on lipoprotein (a) and lipoprotein composition in patients with nephrotic syndrome. Böhler, J; Eckardt, HG; Schollmeyer, P; Wanner, C; Wieland, H, 1994)	1.02
"Treatment with simvastatin did not change delta 6 desaturation in either phenotype but increased delta 5 desaturation in obese rats to reach the unchanged rate observed in lean animals."	( Effect of simvastatin on desaturase activities in liver from lean and obese Zucker rats. Bézard, J; Blond, JP; Georges, B; Maniongui, C, 1993)	1.03
"Treatment with simvastatin reduced plasma cholesterol level by 16% (mean +/- SEM, 8.1 +/- 0.8 v 6.8 +/- 0.8 mmol/L; P < .05) and plasma apolipoprotein (apo) B level by 19% (1.6 +/- 0.2 v 1.3 +/- 0.2 g/L; P < .05)."	( Simvastatin improves chylomicron remnant removal in familial combined hyperlipidemia without changing chylomicron conversion. Cabezas, MC; de Bruin, TW; Erkelens, DW; Jansen, H; Kock, LA; Kortlandt, W; Van Linde-Sibenius Trip, M, 1993)	2.07
"Rats treated with simvastatin or pravastatin exhibited a reduction in the incorporation of [2-(14)C] acetate into liver cholesterol and displayed lower plasma mevalonate levels as compared to control animals."	( Inhibition of cholesterol synthesis and hepatic 3-hydroxy-3-methylglutaryl--CoA reductase in rats by simvastatin and pravastatin. Del Puppo, M; Galli Kienle, M; Rauli, S, 1995)	0.83
"Treatment with simvastatin was associated with an increase in the arachidonic acid content of the erythrocyte membrane from 12.2 to 15.3 mole% (P < 0.05)."	( Effects of HMG-CoA reductase inhibition on erythrocyte membrane cholesterol and acyl chain composition. Dwight, JF; Hendry, BM; Mendes Ribeiro, AC, 1996)	0.63
"Treatment with simvastatin modulated most of the altered parameters affected during HC that might be, in part, due to inhibition of cholesterol biosynthesis."	( Efficacy of simvastatin and pumpkin-seed oil in the management of dietary-induced hypercholesterolemia. Abd el Latif, HA; Abd el-Fattah, AA; al-Zuhair, H, 1997)	1.02
"Treatment with simvastatin 20 mg daily for 9 days decreased both variables by approximately 50%, the nadir of plasma MVA occurring on the second day and of the L/C ratio on the fifth day, and resulted in a 39% reduction in low-density lipoprotein (LDL)-cholesterol."	( Use of cholesterol precursors to assess changes in cholesterol synthesis under non-steady-state conditions. Kim, KD; Naoumova, RP; Pfohl, M; Thompson, GR, 1998)	0.64
"Treatment with simvastatin decreased the rapid reappearance of total cholesterol noted during the first 2 days after lipid removal but without any major effect on the subsequent reaccumulation of cholesterol."	( Weekly versus biweekly lipid removal and effect of statins in severe hypercholesterolemia. Bianchetti, MG; Nuoffer, JM; Pfammatter, JP; Wiesmann, UN; Zenklusen, JM, 1998)	0.64
"Treatment with simvastatin 20 mg/d for 12 weeks (n = 194) resulted in significantly greater reductions in plasma total cholesterol and low-density lipoprotein cholesterol levels (25.7% and 33.6%, respectively) compared with pravastatin 40 mg/d for 12 weeks (n = 193) (19.0% and 26.3%, respectively) (P<0.001)."	( Double-masked comparison of the quality of life of hypercholesterolemic men treated with simvastatin or pravastatin. International Quality of Life Multicenter Group. Seed, M; Weir, MR, 1999)	0.86
"Pretreatment with simvastatin (1 microg/ml) reduced total cholesterol content in SMC."	( Simvastatin enhanced sodium nitroprusside-induced apoptosis of smooth muscle cells. An involvement of geranylgeraniol. Fujita, H; Ishikawa, K; Morita, I; Murota, S; Shimotsuura, S; Yanagisawa, A, 2000)	2.07
"Treatment with simvastatin for patients with cardiovascular disease is cost-effective for men and women, with or without diabetes."	( Cost-effectiveness of treating hyperlipidemia in the presence of diabetes : who should be treated? Coupal, L; Dorais, M; Grover, SA; Zowall, H, 2000)	0.65
"Treatment with simvastatin causes a reduction of events of new-onset heart failure, but this may be attributable to properties other than its lipid-lowering effects."	( The endotoxin-lipoprotein hypothesis. Anker, SD; Coats, AJ; Rauchhaus, M, 2000)	0.65
"Treatment with simvastatin significantly reduced fasting and postprandial remnant lipoprotein cholesterol concentrations (13+/-3 mg/dL and 136+/-53 mg."	( High dose of simvastatin normalizes postprandial remnant-like particle response in patients with heterozygous familial hypercholesterolemia. Cabezas, MC; Dallinga-Thie, GM; de Valk, HW; Erkelens, DW; Jansen, H; Schreuder, PC; Twickler, TB, 2000)	1.02
"Treatment with simvastatin (20-80 mg) produced statistically significant improvements in all measured lipid variables by the end of the study."	( Attaining United States and European guideline LDL-cholesterol levels with simvastatin in patients with coronary heart disease (the GOALLS study). Adams, PC; Brown, AS; Garmendia, F; Reiber, I, 2000)	0.88
"Treatment with simvastatin or bezafibrate in addition to HRT should be considered in cases of postmenopausal hypercholesterolemia in which HRT alone fails to lower the serum lipoprotein levels."	( Effects of bezafibrate and simvastatin on plasma lipoproteins in hypercholesterolemia resistant to hormone replacement therapy. Adachi, K; Azuma, C; Hayakawa, J; Ikegami, H; Kurachi, H; Matumoto, K; Morishige, K; Murata, Y; Nishio, Y; Node, K; Ohmichi, M; Tasaka, K, 2001)	0.96
"Treatment with simvastatin 40 and 80 mg/day, but not atorvastatin 20 and 40 mg/day, led to significant (p < 0.05) reductions in BSAP in both men (4.1-5.4% reduction) and women (4.2-7.4% reduction)."	( Effects of statins on biomarkers of bone metabolism: a randomised trial. Farnier, M; Mercuri, M; Stein, EA; Waldstreicher, J, 2001)	0.65
"Treatment with simvastatin had favorable effects on the lipid profile, producing significant percentage changes from baseline in all parameters (P < 0.001)."	( STATT: a titrate-to-goal study of simvastatin in Asian patients with coronary heart disease. Simvastatin Treats Asians to Target. Cai, NS; Cho, SY; Choi, DH; Chung, N; Fan, WF; Koh, KK; Lee, K; Lee, PY; Lee, S; Lee, SH; Panchavinnin, P; Phankingthongkum, R; Sangwatanaroj, S; Son, JW; Wang, JJ; Yin, WH; Young, MS; Zhu, JR, 2001)	0.93
"Treatment with simvastatin decreased fasting and postprandial C3 by 6% and 39%, respectively (P<0.05 for both versus no treatment)."	( Postprandial increase of complement component 3 in normolipidemic patients with coronary artery disease: effects of expanded-dose simvastatin. Castro Cabezas, M; de Jaegere, PP; Erkelens, DW; Halkes, CJ; Plokker, HW; van Der Helm, Y; van Dijk, H, 2001)	0.86
"Pretreatment with simvastatin attenuated myocardial injury after 30 minutes of myocardial ischemia and 24 hours of reperfusion."	( Pretreatment with simvastatin attenuates myocardial dysfunction after ischemia and chronic reperfusion. Jones, SP; Lefer, DJ; Trocha, SD, 2001)	0.97
"Treatment by simvastatin or cerivastatin restored impaired metabolism of exogenous ATP and ADP in thrombin-activated endothelial cells by preventing thrombin-induced downregulation of CD39/ATPDase."	( Reversal of thrombin-induced deactivation of CD39/ATPDase in endothelial cells by HMG-CoA reductase inhibition: effects on Rho-GTPase and adenosine nucleotide metabolism. Balduini, CL; Dunzendorfer, S; Egger, P; Gritti, D; Kaneider, NC; Noris, P; Ricevuti, G; Wiedermann, CJ, 2002)	0.67
"Treatment with simvastatin (40 mg/d) effectively lowered LDL-C by 34.3% (P < 0.001)."	( Lowering low density lipoprotein cholesterol with simvastatin, a hydroxy-3-methylglutaryl-coenzyme a reductase inhibitor, does not affect luteal function in premenopausal women. Burkman, R; Liu, M; Miller, S; Mitchel, Y; Nakajima, S; Peskin, E; Plotkin, D; Richardson, D; Santoro, N; Shapiro, D; Waldstreicher, J, 2002)	0.91
"Treatment with simvastatin reduced concentrations of LDL cholesterol to 194, 168 and 156 mg/dl, respectively, on doses of 20, 40 and 80 mg/day."	( Comparative hypolipidemic effects of lovastatin and simvastatin in patients with heterozygous familial hypercholesterolemia. Bacon, S; Illingworth, DR; Pappu, AS; Sexton, GJ, 1992)	0.87
"Treatment with simvastatin, an inhibitor of cholesterol synthesis, reverses the hyperlipidaemia and enables o,p'DDD therapy to be maintained without increasing cardiovascular risk."	( Possible mechanism and treatment of o,p'DDD-induced hypercholesterolaemia. Anderson, JV; Besser, GM; Maher, VM; Scoppola, A; Thompson, GR; Trainer, PJ, 1992)	0.62
"On treatment with simvastatin 10 mg O.D., the plasma HDL2b and HDL3a concentrations increased by 30% (P less than 0.001) and 12% (P less than 0.01) respectively."	( Plasma high density lipoprotein particle size alteration by simvastatin treatment in patients with hypercholesterolaemia. Johansson, J; Mölgaard, J; Olsson, AG, 1991)	0.85
"Treatment with simvastatin or gemfibrozil in hypertensive patients in hydrochlorothiazide monotherapy can reduce total cholesterol and LDL-cholesterol plasma levels, while significantly increasing HDL plasma levels compared to placebo."	( [Simvastatin versus gemfibrozil in the treatment of primary hypercholesterolemia in hypertensive patients treated with hydrochlorothiazide]. Bentivoglio, M; Berioli, S; Conti, R; Corea, L; Osanna, RA; Savino, K; Zollino, L, 1990)	1.53
"Treatment with simvastatin reduced cholesterol levels from 6.85 to 4.75 mmol/l (P less than 0.001), triglycerides from 2.7 to 2.1 mmol/l (P less than 0.01), low-density lipoproteins from 4.6 to 2.6 mmol/l (P less than 0.001) and high-density lipoproteins rose from 1.09 to 1.18 mmol/l (P less than 0.01)."	( Simvastatin in the treatment of hypercholesterolaemia in patients with essential hypertension. Anderson, A; Hopper, J; Macaskill, G; McDonald, P; Morgan, T, 1990)	2.06
"Treatment with simvastatin decreases the atherogenic potential of plasma more than cholestyramine monotherapy and causes fewer adverse effects."	( Clinical experience with simvastatin compared with cholestyramine. Baggen, MG; Erkelens, DW; Kettner, M; Koningsberger, JC; Mol, MJ; Van Doormaal, JJ, 1988)	0.92

Toxicity

Simvastatin is an effective and safe drug with excellent tolerability. It comprises a safe and efficient choice for dyslipidemia treatment in high-risk and diabetic patients. The Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 142 reports of suspected adverse reactions to simvastATins.

Excerpt	Reference	Relevance
"to investigate the symptomatic and biochemical side effect profile of simvastatin (a new cholesterol lowering drug) following routine use in a specialist hospital outpatient clinic."	( Simvastatin and side effects. Lintott, CJ; Scott, RS; Wilson, MJ, 1991)	1.96
" It is concluded that simvastatin is a safe and efficient cholesterol-lowering drug for long-term therapy, both as a single drug and in combination with cholestyramine."	( Long-term efficacy and safety of simvastatin alone and in combination therapy in treatment of hypercholesterolaemia. Lundh, BL; Mölgaard, J; Olsson, AG; von Schenck, H, 1991)	0.88
" The most frequently reported drug-related clinical adverse experiences were constipation (2."	( Long-term safety and efficacy profile of simvastatin. Bocanegra, TS; Boccuzzi, SJ; Keegan, ME; Shapiro, DR; Walker, JF, 1991)	0.55
" The most serious side-effect in our study was myolysis which occurred in two patients with a marked increase in creatine phosphokinase."	( Efficacy and safety of simvastatin (alone or in association with cholestyramine). A 1-year study in 66 patients with type II hyperlipoproteinaemia. Aubert, I; Bauduceau, B; Chanu, B; Dachet, C; Emmerich, J; Erlich, D; Gautier, D; Jacotot, B; Rouffy, J, 1990)	0.59
" No consistent adverse clinical or biochemical effects were observed during the three-year therapy."	( [Evaluation of tolerance, efficacy and safety of 3-year simvastatin use in the treatment of primary hypercholesterolemia]. Bercher, L; Bovet, P; Brunner, HR; Darioli, R, 1990)	0.53
" Our observations provide good evidence that lovastatin and simvastatin have no undesirable toxic effects on the lens and other ocular tissues, compared with fenofibrate."	( Ocular drug safety and HMG-CoA-reductase inhibitors. Hockwin, O; Paulus, U; Schmidt, J; Schmitt, C; von Bergmann, K, 1994)	0.53
""Is there any safe and optimal treatment of hyperlipidemia following heart transplantation?" The problem of hypercholesterolemia following heart transplantation if often underestimated."	( [Can hyperlipidemia after heart transplantation be optimally and safely treated?]. Arndtz, N; Reichart, B; Seidel, D; Thiery, J; Wenke, K, 1994)	0.29
" There were no differences between the treatment groups in the numbers of reports of 'possible adverse effects' of treatment or of a range of different symptoms or conditions (including those related to sleep or mood) recorded at regular clinic follow-up."	( Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study. Armitage, J; Collins, R; Fatemian, M; Kearney, E; Keech, A; Lawson, A; Lyon, V; MacMahon, S; Mindell, J; Wallendszus, K, 1994)	0.51
" This short-term study showed few adverse effects for both drugs."	( Comparative efficacy and safety of micronized fenofibrate and simvastatin in patients with primary type IIa or IIb hyperlipidemia. Bonnefous, F; Debbas, N; Farnier, M; Irvine, A, 1994)	0.53
" Adverse experiences were mild and did not differ between treatment groups; in each group, one subject discontinued medication because of complaints of dizziness."	( Treatment of primary hypercholesterolaemia. Short-term efficacy and safety of increasing doses of simvastatin and pravastatin: a double-blind comparative study. De Haan, AF; Kastelein, JJ; Kortmann, B; Kroon, AA; Lansberg, PJ; Stalenhoef, AF; Stuyt, PM, 1993)	0.5
" Compliance with prescribed medication was very good and the drug was well tolerated; only 3% of patients manifested a clinical adverse experience requiring discontinuation or a clinical adverse experience described as serious (associated with hospitalization or serious disability)."	( Simvastatin in severe primary hypercholesterolemia: efficacy, safety, and tolerability in 595 patients over 18 weeks. The Principal Investigators. Simons, LA, 1993)	1.73
"Between December 1989 and December 1992, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 142 reports of suspected adverse reactions to simvastatin or pravastatin."	( [Side effects of cholesterol synthesis inhibitors]. Stricker, BH; Wolterbeek, R, 1993)	0.48
" There was no significant difference between groups in the frequency of drug-related adverse experiences."	( Comparison of the efficacy, safety and tolerability of simvastatin and pravastatin for hypercholesterolemia. The Simvastatin Pravastatin Study Group. , 1993)	0.53
" Relevant data on the incidence of adverse effects are presented."	( Comparative evaluation of the safety and efficacy of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. Hsu, I; Johnson, NE; Spinler, SA, )	0.13
"We sought to identify differences in the description of adverse drug experiences in reports of randomized clinical trials (RCTs) from the United States and Japan, using diclofenac and simvastatin as test drugs."	( Japanese and American reports of randomized trials: differences in the reporting of adverse effects. Hayashi, K; Walker, AM, 1996)	0.49
"Oxidized low density lipoproteins (OxLDL) are toxic to cells of the arterial wall and trigger the expression of the inducible form of hsp 70 in cultured endothelial cells (EAhy-926) and smooth muscle cells (HUVSMC)."	( Simvastatin modulates the heat shock response and cytotoxicity mediated by oxidized LDL in cultured human endothelial smooth muscle cells. Catapano, AL; Jacoviello, C; Longoni, C; Pirillo, A; Radaelli, A, 1997)	1.74
" No serious adverse events were considered associated with treatment."	( A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia. Best, J; Black, D; Bracs, P; d'Emden, M; Dart, A; Hamilton-Craig, I; Jerums, G; Nicholson, G; Sullivan, D; Tallis, G; West, M, 1997)	0.51
" Results of this study confirmed that a low dose (10 mg) of simvastatin daily is a safe and effective method of reducing plasma levels of total and low-density lipoprotein cholesterol in hypercholesterolemic, hypertensive elderly patients receiving concurrent antihypertensive drug therapy, and that it has the additional potential benefit of reducing plasma levels of insulin."	( Short-term safety and efficacy of low-dose simvastatin in elderly patients with hypertensive hypercholesterolemia and fasting hyperinsulinemia. Chan, P; Huang, TY; Lee, C; Lee, YS; Tomlinson, B, 1997)	0.8
" Physical and laboratory investigations for adverse effects were performed every month for the first 3 months and every 3 months thereafter."	( Safety and efficacy of long-term statin-fibrate combinations in patients with refractory familial combined hyperlipidemia. Athyros, VG; Carina, MV; Didangelos, TP; Hatzikonstandinou, HA; Kontopoulos, AG; Kranitsas, DF; Papageorgiou, AA, 1997)	0.3
" Atorvastatin was well-tolerated, and no serious or medically important adverse events were observed."	( Efficacy and safety of a new cholesterol synthesis inhibitor, atorvastatin, in comparison with simvastatin and pravastatin, in subjects with hypercholesterolemia. Black, DM; Mahla, G; Muller, D; Pentrup, A; Wolffenbuttel, BH, 1998)	0.52
"We conclude that atorvastatin is a safe and very efficacious cholesterol-lowering agent, which also possesses significant triglyceride-lowering properties."	( Efficacy and safety of a new cholesterol synthesis inhibitor, atorvastatin, in comparison with simvastatin and pravastatin, in subjects with hypercholesterolemia. Black, DM; Mahla, G; Muller, D; Pentrup, A; Wolffenbuttel, BH, 1998)	0.52
" There was no significant difference between the incidence of adverse effects with cerivastatin and comparator statins or between cerivastatin and other statins with respect to clinically significant increases in either hepatic enzymes or creatine phosphokinase."	( Clinical efficacy and safety of cerivastatin: summary of pivotal phase IIb/III studies. Davignon, J; Hanefeld, M; Hunninghake, DB; Insull, W; Nakaya, N; Ose, L, 1998)	0.3
" Gemfibrozil treatment was also withdrawn significantly more frequently due to a possible adverse reaction compared with the other two drugs."	( A comparison of the use, effectiveness and safety of bezafibrate, gemfibrozil and simvastatin in normal clinical practice using the New Zealand Intensive Medicines Monitoring Programme (IMMP). Beggs, PW; Clark, DW; Coulter, DM; Williams, SM, 1999)	0.53
"In normal clinical practice in New Zealand gemfibrozil appears less effective and more frequently causes adverse effects leading to withdrawal of treatment than either bezafibrate or simvastatin."	( A comparison of the use, effectiveness and safety of bezafibrate, gemfibrozil and simvastatin in normal clinical practice using the New Zealand Intensive Medicines Monitoring Programme (IMMP). Beggs, PW; Clark, DW; Coulter, DM; Williams, SM, 1999)	0.72
" This 10-year study demonstrates that simvastatin is an effective and safe drug with excellent tolerability with only few minor side effects, and causes a pronounced and persistent cholesterol-lowering effect during long-term treatment of hypercholesterolemic patients at risk."	( Efficacy and safety of simvastatin for high-risk hypercholesterolemia. Mölgaard, J; Olsson, AG; Wärjerstam-Elf, S, 1999)	0.89
" Treatments were well tolerated, and the incidence of adverse effects was similar in both groups."	( Efficacy and safety of cerivastatin in primary hypercholesterolemia: a long term comparative titration study with simvastatin. Hanna, K; Leiter, LA, 1999)	0.51
" Adverse event rates were statistically equivalent (p<0."	( Safety of low-density lipoprotein cholestrol reduction with atorvastatin versus simvastatin in a coronary heart disease population (the TARGET TANGIBLE trial). Klein, G; März, W; Neiss, A; Wehling, M; Wollschläger, H, 1999)	0.53
" The frequency of treatment-associated adverse events (AEs) in the atorvastatin LDL-C < or =80 mg/dl (2."	( Safety profile of atorvastatin-treated patients with low LDL-cholesterol levels. Bakker-Arkema, RG; Black, DM; Nawrocki, JW, 2000)	0.31
" No new or unexpected adverse events were observed and the overall clinical event profiles were similar in the two groups."	( Lipid-altering efficacy and safety of simvastatin 80 mg/day: worldwide long-term experience in patients with hypercholesterolemia. Bays, H; Bertolami, M; Campodónico, S; Davidson, MH; Dujovne, CA; Escobar, ID; Hunninghake, DB; Insull, W; Kastelein, JJ; Kush, D; Melino, MR; Mercuri, M; Mitchel, YB; Ose, L; Schrott, HG; Scott, RS; Stein, EA; Stepanavage, ME; Tate, AC; Weiss, SR; Wu, M, 2000)	0.58
" Fewer than 6% of patients in either treatment group experienced drug-attributable adverse events, which were mostly mild to moderate in nature."	( Comparison of efficacy and safety of atorvastatin (10mg) with simvastatin (10mg) at six weeks. ASSET Investigators. Goldner, D; Insull, W; Kafonek, S; Zieve, F, 2001)	0.55
" Adverse events occurred in 3% of patients, and included myositis (0."	( Lipid-lowering efficacy, safety, and costs of a large-scale therapeutic statin formulary conversion program. Gibbs, H; Grace, K; Hyatt, R; Jones, DL; Lowenthal, SP; Maneval, K; O'Malley, PG; Sheikh, M; Spain, J; Swiecki, J; Taylor, AJ; West, M, 2001)	0.31
" The possibility of uncommon but potentially serious adverse effects suggests that these programs require appropriate monitoring."	( Lipid-lowering efficacy, safety, and costs of a large-scale therapeutic statin formulary conversion program. Gibbs, H; Grace, K; Hyatt, R; Jones, DL; Lowenthal, SP; Maneval, K; O'Malley, PG; Sheikh, M; Spain, J; Swiecki, J; Taylor, AJ; West, M, 2001)	0.31
" The incidence of clinical and laboratory adverse experiences were not increased in the simvastatin-treated patients compared with placebo."	( Safety and efficacy of simvastatin in hypercholesterolemic patients undergoing chronic renal dialysis. Morgan, C; Rigby, RJ; Saltissi, D; Westhuyzen, J, 2002)	0.85
" Ezetimibe was safe and well tolerated."	( Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Bruckert, E; Gagné, C; Gaudet, D, 2002)	0.55
" No significant adverse effects were noted, and no complications with drug withdrawals occurred."	( Comparison of the efficacy and safety of pravastatin and simvastatin in heart transplantation. DeGruiter, H; Lavie, CJ; Mehra, MR; Milani, RV; Uber, PA; Vivekananthan, K, 2002)	0.56
"Simvastatin and pravastatin are safe and very effective in total cholesterol and LDL cholesterol lowering in heart transplant recipients, with simvastatin being more efficacious than pravastatin in lipid lowering in this group of patients."	( Comparison of the efficacy and safety of pravastatin and simvastatin in heart transplantation. DeGruiter, H; Lavie, CJ; Mehra, MR; Milani, RV; Uber, PA; Vivekananthan, K, 2002)	2
" Data obtained by monitoring lipid profiles, adverse events, and laboratory tests during the 16 weeks of study were used to assess the efficacy and safety of both treatments."	( Comparing the efficacy and safety of atorvastatin and simvastatin in Asians with elevated low-density lipoprotein-cholesterol--a multinational, multicenter, double-blind study. Hin, AT; Lee, YT; Suyono, S; Sy, R; Tanphaichitr, V; Wu, CC, 2002)	0.56
" No deaths occurred in the study population and the incidence of treatment-emergent adverse events was the same in the two groups (28%)."	( Comparing the efficacy and safety of atorvastatin and simvastatin in Asians with elevated low-density lipoprotein-cholesterol--a multinational, multicenter, double-blind study. Hin, AT; Lee, YT; Suyono, S; Sy, R; Tanphaichitr, V; Wu, CC, 2002)	0.56
" There was no evidence of any adverse effect of simvastatin on growth and pubertal development."	( Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized, double-blind, placebo-controlled trial with simvastatin. Bakker, HD; de Jongh, S; Dobbelaere, D; Gagné, C; Gumbiner, B; Kastelein, JJ; Lambert, M; Mercuri, M; Ose, L; Perron, P; Saborio, M; Sapre, A; Scott, R; Stepanavage, M; Szamosi, T; Tuohy, MB; van Trotsenburg, AS, 2002)	0.77
" Interest lies in estimating relevant doses among those under investigation for efficacy and safety variables, such as the minimum effective dose or the maximum safe dose (or estimating both doses simultaneously)."	( Identifying effective and/or safe doses by stepwise confidence intervals for ratios. Bretz, F; Hothorn, LA; Hsu, JC, 2003)	0.32
" Data included medication use, clinic visits, adverse events, LDL-C and other laboratory measures."	( An economic analysis of the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS). McBurney, CR; Smith, DG, 2003)	0.32
" In all five studies, most adverse events were related to hypoglycemia, as expected in a normal population given a blood glucose regulator."	( Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide. Hansen, KT; Hatorp, V; Thomsen, MS, 2003)	0.32
"To investigate whether patients, who are at risk of major acute coronary events, are safe to undergo and benefit from early intervention after using simvastatin."	( Lipid-lowering efficacy and safety of varying doses of Simvastatin in patients with early stage acute coronary syndromes: one-year follow-up study. Cui, L; Gao, M; Hu, D; Liu, X; Wei, Y; Xu, Z; Yang, X; Zou, Y, 2003)	0.77
" Lipid levels were measured immediately, followed by the 3rd, 6th and 12th month after admission and all adverse events were recorded during follow-up."	( Lipid-lowering efficacy and safety of varying doses of Simvastatin in patients with early stage acute coronary syndromes: one-year follow-up study. Cui, L; Gao, M; Hu, D; Liu, X; Wei, Y; Xu, Z; Yang, X; Zou, Y, 2003)	0.57
"A generic preparation of simvastatin Vasilip in a 12-week open noncomparative study demonstrated substantial lipid lowering activity and did not induce serious adverse reactions."	( [Efficacy and safety of simvastatin in patients with hypercholesterolemia (results of a Multicenter Clinical Study)]. Bubnova, MG; Katel'nitskaia, LI; Kukharchuk, VV; Nikitin, IuP; Ol'binskaia, LI, 2003)	0.93
" How safe and well-tolerated is this combination? One hundred sixty patients with CAD, including 25 with diabetes mellitus, with mean low-density lipoprotein cholesterol of 128 mg/dl, HDL cholesterol of < or =35 mg/dl (mean 31), and mean triglycerides of 217 mg/dl were randomized to 4 factorial combinations of antioxidant vitamins or their placebos and simvastatin plus niacin or their placebos."	( Safety and tolerability of simvastatin plus niacin in patients with coronary artery disease and low high-density lipoprotein cholesterol (The HDL Atherosclerosis Treatment Study). Albers, JJ; Brown, BG; Chait, A; DeAngelis, D; Dowdy, AA; Frohlich, J; Heise, N; Morse, JS; Zhao, XQ, 2004)	0.79
"The estimated likelihood of the side effect occurring."	( Comparison of two methods of presenting risk information to patients about the side effects of medicines. Berry, DC; Knapp, P; Raynor, DK, 2004)	0.32
"The mean likelihood estimate given for the constipation side effect was 34."	( Comparison of two methods of presenting risk information to patients about the side effects of medicines. Berry, DC; Knapp, P; Raynor, DK, 2004)	0.32
" The use of verbal descriptors to improve the level of information about side effect risk leads to overestimation of the level of harm and may lead patients to make inappropriate decisions about whether or not they take the medicine."	( Comparison of two methods of presenting risk information to patients about the side effects of medicines. Berry, DC; Knapp, P; Raynor, DK, 2004)	0.32
" Safety and tolerability were assessed by monitoring adverse experiences and safety laboratory tests."	( Efficacy and safety of simvastatin in Asian and non-Asian coronary heart disease patients: a comparison of the GOALLS and STATT studies. Bilheimer, D; Chung, N; Davies, MJ; Lee, K; Loeys, T; Morales, D; Sangwatanaroj, S; Shah, A; Yin, WH; Zhu, JR, 2004)	0.63
" There were no clinically meaningful differences between the EZE and PBO groups with regard to the incidence of treatment-related adverse events (AEs) (19% vs 17%, respectively), discontinuations due to AEs (7% vs 10%), serious AEs (12% vs 17%), consecutive elevations in liver function tests > or =3 times the upper limit of normal (ULN) (0."	( Long-term safety and, tolerability profiles and lipid-modifying efficacy of ezetimibe coadministered with ongoing simvastatin treatment: a multicenter, randomized, double-blind, placebo-controlled, 48-week extension study. Cho, M; Gagné, C; Gumbiner, B; Johnson-Levonas, AO; Masana, L; Mata, P; Meehan, A; Sirah, W; Troxell, JK, 2005)	0.54
"The authors reviewed adverse events (AEs) reported to the United States Food and Drug Administration to determine the percentage of statin-associated AE reports with concurrent amiodarone use for simvastatin, atorvastatin, and pravastatin."	( Adverse events with concomitant amiodarone and statin therapy. Alsheikh-Ali, AA; Karas, RH, 2005)	0.52
" Lipid profiles, physical and laboratory investigations for adverse effects were assessed."	( [Efficacy and safety of combination therapy with simvastatin and fenofibrate for combined hyperlipidemia]. Chen, H; Luo, Y; Ren, JY, 2005)	0.58
" (3) All treatments were well tolerated with no increase in adverse events for combination therapy versus monotherapy."	( [Efficacy and safety of combination therapy with simvastatin and fenofibrate for combined hyperlipidemia]. Chen, H; Luo, Y; Ren, JY, 2005)	0.58
"The results of this study demonstrated that combination therapy with fenofibrate (200 mg/day) and low-dose simvastatin (10 mg/day) is more effective than monotherapy in patients with combined hyperlipidemia, and is generally safe and well tolerated."	( [Efficacy and safety of combination therapy with simvastatin and fenofibrate for combined hyperlipidemia]. Chen, H; Luo, Y; Ren, JY, 2005)	0.8
" The clinical benefits of preventing vascular events, myocardial infarction, stroke, and need for revascularization outweigh the low rates of adverse events associated with high-dose statin therapy in high- and intermediate-risk patients."	( Safety of high-dose atorvastatin therapy. Waters, DD, 2005)	0.33
" At least 1 clinical adverse event and at least 1 adverse drug reaction were observed in 25."	( A randomized, open-label study to evaluate the efficacy and safety of pitavastatin compared with simvastatin in Korean patients with hypercholesterolemia. Cho, SY; Chung, N; Ha, JW; Kang, HJ; Oh, BH; Park, S; Rim, SJ, 2005)	0.55
" Seventeen subjects who had adverse drug reactions (ADRs) to simvastatin (ADR group) could not complete the 6-month follow-up and were included in the association analyses for safety."	( The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment. da Silveira, FR; Ferreira, ME; Fiegenbaum, M; Hutz, MH; Pires, RC; Van der Sand, CR; Van der Sand, LC, 2005)	0.78
"Myopathy and rhabdomyolysis are rare adverse effects of treatment with hydroxymethylglutaryl-coA reductase inhibitors."	( [Rhabdomyolysis as a side effect of simvastatin treatment]. Iskra, B; Kes, P; Zivko, M, 2005)	0.6
"Despite the excellent benefit/risk profile of statins, their use is limited by a dose-related risk of adverse events, particularly those related to muscle toxicity."	( Striated muscle safety of ezetimibe/simvastatin (Vytorin). Davidson, MH; Maccubbin, D; Musliner, T; Stepanavage, M; Strony, J, 2006)	0.61
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."	( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling. Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004)	0.32
" There were no serious adverse events caused by study treatment."	( The second United Kingdom Heart and Renal Protection (UK-HARP-II) Study: a randomized controlled study of the biochemical safety and efficacy of adding ezetimibe to simvastatin as initial therapy among patients with CKD. Adu, D; Altmann, P; Armitage, J; Baigent, C; Ball, S; Baxter, A; Blackwell, L; Cairns, HS; Carr, S; Collins, R; Kourellias, K; Landray, M; Leaper, C; Rogerson, M; Scoble, JE; Tomson, CR; Warwick, G; Wheeler, DC, 2006)	0.53
" Tolerability was assessed by adverse event reports and laboratory and vital signs assessments throughout the study."	( Comparison of the lipid-modifying efficacy and safety profiles of ezetimibe coadministered with simvastatin in older versus younger patients with primary hypercholesterolemia: a post Hoc analysis of subpopulations from three pooled clinical trials. Davidson, M; Feldman, T; Maccubbin, D; Meehan, A; Mitchel, Y; Shah, A; Tribble, D; Veltri, E; Zakson, M, 2006)	0.55
" Clinical chemistry profiles and proportions of adverse events were similar in both groups at baseline and follow-up."	( Efficacy, safety and LDL-C goal attainment of ezetimibe 10 mg-simvastatin 20 mg vs. placebo-simvastatin 20 mg in UK-based adults with coronary heart disease and hypercholesterolaemia. Hughes, EA; Patel, JV, 2006)	0.57
" However, clinical data consistently support the view that adverse events are uncommon even when intensive therapy is used to reach aggressive low-density lipoprotein cholesterol goals."	( How safe is aggressive statin therapy? Guthrie, RM, 2006)	0.33
" Pravastatin was not toxic up to 1 mmol/l."	( Toxicity of statins on rat skeletal muscle mitochondria. Brecht, K; Kaufmann, P; Krähenbühl, S; Török, M; Waldhauser, KM; Zahno, A, 2006)	0.33
" Current drug labeling warns of an increased risk of adverse events with statin and niacin combinations."	( Safety of lovastatin/extended release niacin compared with lovastatin alone, atorvastatin alone, pravastatin alone, and simvastatin alone (from the United States Food and Drug Administration adverse event reporting system). Alsheikh-Ali, AA; Karas, RH, 2007)	0.55
" 100 patients received 20-40 mg Zo-20 during the 3 months period, all parameters of the blood plasma lipids and adverse events were monitored during the study."	( [Clinical efficacy and safety of Zo-20 in patients with ischemic heart disease]. Mamatsashvili, M; Mdivani, I, 2008)	0.35
" Niacin's major adverse experience (AE) is flushing."	( Safety of niacin and simvastatin combination therapy. Bays, H, 2008)	0.66
"001) because of clinical adverse experiences (primarily flushing)."	( Lipid-altering efficacy and safety of ezetimibe/simvastatin coadministered with extended-release niacin in patients with type IIa or type IIb hyperlipidemia. Brown, BG; Fazio, S; Guyton, JR; Polis, A; Tershakovec, AM; Tomassini, JE, 2008)	0.6
" A total of 20% of patients discontinued treatment because of a treatment-related adverse event, including 7% who discontinued because of flushing."	( Long-term safety and efficacy of a combination of niacin extended release and simvastatin in patients with dyslipidemia: the OCEANS study. Bajorunas, DR; Davidson, MH; Karas, RH; Kashyap, ML; Keller, LH; Knopp, RH, 2008)	0.57
"Treatment with NER/S 2,000/40 mg/day is well tolerated, has no unanticipated adverse events, and provides additional, clinically relevant improvements in multiple lipid parameters beyond statin monotherapy."	( Long-term safety and efficacy of a combination of niacin extended release and simvastatin in patients with dyslipidemia: the OCEANS study. Bajorunas, DR; Davidson, MH; Karas, RH; Kashyap, ML; Keller, LH; Knopp, RH, 2008)	0.57
" Our results suggest that artemisinin, a widely used antimalarial drug, may impair the response to doxorubicin in colon cancer cells; on the contrary, simvastatin and RhoA siRNA may represent future therapeutic approaches to improve doxorubicin efficacy, reducing the risk of doxorubicin-dependent adverse effects."	( Activation of nuclear factor-kappa B pathway by simvastatin and RhoA silencing increases doxorubicin cytotoxicity in human colon cancer HT29 cells. Aldieri, E; Bosia, A; Costamagna, C; Doublier, S; Ghigo, D; Pescarmona, G; Riganti, C, 2008)	0.8
" In conclusion, this study showed that NER/S provided additional clinically relevant improvements in multiple lipid parameters and was safe and well tolerated."	( Comparison of the safety and efficacy of a combination tablet of niacin extended release and simvastatin vs simvastatin monotherapy in patients with increased non-HDL cholesterol (from the SEACOAST I study). Bajorunas, DR; Ballantyne, CM; Davidson, MH; Karas, RH; Keller, LH; McKenney, J, 2008)	0.57
" These effects were seen without any documented adverse drug reactions or changes in viral and immunologic control."	( Safety and efficacy of simvastatin for the treatment of dyslipidemia in human immunodeficiency virus-infected patients receiving efavirenz-based highly active antiretroviral therapy. Bain, AM; Bedimo, R; Busti, AJ; Eaton, SA; Nguyen, ST; Payne, KD; Rahman, AP, 2008)	0.66
" Incidence of adverse drug reactions during the 4-year extension period was lower than previously."	( Relationship between coronary events and serum cholesterol during 10 years of low-dose simvastatin therapy: long-term efficacy and safety in Japanese patients with hypercholesterolemia in the Japan Lipid Intervention Trial (J-LIT) Extension 10 Study, a pr Itakura, H; Kita, T; Mabuchi, H; Matsuzaki, M; Matsuzawa, Y; Nakaya, N; Oikawa, S; Saito, Y; Sasaki, J; Shimamoto, K, 2008)	0.57
"Long-term, low-dose simvastatin therapy was safe and effective in Japanese patients with hypercholesterolemia."	( Relationship between coronary events and serum cholesterol during 10 years of low-dose simvastatin therapy: long-term efficacy and safety in Japanese patients with hypercholesterolemia in the Japan Lipid Intervention Trial (J-LIT) Extension 10 Study, a pr Itakura, H; Kita, T; Mabuchi, H; Matsuzaki, M; Matsuzawa, Y; Nakaya, N; Oikawa, S; Saito, Y; Sasaki, J; Shimamoto, K, 2008)	0.89
" During the extension study, investigators assessed adverse events (AEs)."	( Long-term (48-week) safety of ezetimibe 10 mg/day coadministered with simvastatin compared to simvastatin alone in patients with primary hypercholesterolemia. Bays, H; Capece, R; Liu, J; Sapre, A; Taggart, W; Tershakovec, A, 2008)	0.58
" Safety and tolerability were assessed through clinical and laboratory adverse experiences (AEs)."	( Long-term safety and tolerability of ezetimibe coadministered with simvastatin in hypercholesterolemic patients: a randomized, 12-month double-blind extension study. Hanson, ME; Strony, J; Veltri, EP; Yang, B, 2008)	0.58
"3-Hydroxy-3-methylglutaryl CoA reductase inhibitors (statins) are safe and well-tolerated therapeutic drugs."	( Possible mechanisms underlying statin-induced skeletal muscle toxicity in L6 fibroblasts and in rats. Ichihara, K; Itagaki, M; Kaneta, S; Kano, S; Satoh, K; Takaguri, A, 2009)	0.35
" Rates of any reported serious adverse event were higher in older patients, but did not differ between the 2 statin groups."	( Comparison of efficacy and safety of atorvastatin (80 mg) to simvastatin (20 to 40 mg) in patients aged <65 versus >or=65 years with coronary heart disease (from the Incremental DEcrease through Aggressive Lipid Lowering [IDEAL] study). Cater, NB; Faergeman, O; Holme, I; Kastelein, JJ; Larsen, ML; Lindahl, C; Olsson, AG; Pedersen, TR; Szarek, M; Tikkanen, MJ, 2009)	0.59
"Muscle and liver adverse effects of simvastatin 40 mg daily were evaluated in a randomized placebo-controlled trial involving 20,536 UK patients with vascular disease or diabetes (in which a substantial reduction of cardiovascular mortality and morbidity has previously been demonstrated)."	( Effects of simvastatin 40 mg daily on muscle and liver adverse effects in a 5-year randomized placebo-controlled trial in 20,536 high-risk people. Armitage, J; Bowman, L; Collins, R; Parish, S; Tobert, J, 2009)	1.02
"These findings indicate that ezetimibe/simvastatin combination therapy is safe and effective in patients with type 2 diabetes and nonalcoholic fatty liver disease."	( [Efficacy and safety of ezetimibe/simvastatin combination therapy in patients with type 2 diabetes and nonalcoholic fatty liver disease]. Abel, T; Dinya, E; Fehér, J; Gamal Eldin, M; Kovács, A, 2009)	0.9
" The incidence of liver, muscle, and gastrointestinal-, hepatitis- and allergic reaction/rash-related adverse events were low and generally similar to those in previous studies of ezetimibe/simvastatin and/or atorvastatin."	( Lipid-altering efficacy and safety of ezetimibe/simvastatin versus atorvastatin in patients with hypercholesterolemia and the metabolic syndrome (from the VYMET study). Adewale, AJ; Ballantyne, CM; Grundy, SM; Hsueh, WA; Parving, HH; Polis, AB; Robinson, JG; Rosen, JB; Tershakovec, AM; Tomassini, JE, 2009)	0.8
" The aim of our study was to evaluate the prevalence of statin-associated adverse events in diabetic and non-diabetic patients affected by polygenic hypercholesterolemia or combined hyperlipidemia and the efficacy and tolerability of treatment with ezetimibe/simvastatin 10/10 mg/day on the same subjects experiencing the adverse events."	( Efficacy and safety of ezetimibe/simvastatin association on non-diabetic and diabetic patients with polygenic hypercholesterolemia or combined hyperlipidemia and previously intolerant to standard statin treatment. Ciccarelli, L; Cicero, AF; D'Angelo, A; Derosa, G; Franzetti, IG; Gadaleta, G; Piccinni, MN; Ragonesi, PD; Scalise, F, 2009)	0.81
" Each Centre used any of the available statins on the basis of current clinical judgement and monitored enrolled patients for adverse events during the following 2 years."	( Efficacy and safety of ezetimibe/simvastatin association on non-diabetic and diabetic patients with polygenic hypercholesterolemia or combined hyperlipidemia and previously intolerant to standard statin treatment. Ciccarelli, L; Cicero, AF; D'Angelo, A; Derosa, G; Franzetti, IG; Gadaleta, G; Piccinni, MN; Ragonesi, PD; Scalise, F, 2009)	0.63
" Patients affected by polygenic hypercholesterolemia experiencing adverse event under statin treatment obtained a significantly lower reduction than those tolerating the treatment (P < 0*001)."	( Efficacy and safety of ezetimibe/simvastatin association on non-diabetic and diabetic patients with polygenic hypercholesterolemia or combined hyperlipidemia and previously intolerant to standard statin treatment. Ciccarelli, L; Cicero, AF; D'Angelo, A; Derosa, G; Franzetti, IG; Gadaleta, G; Piccinni, MN; Ragonesi, PD; Scalise, F, 2009)	0.63
"The efficacy and adverse effect profile of the ezetimibe and simvastatin combination appear to be good for both diabetic and nondiabetic patients, and in both conditions."	( Efficacy and safety of ezetimibe/simvastatin association on non-diabetic and diabetic patients with polygenic hypercholesterolemia or combined hyperlipidemia and previously intolerant to standard statin treatment. Ciccarelli, L; Cicero, AF; D'Angelo, A; Derosa, G; Franzetti, IG; Gadaleta, G; Piccinni, MN; Ragonesi, PD; Scalise, F, 2009)	0.88
" Efficacy and safety were evaluated using lipid profiles, trough calcineurin inhibitor levels, allograft function, and adverse effects."	( The efficacy and safety of ezetimibe and low-dose simvastatin as a primary treatment for dyslipidemia in renal transplant recipients. Choi, BS; Hwang, HS; Hyoung, BJ; Jeon, YJ; Kim, YS; Lee, SY; Song, JC; Yang, CW; Yoon, HE, 2009)	0.61
" No significant change in the trough calcineurin inhibitor levels or allograft function occurred, and no serious adverse effects were observed."	( The efficacy and safety of ezetimibe and low-dose simvastatin as a primary treatment for dyslipidemia in renal transplant recipients. Choi, BS; Hwang, HS; Hyoung, BJ; Jeon, YJ; Kim, YS; Lee, SY; Song, JC; Yang, CW; Yoon, HE, 2009)	0.61
"Ezetimibe and low-dose statin treatment is safe and effective as a primary treatment for dyslipidemia in renal transplant patients."	( The efficacy and safety of ezetimibe and low-dose simvastatin as a primary treatment for dyslipidemia in renal transplant recipients. Choi, BS; Hwang, HS; Hyoung, BJ; Jeon, YJ; Kim, YS; Lee, SY; Song, JC; Yang, CW; Yoon, HE, 2009)	0.61
" We defined a composite adverse event (CAE) as discontinuation for any side effect, myalgia, or CK >3x upper limit of normal during follow-up."	( The SLCO1B1*5 genetic variant is associated with statin-induced side effects. Ali, S; Ginsburg, GS; Reed, CR; Salisbury, BA; Shah, SH; Spasojevic, I; Voora, D, 2009)	0.35
"These results showed that both the combined ezetimibe/simvastatin treatment and the simvastatin monotherapy proved to be effective and safe in patients with NAFLD and in cases of high cardiovascular risk."	( Safety and efficacy of combined ezetimibe/simvastatin treatment and simvastatin monotherapy in patients with non-alcoholic fatty liver disease. Abel, T; Dinya, E; Eldin, MG; Fehér, J; Kovács, A, 2009)	0.87
"Mean percentage changes in lipid parameters, percentages of patients achieving optimal serum lipid/apolipoprotein levels, and incidence of adverse events."	( Efficacy and safety of fenofibric acid co-administered with low- or moderate-dose statin in patients with mixed dyslipidemia and type 2 diabetes mellitus: results of a pooled subgroup analysis from three randomized, controlled, double-blind trials. Cusi, K; Davidson, MH; Jones, PH; Kelly, MT; Setze, CM; Sleep, DJ; Stolzenbach, JC; Thakker, K, 2010)	0.36
" Incidence of adverse events was generally similar among treatments."	( Efficacy and safety of fenofibric acid co-administered with low- or moderate-dose statin in patients with mixed dyslipidemia and type 2 diabetes mellitus: results of a pooled subgroup analysis from three randomized, controlled, double-blind trials. Cusi, K; Davidson, MH; Jones, PH; Kelly, MT; Setze, CM; Sleep, DJ; Stolzenbach, JC; Thakker, K, 2010)	0.36
" The primary end point, the safety of E/S plus niacin, included prespecified adverse events (ie, liver, muscle, discontinuations due to flushing, gallbladder-related, cholecystectomy, fasting glucose changes, new-onset diabetes)."	( Long-term safety and efficacy of triple combination ezetimibe/simvastatin plus extended-release niacin in patients with hyperlipidemia. Adewale, AJ; Fazio, S; Guyton, JR; Polis, AB; Ryan, NW; Tershakovec, AM; Tomassini, JE, 2010)	0.6
" Safety was evaluated based on data collected for adverse events (AEs), physical and electrocardiographic examinations, vital sign measurements, and clinical laboratory tests."	( Efficacy and safety of rosuvastatin and fenofibric acid combination therapy versus simvastatin monotherapy in patients with hypercholesterolemia and hypertriglyceridemia: a randomized, double-blind study. Carlson, DM; Gold, A; Jones, PH; Kelly, MT; McKenney, JM; Roth, EM; Setze, CM; Stolzenbach, JC; Williams, LA, 2010)	0.59
" Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established radiation injury, for example in the case of radiation accidents or acts of terrorism."	( Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity. Monceau, V; Opolon, P; Pasinetti, N; Pouzoulet, F; Schupp, C; Vozenin, MC, 2010)	0.36
" Simvastatin was more toxic than atorvastatin and the lactone form more toxic than the acid form."	( Cytotoxicity of atorvastatin and simvastatin on primary rainbow trout (Oncorhynchus mykiss) hepatocytes. Asberg, A; Ellesat, KS; Hylland, K; Thomas, KV; Tollefsen, KE, 2010)	1.55
" The FDA reissued the warning in 2008 after receiving reports of 52 cases of rhabdomyolysis in the Adverse Event Reporting System (AERS) after the label changes in 2002 and suggested use of an alternative statin for patients receiving amiodarone who require more than 20 mg simvastatin to attain lipid goals."	( Results of a safety initiative for patients on concomitant amiodarone and simvastatin therapy in a Veterans Affairs medical center. Beckey, C; Hough, A; Karimi, S; Parra, D, 2010)	0.77
"Combination E/S+N is a safe treatment option for hyperlipidaemic patients including those with DM and MetS, but requires monitoring of glucose and potentially uric acid levels."	( Long-term efficacy and safety of ezetimibe/simvastatin coadministered with extended-release niacin in hyperlipidaemic patients with diabetes or metabolic syndrome. Fazio, S; Guyton, JR; Lin, J; Shah, A; Tershakovec, AM; Tomassini, JE, 2010)	0.62
" Incidences of adverse events or creatine kinase elevations were similar between groups."	( Lipid-altering efficacy and safety profile of combination therapy with ezetimibe/statin vs. statin monotherapy in patients with and without diabetes: an analysis of pooled data from 27 clinical trials. Betteridge, DJ; Brudi, P; Farnier, M; Guyton, JR; Johnson-Levonas, AO; Leiter, LA; Lin, J; Shah, A, 2011)	0.37
" Our study enrolled 12 CAPD patients who were experiencing adverse effects from statin therapy."	( Efficacy and safety of ezetimibe and low-dose simvastatin as primary treatment for dyslipidemia in peritoneal dialysis patients. Inoue, T; Kikuta, T; Sato, T; Suzuki, H; Tsuda, M; Watanabe, Y, 2010)	0.62
" Compared to conventional markers, such as AST, ALT, and CK, the urine metabolic profile provided clearer distinction between the pre- and post-treatment groups treated with toxic levels of simvastatin."	( An effective assessment of simvastatin-induced toxicity with NMR-based metabonomics approach. Choi, MJ; Hong, SS; Hong, SW; Jung, KH; Kim, JM; Kwon, HN; Park, S; Wen, H; Yang, HJ, 2011)	0.86
" However, the side effect of flushing can challenge patient adherence to treatment."	( Niacin extended-release therapy in phase III clinical trials is associated with relatively low rates of drug discontinuation due to flushing and treatment-related adverse events: a pooled analysis. Brinton, EA; Jiang, P; Kashyap, ML; Padley, RJ; Thakkar, RB; Vo, AN, 2011)	0.37
"Data were pooled from eight NER studies (administered as NER with a maximum dosage of 1000, 1500, and 2000 mg/day, either as monotherapy or in combination with simvastatin 20 or 40 mg/day [NER/S], or lovastatin 20 or 40 mg/day [NER/L]) to evaluate rates of study discontinuation due to flushing or any treatment-related adverse events."	( Niacin extended-release therapy in phase III clinical trials is associated with relatively low rates of drug discontinuation due to flushing and treatment-related adverse events: a pooled analysis. Brinton, EA; Jiang, P; Kashyap, ML; Padley, RJ; Thakkar, RB; Vo, AN, 2011)	0.57
" Of the total number of patients treated with NER (n = 307), NER/S (n = 912), or NER/L (n = 928), 34 (11%), 105 (11%), and 127 (14%) patients discontinued due to any treatment-related adverse event, respectively, while 14 (5%), 43 (5%), and 55 (6%) discontinued due to flushing."	( Niacin extended-release therapy in phase III clinical trials is associated with relatively low rates of drug discontinuation due to flushing and treatment-related adverse events: a pooled analysis. Brinton, EA; Jiang, P; Kashyap, ML; Padley, RJ; Thakkar, RB; Vo, AN, 2011)	0.37
" SB-649868 was well tolerated at all doses in this study population, with mechanism-related adverse events (e."	( Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist. Alexander, R; Bettica, P; Gomeni, R; Nucci, G; Pyke, C; Ratti, E; Squassante, L; Zamuner, S, 2012)	0.38
" We compared isolated primary mouse skeletal muscle myocytes, C2C12 myotubes and liver HepG2 cells to detect differences that could uncover why statins are toxic in skeletal muscle but less so in the liver."	( Susceptibility to simvastatin-induced toxicity is partly determined by mitochondrial respiration and phosphorylation state of Akt. Brecht, K; Felser, A; Krähenbühl, S; Lindinger, P; Maseneni, S; Mullen, PJ; Zahno, A, 2011)	0.7
" Both monotherapy and combination therapy groups had similar incidences of all types of adverse events."	( Retrospective study on antihyperlipidemic efficacy and safety of simvastatin, ezetimibe and their combination in Korean adults. Bae, JW; Choi, CI; Jang, CG; Kim, MJ; Lee, SY; Lee, YH, 2011)	0.61
" Adverse experiences (AEs) typically associated with niacin (flushing, pruritus, increased glucose, increased uric acid) were more common with ERN/LRPT+SIMVA, and hepatic-related laboratory AEs were more common with ATORVA."	( Lipid-altering efficacy and safety profile of co-administered extended release niacin/laropiprant and simvastatin versus atorvastatin in patients with mixed hyperlipidemia. Blomqvist, P; Chen, E; Chen, F; Davidson, M; Maccubbin, D; McKenney, JM; Sirah, W; Sisk, CM; Yan, L, 2013)	0.61
" These adverse events (AEs) can have serious impact, and form a significant barrier to therapy adherence."	( A survey of the FDA's AERS database regarding muscle and tendon adverse events linked to the statin drug class. Dimbil, M; Golomb, BA; Hoffman, KB; Kraus, C, 2012)	0.38
" Safety was evaluated by monitoring adverse events, laboratory assays, vital signs, physical examinations and 12-lead electrocardiograms."	( Pharmacokinetics and safety of ezetimibe/simvastatin combination tablet: an open-label, single-dose study in healthy Chinese subjects. Chen, WL; Chu, NN; Li, XN; Xu, HR, 2012)	0.64
"Hepatocytes are used widely as a cell model for investigation of xenobiotic metabolism and the toxic mechanism of drugs."	( Integrative analysis of proteomic and transcriptomic data for identification of pathways related to simvastatin-induced hepatotoxicity. Baek, MC; Cho, YE; Kang, W; Kim, SH; Lee, HC; Lee, JE; Lee, MH; Moon, PG; Singh, TS, 2013)	0.61
" Hepatotoxicity is one of the serious adverse effects of statins, and the exact mechanism of hepatotoxicity is not yet clear."	( Mechanisms of the statins cytotoxicity in freshly isolated rat hepatocytes. Abdoli, N; Azarmi, Y; Eghbal, MA; Heidari, R, 2013)	0.39
" No serious adverse event was observed in either group."	( Efficacy and safety of morning versus evening dose of controlled-release simvastatin tablets in patients with hyperlipidemia: a randomized, double-blind, multicenter phase III trial. Cho, SW; Han, KR; Hoon Park, S; Hyun, MS; Kim, MK; Kim, SH; Kim, YK; Seo, HS, 2013)	0.62
" Their most frequent side effect is myotoxicity."	( Structural and functional characterization of simvastatin-induced myotoxicity in different skeletal muscles. Bal, IB; Onur, R; Sara, Y; Severcan, F; Simsek Ozek, N, 2014)	0.66
" Polypharmacy is a known risk factor for toxic myopathies; our data suggest that some medication combinations may simultaneously activate upstream autophagy signaling pathways while inhibiting the degradation of these newly synthesized autophagosomes, resulting in myotoxicity."	( Increased autophagy accelerates colchicine-induced muscle toxicity. Ching, JK; Ju, JS; Margeta, M; Pittman, SK; Weihl, CC, 2013)	0.39
"The NR1I3 rs2307424 genotype distribution was different between subjects with and without adverse drug reactions."	( Influence of PPARA, RXRA, NR1I2 and NR1I3 gene polymorphisms on the lipid-lowering efficacy and safety of statin therapy. Almeida, S; Bruxel, EM; Ferreira, ME; Fiegenbaum, M; Hutz, MH; Lima, LO; Pires, RC; Van der Sand, CR; Van der Sand, LC, 2013)	0.39
"Statins are potent cholesterol-lowering drugs that can have serious adverse effects on the muscles and liver."	( Efficiency of hepatocyte pretreatment with coenzyme Q10 against statin toxicity. Abdoli, N; Azarmi, Y; Eghbal, MA, 2014)	0.4
" After 8 weeks, the treatment outcomes and adverse effects of the 2 treatments were compared."	( Comparison of the efficacy and safety profile of morning administration of controlled-release simvastatin versus evening administration of immediate-release simvastatin in chronic kidney disease patients with dyslipidemia. Chung, W; Han, KH; Hwang, YH; Jo, SK; Kim, HJ; Kim, SG; Lee, CH; Oh, KH; Song, YR; Yi, YJ, 2014)	0.62
" Treatment-emergent adverse events (TEAEs) are presented as risk ratio (RR)."	( Efficacy and safety of pitavastatin versus simvastatin: a meta-analysis of randomized controlled trials. Fang, DZ; Gong, RR; Hu, MS; Jiang, Z; Lin, J; Liu, XJ; Qiu, L; Su, M; Wang, Q, 2014)	0.67
" The statins are among the most commonly prescribed drugs in medicine but have also adverse side effects and come into interactions with other drugs."	( Preliminary studies evaluating cytotoxic effect of combined treatment with methotrexate and simvastatin on green monkey kidney cells. Izdebska, M; Jagiełło-Wójtowicz, E; Natorska-Chomicka, D, )	0.35
" However, a recognized side-effect of statin therapy is myopathy, which in severe cases can present as potentially fatal rhabdomyolysis."	( Inhibition of prenyltransferase activity by statins in both liver and muscle cell lines is not causative of cytotoxicity. Gee, RH; Johnston, JD; Malia, JM; Plant, KE; Plant, NJ; Spinks, JN, 2015)	0.42
" Simvastatin was the most toxic tested compound for zebrafish embryo, followed by diclofenac."	( Toxicity screening of diclofenac, propranolol, sertraline and simvastatin using Danio rerio and Paracentrotus lividus embryo bioassays. Martins, R; Ribeiro, S; Santos, MM; Torres, T, 2015)	1.57
" They are generally well-tolerated, but myopathy is a potentially severe adverse reaction of these compounds."	( The AKT/mTOR signaling pathway plays a key role in statin-induced myotoxicity. Bonifacio, A; Bouitbir, J; Krähenbühl, S; Sanvee, GM, 2015)	0.42
" Two authors independently selected trials fulfilling these criteria: RCTs comparing Ezetimibe±statin or another lipid-lowering drug against placebo, or against the same lipid-lowering drug at the same dosage, with a follow-up at least 24 weeks and one or more of these outcomes: all-cause mortality, cardiovascular (CV) mortality, stroke, myocardial infarction (MI), cancer, serious adverse events (SAEs); we assessed the risk of bias using the Cochrane checklist."	( Clinical efficacy and safety of Ezetimibe on major cardiovascular endpoints: systematic review and meta-analysis of randomized controlled trials. Battaggia, A; Donzelli, A; Font, M; Galvano, A; Molteni, D, 2015)	0.42
"Current evidence regarding the adverse effects of fenofibrate/simvastatin combination is critically presented based on the results of large randomized controlled trials and other relevant studies."	( Safety considerations with fenofibrate/simvastatin combination. Elisaf, MS; Filippatos, TD, 2015)	0.93
"Large randomized clinical trials show that the combined administration of fenofibrate with simvastatin is not associated with significantly increased incidence of serious adverse events compared with simvastatin monotherapy."	( Safety considerations with fenofibrate/simvastatin combination. Elisaf, MS; Filippatos, TD, 2015)	0.91
" Cellular and molecular mechanisms of this adverse effect have been elusive, in particular because of the lack of in vitro models suitable for long-term exposures."	( Cytostatic Effect of Repeated Exposure to Simvastatin: A Mechanism for Chronic Myotoxicity Revealed by the Use of Mesodermal Progenitors Derived from Human Pluripotent Stem Cells. Barragan, I; Battini, JL; Cousin, C; Egesipe, AL; Giraud-Triboult, K; Ingelman-Sundberg, M; Laustriat, D; Lotteau, V; Meyniel-Schicklin, L; Peric, D; Peschanski, M; Petit, V; Pinset, C; Sitbon, M; Touhami, J, 2015)	0.68
" Hepatotoxicity is a rare but serious adverse effect of statins; however, its mechanisms are not clear."	( MicroRNAs as biomarkers of hepatotoxicity in a randomized placebo-controlled study of simvastatin and ubiquinol supplementation. Lim, SC; Lin, L; Ong, CN; Pek, SL; Sum, CF; Tavintharan, S; Woon, K, 2016)	0.66
"Epidemiological studies have shown a positive correlation between environmental particulate matter and adverse health effects."	( Particulate matter cytotoxicity in cultured SH-SY5Y cells is modulated by simvastatin: Toxicological assessment for oxidative damage. Astort, F; Ferraro, SA; Tasat, DR; Yakisich, JS, 2016)	0.67
" Statin therapy significantly lowers plasma TC and LDL levels in HIV-positive patients and is associated with low rates of adverse events."	( Comparative safety and efficacy of statins for primary prevention in human immunodeficiency virus-positive patients: a systematic review and meta-analysis. Ballocca, F; Barbero, U; Biondi-Zoccai, G; Bonora, S; Calcagno, A; Cannillo, M; Cerrato, E; D'Ascenzo, F; DiNicolantonio, JJ; Gaita, F; Gasparini, M; Gili, S; Grosso Marra, W; Lavie, CJ; Lonni, E; Mancone, M; Montefusco, A; Moretti, C; Omedè, P; Pianelli, M, 2016)	0.43
"Ezetimibe and simvastatin treatment, either as a single pill or the combined use of the individual compounds, offers limited additional risk compared with simvastatin monotherapy and comprises a safe and efficient choice for dyslipidemia treatment in high-risk and diabetic patients."	( The safety of ezetimibe and simvastatin combination for the treatment of hypercholesterolemia. Elisaf, MS; Filippatos, TD; Kei, AA, 2016)	1.09
" We aimed to quantify co-administration of MQAB with interacting drugs and associated adverse drug reactions."	( Drug safety of macrolide and quinolone antibiotics in a tertiary care hospital: administration of interacting co-medication and QT prolongation. Corti, N; Hoppe, L; Kovari, H; Maechler, S; Niedrig, D; Russmann, S, 2016)	0.43
" Electrocardiographic (ECG) monitoring and associated adverse events were validated in medical records."	( Drug safety of macrolide and quinolone antibiotics in a tertiary care hospital: administration of interacting co-medication and QT prolongation. Corti, N; Hoppe, L; Kovari, H; Maechler, S; Niedrig, D; Russmann, S, 2016)	0.43
" Forty-four MQAB users had contraindicated co-administrations of simvastatin, atorvastatin, or tizanidine and three of those related adverse drug reactions."	( Drug safety of macrolide and quinolone antibiotics in a tertiary care hospital: administration of interacting co-medication and QT prolongation. Corti, N; Hoppe, L; Kovari, H; Maechler, S; Niedrig, D; Russmann, S, 2016)	0.67
" However, adverse drug reactions were rarely found, and costs vs."	( Drug safety of macrolide and quinolone antibiotics in a tertiary care hospital: administration of interacting co-medication and QT prolongation. Corti, N; Hoppe, L; Kovari, H; Maechler, S; Niedrig, D; Russmann, S, 2016)	0.43
"SIM/SIM-mPEG micelles were found to be an effective and safe treatment for closed femoral fracture repair in mice."	( The Evaluation of Therapeutic Efficacy and Safety Profile of Simvastatin Prodrug Micelles in a Closed Fracture Mouse Model. Daluiski, A; Dusad, A; Fehringer, EV; Goldring, SR; Jia, Z; Purdue, PE; Ren, K; Wang, D; Wei, X; Yuan, H; Zhang, Y, 2016)	0.68
"Many adverse drug reactions are caused by the cytochrome P450 (CYP)-dependent activation of drugs into reactive metabolites."	( Development of a cell viability assay to assess drug metabolite structure-toxicity relationships. Jones, LH; Nadanaciva, S; Rana, P; Will, Y, 2016)	0.43
" In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment."	( Interpretation of the evidence for the efficacy and safety of statin therapy. Armitage, J; Baigent, C; Blackwell, L; Blumenthal, R; Collins, R; Danesh, J; DeMets, D; Emberson, J; Evans, S; Law, M; MacMahon, S; Martin, S; Neal, B; Peto, R; Poulter, N; Preiss, D; Reith, C; Ridker, P; Roberts, I; Rodgers, A; Sandercock, P; Schulz, K; Sever, P; Simes, J; Smeeth, L; Smith, GD; Wald, N; Yusuf, S, 2016)	0.43
" Adverse drug effects may be responsible for a fraction of nocturnal leg cramps but often go unrecognized, resulting in additional prescribing intended to deal with adverse effects that might be better addressed by reduction, substitution, or discontinuation of the offending agent."	( Quinine induced simvastatin toxicity through cytochrome inhibition - a case report. Just, JM; Just, KS; Weckbecker, K, 2016)	0.78
" Safety end points were hemorrhagic transformation, hemorrhagic events, death, infections, and serious adverse events."	( Combination of Thrombolysis and Statins in Acute Stroke Is Safe: Results of the STARS Randomized Trial (Stroke Treatment With Acute Reperfusion and Simvastatin). Bravo, Y; Bustamante, A; Cánovas, D; Corbeto, N; de Arce, A; de la Torre, J; Delgado, P; Delgado-Mederos, R; Freijo, M; García-Matas, S; Giralt, D; Jiménez, C; Lago, A; Martínez-Zabaleta, M; Masjuán, J; Moniche, F; Montaner, J; Ribó, M; Rubio, FR; Segura, T; Tejada, J; Vives-Pastor, B, 2016)	0.63
"Simvastatin plus tissue-type plasminogen activator combination seems safe in acute stroke, with low rates of bleeding complications."	( Combination of Thrombolysis and Statins in Acute Stroke Is Safe: Results of the STARS Randomized Trial (Stroke Treatment With Acute Reperfusion and Simvastatin). Bravo, Y; Bustamante, A; Cánovas, D; Corbeto, N; de Arce, A; de la Torre, J; Delgado, P; Delgado-Mederos, R; Freijo, M; García-Matas, S; Giralt, D; Jiménez, C; Lago, A; Martínez-Zabaleta, M; Masjuán, J; Moniche, F; Montaner, J; Ribó, M; Rubio, FR; Segura, T; Tejada, J; Vives-Pastor, B, 2016)	2.08
" Safety outcomes were evaluated by the risk of adverse events (AE)."	( Efficacy and safety of long-term treatment with statins for coronary heart disease: A Bayesian network meta-analysis. Bai, Y; Chan, C; Chang, X; Cheng, N; Cheng, Z; Lu, Y; Zhao, Y, 2016)	0.43
"Statins are generally well tolerated and adverse effects are relatively rare."	( Hepatotoxicity of statins and other lipid-lowering agents. Björnsson, ES, 2017)	0.46
"9 million clinical reports submitted to FDA Adverse Event Reporting System (FAERS) from 2004 to 2015."	( Effect of statins on blood pressure: Analysis on adverse events released by FDA. Ding, F; Hou, XD; Liu, XG; Wang, XK; Xie, HH; Xie, XD; Yi, K; You, T; Zhang, P, 2017)	0.46
"To our knowledge, this is the first pooled analysis on large-scale data of adverse events to identify the BP-lowering effect of statins."	( Effect of statins on blood pressure: Analysis on adverse events released by FDA. Ding, F; Hou, XD; Liu, XG; Wang, XK; Xie, HH; Xie, XD; Yi, K; You, T; Zhang, P, 2017)	0.46
" This study supports the safe use of transdermal compositions that improve on the poor bioavailability of oral berberine and have the potential to be more efficacious in the treatment of dyslipidemia or hypercholesterolemia."	( Comparative pharmacokinetics and safety assessment of transdermal berberine and dihydroberberine. Azike, CG; Baranowski, DC; Buchanan, B; Gabriele, J; Meng, Q; Poulin, MM; Zuccolo, J, 2018)	0.48
"To evaluate the onset timing of musculoskeletal adverse events (MAEs) that develop during statin monotherapy and to determine whether concomitant drugs used concurrently with statin therapy shifts the onset timing of MAEs."	( Onset timing of statin-induced musculoskeletal adverse events and concomitant drug-associated shift in onset timing of MAEs. Akimoto, H; Inoue, N; Kobayashi, D; Negishi, A; Numajiri, S; Ohshima, S; Okita, M; Oshima, S, 2018)	0.48
" The present study showed strong cytotoxic potential for the NPS 5F-PB-22 and MDAI, moderate effects for MDMA, MDPV, methylone, cathinone, 4-MEC, and mephedrone, and no toxic effects for methamphetamine."	( Cytotoxicity of new psychoactive substances and other drugs of abuse studied in human HepG2 cells using an adopted high content screening assay. Beck, A; Flockerzi, V; Maurer, HH; Meyer, MR; Richter, LHJ, 2019)	0.51
" Therefore, in T1DM, the deficiency of C-peptide may contribute to myopathy by rendering myoblast-like progenitor cells (involved in muscle regeneration) more susceptible to the toxic effects of insults such as simvastatin."	( Proinsulin C-Peptide Enhances Cell Survival and Protects against Simvastatin-Induced Myotoxicity in L6 Rat Myoblasts. Bevington, A; Brunskill, NJ; Essid, SM, 2019)	0.94
" Co-administration of MNK and SMV decreased their toxic potentials on the liver, skeletal muscles, and kidney."	( Montelukast modifies simvastatin-induced myopathy and hepatotoxicity. Ahmed, EA; Ali, MF; Hareedy, MS, 2019)	0.83
" The number of patients who stopped treatment because of adverse events was significantly higher in the simvastatin 40 mg/day plus rifaximin group (nine [56%] of 16 patients) compared with the other two groups (two [14%] of 14 for both groups; p=0·017)."	( Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trial. Abraldes, JG; Alessandria, C; Amin, A; Andrade, RJ; Angeli, P; Bernardi, M; Beuers, U; Campion, D; Caraceni, P; Carol, M; de Wit, K; Domenech, G; Durand, F; Ferrero, J; Ginès, P; Jimenez, C; Kamath, PS; Llopis, M; Mookerjee, RP; Napoleone, L; Piano, S; Pich, J; Pose, E; Roux, O; Solà, E; Torres, F; Trebicka, J; Uschner, FE; Vargas, V; Zaccherini, G, 2020)	1.05
"Treatment with simvastatin 40 mg/day plus rifaximin in patients with decompensated cirrhosis was associated with a significant increase in adverse events requiring treatment withdrawal, particularly rhabdomyolysis, compared with simvastatin 20 mg/day plus rifaximin."	( Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trial. Abraldes, JG; Alessandria, C; Amin, A; Andrade, RJ; Angeli, P; Bernardi, M; Beuers, U; Campion, D; Caraceni, P; Carol, M; de Wit, K; Domenech, G; Durand, F; Ferrero, J; Ginès, P; Jimenez, C; Kamath, PS; Llopis, M; Mookerjee, RP; Napoleone, L; Piano, S; Pich, J; Pose, E; Roux, O; Solà, E; Torres, F; Trebicka, J; Uschner, FE; Vargas, V; Zaccherini, G, 2020)	1.19
" Adverse events and changes in lipid panel profile, pulmonary function tests, and VEGF-D were assessed."	( A phase II clinical trial of the Safety Of Simvastatin (SOS) in patients with pulmonary lymphangioleiomyomatosis and with tuberous sclerosis complex. Courtwright, AM; Dorgan, D; Fleck, V; Kotloff, R; Kreider, M; Krymskaya, VP; McCormack, FX, 2020)	0.82
" The most common adverse events were peripheral edema (30%), cough (30%), and diarrhea (30%)."	( A phase II clinical trial of the Safety Of Simvastatin (SOS) in patients with pulmonary lymphangioleiomyomatosis and with tuberous sclerosis complex. Courtwright, AM; Dorgan, D; Fleck, V; Kotloff, R; Kreider, M; Krymskaya, VP; McCormack, FX, 2020)	0.82
"The combination of simvastatin with mTORi in LAM patients is safe and well-tolerated from an adverse events perspective."	( A phase II clinical trial of the Safety Of Simvastatin (SOS) in patients with pulmonary lymphangioleiomyomatosis and with tuberous sclerosis complex. Courtwright, AM; Dorgan, D; Fleck, V; Kotloff, R; Kreider, M; Krymskaya, VP; McCormack, FX, 2020)	1.15
" Myotoxicity of statins in certain individuals is often a severe side effect leading to withdrawal."	( Resveratrol for protection against statin toxicity in C2C12 and H9c2 cells. Attalah Nee Rezkallah, C; Chen, QM; Thongkum, A; Zhu, C, 2020)	0.56
"Paclitaxel-induced peripheral neuropathy (PIPN) is a common and dose-limiting adverse event."	( P-Glycoprotein Inhibition Exacerbates Paclitaxel Neurotoxicity in Neurons and Patients With Cancer. Hammer, HS; Khalaf, S; Kroetz, DL; Mortensen, C; Nielsen, F; Poetz, O; Rodriguez-Antona, C; Stage, TB; Steffensen, V; Svenningsen, ÅF; Xiong, C, 2020)	0.56
" In terms of individual toxicity, omeprazole is the most toxic of the active ingredients, followed by simvastatin, diazepam and, finally, metformin."	( Diazepam, metformin, omeprazole and simvastatin: a full discussion of individual and mixture acute toxicity. d'Auriol, M; de Souza Santos, LV; Jacob, RS; Lange, LC; Lebron, YAR; Moreira, VR, 2020)	1.05
" The study indicated that SLH formulations were safe and well-tolerated when administered to healthy males, confirming the commercial potential of SLH to enhance the bioavailability of poorly water-soluble drugs."	( A safety, tolerability, and pharmacokinetic study of a novel simvastatin silica-lipid hybrid formulation in healthy male participants. Abuhelwa, AY; Clifton, P; Joyce, P; Meola, TR; Prestidge, CA, 2021)	0.86
"3%) showed adverse events, including gastrointestinal toxicity (36."	( Safety of Chronic Simvastatin Treatment in Patients with Decompensated Cirrhosis: Many Adverse Events but No Liver Injury. Álvarez, D; Cartier, M; Marino, M; Míguez, C; Muñoz, AE; Pollarsky, F; Romero, G; Salgado, P; Vázquez, H, 2021)	0.96
"Chronic treatment with simvastatin 40 mg/day in patients with decompensated cirrhosis was associated with several adverse events, being MI the only clinically significant one, which appears to be related to the simvastatin dosage and the degree of cirrhosis severity."	( Safety of Chronic Simvastatin Treatment in Patients with Decompensated Cirrhosis: Many Adverse Events but No Liver Injury. Álvarez, D; Cartier, M; Marino, M; Míguez, C; Muñoz, AE; Pollarsky, F; Romero, G; Salgado, P; Vázquez, H, 2021)	1.27
" In conclusion, myoblasts were more susceptible to the toxic effects of simvastatin and simvastatin impaired myoblast proliferation and myotube formation."	( C2C12 myoblasts are more sensitive to the toxic effects of simvastatin than myotubes and show impaired proliferation and myotube formation. Bouitbir, J; Krähenbühl, S; Sanvee, GM, 2021)	1.1
"This study set out to optimize simvastatin (SV) in lipid nanoparticles (SLNs) to improve bioavailability, efficacy and alleviate adverse effects."	( Therapeutic advancement of simvastatin-loaded solid lipid nanoparticles (SV-SLNs) in treatment of hyperlipidemia and attenuating hepatotoxicity, myopathy and apoptosis: Comprehensive study. Abdelsalam, RM; Abo-Zalam, HB; El-Denshary, ES; Hamzawy, MA; Khalil, IA; Khattab, MM, 2021)	1.2
"There is a growing concern about the association between the combined use of daptomycin (DAP) and statins and the occurrence of musculoskeletal adverse events (MAEs), but this remains controversial."	( Association Between Statin Use and Daptomycin-related Musculoskeletal Adverse Events: A Mixed Approach Combining a Meta-analysis and a Disproportionality Analysis. Asada, M; Bando, T; Chuma, M; Goda, M; Hamano, H; Ishizawa, K; Izawa-Ishizawa, Y; Kondo, Y; Miyata, K; Nakamoto, A; Niimura, T; Okada, N; Takechi, K; Tasaki, Y; Yagi, K; Yanagawa, H; Yoshioka, T; Zamami, Y, 2022)	0.72
" Second, we conducted a disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to further confirm the results of the meta-analysis and to examine the effect of each type of statin on DAP-related MAEs in a large population."	( Association Between Statin Use and Daptomycin-related Musculoskeletal Adverse Events: A Mixed Approach Combining a Meta-analysis and a Disproportionality Analysis. Asada, M; Bando, T; Chuma, M; Goda, M; Hamano, H; Ishizawa, K; Izawa-Ishizawa, Y; Kondo, Y; Miyata, K; Nakamoto, A; Niimura, T; Okada, N; Takechi, K; Tasaki, Y; Yagi, K; Yanagawa, H; Yoshioka, T; Zamami, Y, 2022)	0.72
" Subjects diagnosed with any type of dyslipidemia (population 4804) and received pitavastatin (interventions) versus comparator (comparison) with the primary efficacy endpoint of minimization of LDL-C and non- HDL-C, had an increase in HDL-C and/or reduction in major adverse cardiac events (MACE, cardiovascular death, myocardial infarction (fatal/nonfatal), and stroke (fatal/nonfatal) and/or their composite (outcomes)."	( A Systematic Review of Randomized Clinical Trials on the Efficacy and Safety of Pitavastatin. Alkaabi, M; Amoodi, AA; Baraka, MA; Don, J; Elnour, AA; Farah, FH; Mazrouei, NA; Ramadan, A; Sadeq, A; Sam, KG, 2023)	0.91
"Drug-induced cardiotoxicity is a serious adverse effect that occurs during the administration of chemotherapeutic agents such as cyclophosphamide (CYC)."	( Simvastatin cardioprotection in cyclophosphamide-induced toxicity via the modulation of inflammasome/caspase1/interleukin1β pathway. Abdelzaher, WY; Bayoumi, AM; El-Hussieny, M; Refaie, MM; Shehata, S; Welson, NN, )	1.57

Pharmacokinetics

Pharmacokinetic and pharmacodynamic interactions between simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and diltiazem, a calcium antagonist, were investigated in 7 male and 4 female patients with hypercholesterolemia and hypertension.

Excerpt	Reference	Relevance
" We also assessed the potential pharmacokinetic interaction between simvastatin and cyclosporine by comparing mean plasma concentrations of simvastatin beta-hydroxy acid, the major metabolite of the drug, in a group of heart transplant patients treated with cyclosporine and in a control group of patients who had not received heart transplants."	( Efficacy and pharmacokinetics of simvastatin in heart transplant recipients. Campana, C; Gavazzi, A; Iacona, I; Montemartini, C; Perani, G; Raddato, V; Regazzi, MB; Viganò, M, 1995)	0.81
"The Division of Cardiology and the First Medical Clinic for the clinical study, as well as the Department of Pharmacology for the pharmacokinetic analysis."	( Efficacy and pharmacokinetics of simvastatin in heart transplant recipients. Campana, C; Gavazzi, A; Iacona, I; Montemartini, C; Perani, G; Raddato, V; Regazzi, MB; Viganò, M, 1995)	0.57
" In addition, a pharmacodynamic assay has been developed that measures HMG-CoA reductase inhibitory activity."	( Clinical pharmacokinetics and practical applications of simvastatin. Mauro, VF, 1993)	0.53
" There are no simple methods to investigate the concentration-dependent inhibition of HMG-CoA reductase in human pharmacodynamic studies."	( Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences. Fager, G; Lennernäs, H, 1997)	0.3
" Using a population pharmacokinetic approach (implemented in P-PHARM software) the ratio of dose rate to trough concentration at steady state (DR/C[SS trough]), an estimation of apparent clearance, was determined."	( Effect of simvastatin on cyclosporine unbound fraction and apparent blood clearance in heart transplant recipients. Akhlaghi, F; Brown, KF; Keogh, AM; McLachlan, AJ, 1997)	0.7
" Indeed, pharmacokinetic interactions (e."	( New insights into the pharmacodynamic and pharmacokinetic properties of statins. Baetta, R; Bellosta, S; Bernini, F; Corsini, A; Fumagalli, R; Paoletti, R, 1999)	0.3
" The values for percent 14C exhaled during the first hour (for EBT) and the pharmacokinetic parameters of midazolam (AUC, Cmax, t1/2) were not affected following multiple once-daily oral doses of simvastatin 80 mg."	( Simvastatin does not affect CYP3A activity, quantified by the erythromycin breath test and oral midazolam pharmacokinetics, in healthy male subjects. Brucker, MJ; Gagliano, K; Gillen, L; Greenberg, HE; McLoughlin, D; Prueksaritanont, T; Rogers, JD; Vega, JM; Waldman, SA; Wong, PH, 2000)	1.94
" Pharmacokinetic assessment was performed on days 14 and 28."	( Pharmacokinetic interactions between nelfinavir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and simvastatin. Hsyu, PH; Kerr, BM; Lewis, RH; Lillibridge, JH; Schultz-Smith, MD, 2001)	0.52
"Fifty-six subjects completed both pharmacokinetic study days."	( Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. Aberg, JA; Alston, B; Aweeka, F; Blaschke, T; Fang, F; Fichtenbaum, CJ; Gerber, JG; Kosel, B; Rosenkranz, SL; Segal, Y, 2002)	0.31
"The goal of this study was to develop a preliminary pharmacodynamic model for dosing of the hydroxymethylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors simvastatin and atorvastatin using neural network analysis."	( A preliminary evaluation of neural network analysis for pharmacodynamic modeling of the dosing of the hydroxymethylglutaryl coenzyme A-reductase inhibitors simvastatin and atorvastatin. Moon, A; Smith, T, 2002)	0.71
" In Study 1, there were no indications of pharmacokinetic interactions between simvastatin and ezetimibe."	( Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin. Affrime, MB; Batra, VK; Cutler, DL; Kosoglou, T; Maxwell, SE; Mellars, L; Meyer, I; Patrick, JE; Statkevich, P; Veltri, EP; Yang, B; Zhu, Y, 2002)	0.76
"To investigate in vivo the mutual pharmacokinetic interactions between bosentan and simvastatin, a CYP3A4 substrate."	( Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Dingemanse, J; Schaarschmidt, D; van Giersbergen, PL, 2003)	0.75
" The pharmacokinetic parameters of bosentan and its metabolites were not influenced by concomitant treatment with simvastatin: areas under the plasma concentration-time curve over one administration interval of 12 hours (AUC(tau)) [geometric mean and 95% CI] were 4586 (3719-5656) and 4928 (3945-6156) micro g * h/L."	( Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Dingemanse, J; Schaarschmidt, D; van Giersbergen, PL, 2003)	0.74
" Treatments were compared for the pharmacokinetic parameters AUC0-infinity, Cmax, tmax, and t 1/2 of highly lipophilic drugs and active metabolites."	( Effects of orlistat, a lipase inhibitor, on the pharmacokinetics of three highly lipophilic drugs (amiodarone, fluoxetine, and simvastatin) in healthy volunteers. Kanitra, L; Moore, R; Mulligan, TE; Zhi, J, 2003)	0.52
" The pharmacokinetic parameters AUC(0-t), AUC(0-variant), C(MAX), T(MAX), T(1/2) and elimination rate constant were determined from plasma concentration-time profile for both formulations and were compared statistically to evaluate bioequivalence between the two brands, using the statistical modules recommended by FDA."	( Pharmacokinetics and bioequivalence evaluation of two simvastatin 40 mg tablets (Simvast and Zocor) in healthy human volunteers. Adel, A; Admour, I; Alam, SM; Astigarraga, RE; Dham, R; Idkaidek, N; Najib, NM; Nucci, GD, 2003)	0.57
" Compared to administration of repaglinide alone, concomitant ketoconazole increased mean AUC0-infinity for repaglinide by 15% and mean Cmax by 7%."	( Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide. Hansen, KT; Hatorp, V; Thomsen, MS, 2003)	0.32
" Two additional blood samples were taken for imatinib pharmacokinetic (PK) assessment on day 8 before, and 24 h after, imatinib administration."	( Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia. Beck, J; Bond, E; Capdeville, R; Dutreix, C; Fischer, T; Huber, C; Mehring, G; Meinhardt, P; Milosavljev, S; O'Brien, SG; Peng, B, 2003)	0.55
" A 2-period, randomized, open-label, crossover study was conducted in 12 subjects to determine if fenofibrate and simvastatin are subject to a clinically relevant pharmacokinetic interaction at steady state."	( Simvastatin does not have a clinically significant pharmacokinetic interaction with fenofibrate in humans. Bergman, AJ; Burke, J; Hartford, A; He, W; Lasseter, KC; Liu, L; Murphy, G; Paolini, JF; Prueksaritanont, T; Qiu, Y; Valesky, R; Vega, JM; Zhao, JJ, 2004)	1.98
" Studies compared the multiple-dose pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with 4 inhibitors of cytochrome P450-3A4 isoenzymes in healthy subjects."	( Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors. Jacobson, TA, 2004)	0.78
"Pharmacokinetic and pharmacodynamic interactions between simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and diltiazem, a calcium antagonist, were investigated in 7 male and 4 female patients with hypercholesterolemia and hypertension."	( Pharmacokinetic and pharmacodynamic interactions between simvastatin and diltiazem in patients with hypercholesterolemia and hypertension. Hayashi, H; Ishizaki, T; Kosuge, K; Nishio, S; Ohashi, K; Satoh, H; Uchida, S; Watanabe, H; Yamada, H, 2004)	0.81
"Statins (HMG-CoA reductase inhibitors) are one of the most widely prescribed classes of drugs throughout the world, because of their excellent cholesterol-lowering effect and overall safety profile except for rare but fatal rhabdomyolysis arising either directly or indirectly by pharmacokinetic interactions with certain other drugs."	( A literature search on pharmacokinetic drug interactions of statins and analysis of how such interactions are reflected in package inserts in Japan. Hasegawa, R; Hirata-Koizumi, M; Miyake, S; Saito, M; Urano, T, 2005)	0.33
"A MEDLINE search from 1996 to June 2004 was carried out to identify studies on clinical pharmacokinetic drug interactions for the five statins."	( A literature search on pharmacokinetic drug interactions of statins and analysis of how such interactions are reflected in package inserts in Japan. Hasegawa, R; Hirata-Koizumi, M; Miyake, S; Saito, M; Urano, T, 2005)	0.33
"All pharmacokinetic drug interactions including relevant quantitative data for potential effectors and details on mechanisms of interaction need to be given in package inserts as soon as the information becomes available, to ensure safe and proper use of the drugs concerned."	( A literature search on pharmacokinetic drug interactions of statins and analysis of how such interactions are reflected in package inserts in Japan. Hasegawa, R; Hirata-Koizumi, M; Miyake, S; Saito, M; Urano, T, 2005)	0.33
" The serum concentration of cerivastatin showed that the half-life of cerivastatin in this patient was 22."	( Clearance rates of cerivastatin metabolites in a patient with cerivastatin-induced rhabdomyolysis. Ishii, T; Ishikawa, CT; Miyashita, Y; Murano, T; Ozaki, H; Shirai, K; Toyoda, A, 2005)	0.33
"To characterize the pharmacokinetics of simvastatin (SV) and simvastatin acid (SVA), a lactone-acid pair known to undergo reversible metabolism, and to better understand mechanisms underlying pharmacokinetic interactions observed between SV and gemfibrozil."	( Interconversion pharmacokinetics of simvastatin and its hydroxy acid in dogs: effects of gemfibrozil. Brunner, J; Lin, JH; Michel, K; Mu, L; Prueksaritanont, T; Qiu, Y; Richards, KM, 2005)	0.87
" Blood samples for pharmacokinetic analysis were obtained immediately before and up to 72 hours after administration during each of the 4 treatment periods."	( An open-label, crossover study of the pharmacokinetics of Insoluble Drug Delivery-MicroParticle fenofibrate in combination with atorvastatin, simvastatin, and extended-release niacin in healthy volunteers. Braun, SL; Guha-Ray, DK; Penn, R; Rains, KT; Sawyers, WG; Williams, RX, 2006)	0.54
" However, other pharmacokinetic parameters including peak plasma concentrations and half-life did not show any difference between genotype groups."	( Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects. Kang, DK; Kim, KA; Lee, OJ; Park, JY; Park, PW, 2007)	0.58
"The potential for a pharmacokinetic drug interaction between valsartan, an antihypertensive drug, and simvastatin, a lipid-lowering agent, was investigated in this study."	( Evaluation of a pharmacokinetic interaction between valsartan and simvastatin in healthy subjects. Humbert, H; Pommier, F; Prasad, P; Reynolds, CV; Sunkara, G; Yeh, C, 2007)	0.79
" There fore, this study was conducted to determine the potential for pharmacokinetic drug-drug interaction between vildagliptin and simvastatin at steady-state."	( Evaluation of the potential for steady-state pharmacokinetic interaction between vildagliptin and simvastatin in healthy subjects. Ayalasomayajula, SP; Campestrini, J; Dole, K; He, YL; Humbert, H; Ligueros-Saylan, M; Sunkara, G; Wang, Y, 2007)	0.76
" Pharmacokinetic and statistical analyses were performed using WinNonlin and SAS, respectively."	( Evaluation of the potential for steady-state pharmacokinetic interaction between vildagliptin and simvastatin in healthy subjects. Ayalasomayajula, SP; Campestrini, J; Dole, K; He, YL; Humbert, H; Ligueros-Saylan, M; Sunkara, G; Wang, Y, 2007)	0.56
" The aim of this study was to characterize the pharmacokinetic interactions of mipomersen sodium with simvastatin and ezetimibe."	( Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2'-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe. Flaim, JD; Geary, RS; Riley, GC; Tribble, DL; vanVliet, AA; Wedel, MK; Yu, RZ, 2009)	0.76
" Mipomersen sodium pharmacokinetic profiles were assessed following the first dose (mipomersen sodium alone) and the last dose (mipomersen sodium in combination with simvastatin or ezetimibe)."	( Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2'-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe. Flaim, JD; Geary, RS; Riley, GC; Tribble, DL; vanVliet, AA; Wedel, MK; Yu, RZ, 2009)	0.74
"The area under the plasma concentration-time curve (AUC) from 0 to 24 hours (AUC(24)), maximum plasma concentration and apparent elimination half-life values of mipomersen sodium were similar when administered alone and in combination with oral simvastatin or oral ezetimibe."	( Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2'-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe. Flaim, JD; Geary, RS; Riley, GC; Tribble, DL; vanVliet, AA; Wedel, MK; Yu, RZ, 2009)	0.73
"These data provide evidence that mipomersen sodium exhibits no clinically relevant pharmacokinetic interactions with the disposition and clearance of simvastatin or ezetimibe, and vice versa."	( Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2'-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe. Flaim, JD; Geary, RS; Riley, GC; Tribble, DL; vanVliet, AA; Wedel, MK; Yu, RZ, 2009)	0.74
"ABCB1 haplotypes were determined in 534 healthy Finnish volunteers, of whom 24 participated in a pharmacokinetic study on simvastatin and atorvastatin."	( ABCB1 haplotypes differentially affect the pharmacokinetics of the acid and lactone forms of simvastatin and atorvastatin. Keskitalo, JE; Kurkinen, KJ; Neuvoneni, PJ; Niemi, M, 2008)	0.77
" This novel method has been applied to human pharmacokinetic study."	( Development and validation of a highly sensitive and robust LC-ESI-MS/MS method for simultaneous quantitation of simvastatin acid, amlodipine and valsartan in human plasma: application to a clinical pharmacokinetic study. Mullangi, R; Ramani, AV; Sengupta, P, 2009)	0.56
" Both juices did not have a significant effect on the pharmacokinetic parameters of either simvastatin lactone (SVL) or its active metabolite simvastatin hydroxy acid (SVA) when administered concomitantly in a dose of 20 mg/kg over 28 days."	( Toxicological and Pharmacokinetic Evaluation of Concomitant Intake of Grapefruit Juice and Simvastatin in Rats after Repeated Treatment over 28 Days. Butterweck, V; Derendorf, H; Frye, R; Galloway, C; Zdrojewski, I, 2009)	0.79
" Because of the likely use of anacetrapib with hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, we aimed to evaluate the potential for a pharmacokinetic interaction with simvastatin."	( Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Bieberdorf, FA; Chodakewitz, J; Garg, A; Jin, B; Keshavarz, SS; Krishna, R; Wagner, JA, 2009)	0.78
"There appears to be no clinically meaningful effect of anacetrapib on the pharmacokinetic parameters of simvastatin."	( Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Bieberdorf, FA; Chodakewitz, J; Garg, A; Jin, B; Keshavarz, SS; Krishna, R; Wagner, JA, 2009)	0.8
" The pharmacokinetic parameters of verapamil and norverapamil in rats were determined after the oral administration of verapamil (9 mg/kg) in the presence or absence of simvastatin (0."	( Effects of simvastatin on the pharmacokinetics of verapamil and its main metabolite, norverapamil, in rats. Choi, DH; Choi, JS; Li, C, )	0.72
" Pharmacokinetic parameters were determined for both simvastatin (the inactive prodrug) and simvastatin acid (the active moiety)."	( Pharmacokinetic comparison of controlled-release and immediate-release oral formulations of simvastatin in healthy Korean subjects: a randomized, open-label, parallel-group, single- and multiple-dose study. Jang, SB; Kim, KH; Kim, YI; Kwon, BJ; Lee, YJ; Lim, LA; Park, K; Park, KM; Park, MS; Woo, JS, 2010)	0.83
"To explore if non-concurrent amlodipine dosing results in less drug interaction, the pharmacokinetic profiles, safety and efficacy endpoints were assessed following repeated doses of simvastatin, co-administered concurrently or non-concurrently with amlodipine in patients with coexisting hypertension and hyperlipidemia."	( Non-concurrent dosing attenuates the pharmacokinetic interaction between amlodipine and simvastatin. Choi, JW; Kim, SH; Lee, H; Lee, SJ; Lim, HE; Park, CG, 2010)	0.77
"The Cmax and AUClast and of simvastatin acid in the non-concurrent amlodipine dosing group were 63."	( Non-concurrent dosing attenuates the pharmacokinetic interaction between amlodipine and simvastatin. Choi, JW; Kim, SH; Lee, H; Lee, SJ; Lim, HE; Park, CG, 2010)	0.88
"This was an open-label, randomized, three-period, multiple-dose crossover study that assessed the potential for pharmacokinetic interaction between extended-release niacin and ezetimibe/simvastatin and their major metabolites."	( Assessment of potential pharmacokinetic interactions of ezetimibe/simvastatin and extended-release niacin tablets in healthy subjects. Cutler, DL; Kim, KT; Kosoglou, T; Statkevich, P; Taggart, W; Triantafyllou, I; Xuan, F; Zhu, Y, 2011)	0.8
"There is a small pharmacokinetic drug interaction between ER niacin and ezetimibe/simvastatin and although this is not considered to be clinically significant, the concomitant use of these drugs should be appropriately monitored, especially during the niacin titration period."	( Assessment of potential pharmacokinetic interactions of ezetimibe/simvastatin and extended-release niacin tablets in healthy subjects. Cutler, DL; Kim, KT; Kosoglou, T; Statkevich, P; Taggart, W; Triantafyllou, I; Xuan, F; Zhu, Y, 2011)	0.83
" Pharmacokinetic parameters of losartan and EXP-3174 in rats were determined after oral and intravenous administration of losartan (9 mg/kg) without and with HMG-CoA reductase inhibitors (1 mg/kg)."	( Effects of HMG-CoA reductase inhibitors on the pharmacokinetics of losartan and its main metabolite EXP-3174 in rats: possible role of CYP3A4 and P-gp inhibition by HMG-CoA reductase inhibitors. Choi, DH; Choi, JS; Yang, SH, 2011)	0.37
" Pharmacokinetic results suggest that simvastatin is not likely to compromise the activity of anastrozole."	( Effect of simvastatin on the pharmacokinetics of anastrozole. Bao, T; Blackford, AL; Stearns, V, 2012)	1.05
" The aim of these studies was to assess the potential for pharmacokinetic interaction between dapagliflozin, a sodium glucose co-transporter-2 inhibitor being developed for the treatment of T2DM, and four medications commonly prescribed in patients with T2DM and cardiovascular disease: simvastatin, valsartan, warfarin, and digoxin."	( Lack of pharmacokinetic interactions between dapagliflozin and simvastatin, valsartan, warfarin, or digoxin. Boulton, DW; Chang, M; Griffen, SC; Kasichayanula, S; LaCreta, FP; Liu, X; Shyu, WC, 2012)	0.79
"Potential pharmacokinetic interactions between 20 mg dapagliflozin, 40 mg simvastatin, or 320 mg valsartan were assessed in an open-label, randomized, five-period, five-treatment, unbalanced crossover study in 24 healthy subjects."	( Lack of pharmacokinetic interactions between dapagliflozin and simvastatin, valsartan, warfarin, or digoxin. Boulton, DW; Chang, M; Griffen, SC; Kasichayanula, S; LaCreta, FP; Liu, X; Shyu, WC, 2012)	0.85
" The pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined after oral and intravenous administration of diltiazem to rats in the presence and absence of simvastatin (0."	( Effects of simvastatin on the pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, after oral and intravenous administration in rats: possible role of P-glycoprotein and CYP3A4 inhibition by simvastatin. Choi, DH; Choi, JS; Li, C, 2011)	0.95
" The developed assay was successfully applied to a pharmacokinetic study in human volunteers."	( Simultaneous determination of sitagliptin and simvastatin in human plasma by LC-MS/MS and its application to a human pharmacokinetic study. Burugula, L; Kandhagatla, R; Lodagala, DS; Makula, A; Mullangi, R; Pilli, NR, 2013)	0.65
"In the absence of clinical studies, the ability to project the direction and the magnitude of changes in bioavailability of drug therapy, using evidence-based mechanistic pharmacokinetic in silico models would be of significant value in guiding prescribers to make the necessary adjustments to dosage regimens for an increasing population of patients who are undergoing bariatric surgery."	( A mechanistic pharmacokinetic model to assess modified oral drug bioavailability post bariatric surgery in morbidly obese patients: interplay between CYP3A gut wall metabolism, permeability and dissolution. Ammori, BJ; Ashcroft, DM; Darwich, AS; Jamei, M; Pade, D; Rostami-Hodjegan, A, 2012)	0.38
"4) in the maximum plasma concentration (C(max)), area under the concentration-time curve from time 0 to infinity (AUC(0-∞)), and terminal half-life (t(1/2)), respectively, of midazolam; the time to peak plasma concentration (t(max)) was unchanged."	( Pharmacokinetic interactions of almorexant with midazolam and simvastatin, two CYP3A4 model substrates, in healthy male subjects. Alessi, F; Dingemanse, J; Hoch, M; Hoever, P; Theodor, R, 2013)	0.63
" The pharmacokinetic parameters for ezetimibe and simvastatin were assessed by determining total ezetimibe, free ezetimibe, simvastatin and simvastatin acid concentrations using a validated liquid chromatography-tandem mass spectrometry method."	( Pharmacokinetics and safety of ezetimibe/simvastatin combination tablet: an open-label, single-dose study in healthy Chinese subjects. Chen, WL; Chu, NN; Li, XN; Xu, HR, 2012)	0.9
"The pharmacokinetic parameters (mean ± SD) for total ezetimibe and free ezetimibe following a single dose were: maximum plasma drug concentration (C(max)) 81."	( Pharmacokinetics and safety of ezetimibe/simvastatin combination tablet: an open-label, single-dose study in healthy Chinese subjects. Chen, WL; Chu, NN; Li, XN; Xu, HR, 2012)	0.64
" GBE administration reduced mean simvastatin area under the curve (AUC)0-24, AUC0-∞ and Cmax by 39% (p = 0."	( Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and Ginkgo biloba extracts in healthy subjects. Chen, Y; Dai, LL; Fan, L; Peng, XD; Shen, MX; Tan, ZR; Wu, HZ; Yang, GP; Zhou, HH, 2013)	0.9
"A pharmacokinetic study of simvastatin (single oral dose, 40 mg) was conducted in 17 healthy Chinese volunteers."	( Simvastatin pharmacokinetics in healthy Chinese subjects and its relations with CYP2C9, CYP3A5, ABCB1, ABCG2 and SLCO1B1 polymorphisms. Jiang, B; Ruan, ZR; Yuan, H; Zeng, S; Zhou, Q, 2013)	2.13
" A physiologically based pharmacokinetic model was used to quantitatively predict the impact of interleukin-6 (IL-6) on sensitive CYP3A4 substrates."	( A physiologically based pharmacokinetic modeling approach to predict disease-drug interactions: suppression of CYP3A by IL-6. Almond, LM; Gardner, I; Jamei, M; Joshi, A; Kenny, JR; Machavaram, KK; Rostami-Hodjegan, A; Tay, S; Wong, S, 2013)	0.39
" In a pharmacodynamic study, the percent increase in cholesterol was less with PAMAM dendrimer formulations as compared to pure drug."	( Pharmacokinetic and pharmacodynamic studies of poly(amidoamine) dendrimer based simvastatin oral formulations for the treatment of hypercholesterolemia. Chauhan, AS; Kulhari, DP; Kulhari, H; Prajapati, SK, 2013)	0.62
" The analysis of variance (ANOVA) was used to test for differences between Test (SMV under co-administration with ESL) and Reference (SMV administered alone) treatments for AUC0-∞, AUC0-t and Cmax of SMV and SMV-acid."	( Effect of repeated administration of eslicarbazepine acetate on the pharmacokinetics of simvastatin in healthy subjects. Falcão, A; Nunes, T; Pinto, R; Soares-da-Silva, P, 2013)	0.61
" A semi-physiologically based pharmacokinetic model (semi-PBPK) characterizing mechanism-based auto-inhibition was developed to predict the stereoselective pharmacokinetic profiles of verapamil and norverapamil following single or multiple oral doses."	( A semi-physiologically-based pharmacokinetic model characterizing mechanism-based auto-inhibition to predict stereoselective pharmacokinetics of verapamil and its metabolite norverapamil in human. Liu, L; Liu, X; Sai, Y; Wang, D; Wang, J; Xia, S; Xue, W, 2013)	0.39
" In conclusion, this study has quantitatively described the pharmacokinetic interaction between simvastatin and amlodipine using a modeling approach."	( Development of a pharmacokinetic interaction model for co-administration of simvastatin and amlodipine. Jang, SB; Lee, D; Lim, LA; Park, K; Roh, H; Son, H, 2014)	0.85
" The final population pharmacokinetic model shows that the elimination rate constant for simvastatin acid, the active form by hydrolysis of its lactone prodrug (i."	( Genetic algorithm guided population pharmacokinetic model development for simvastatin, concurrently or non-concurrently co-administered with amlodipine. Chaturvedula, A; Lee, H; Sale, ME, 2014)	0.86
" Pharmacokinetic parameters on days 1 and 7 were compared."	( Pharmacokinetics of niacin, simvastatin and their metabolites in healthy Chinese subjects after single and multiple doses of a fixed dose combination tablet of niacin extended release/simvastatin. Han, J; Liu, HC; Liu, M; Wang, XL; Wang, ZL; Yang, M; Zhang, D; Zhang, YN, 2014)	0.7
"Although organic anion transporting polypeptide (OATP)-mediated hepatic uptake is generally conserved between rodents and humans at a gross pharmacokinetic level, the presence of three major hepatic OATPs with broad overlap in substrate and inhibitor affinity, and absence of rodent-human orthologs preclude clinical translation of single-gene knockout/knockin findings."	( Utility of Oatp1a/1b-knockout and OATP1B1/3-humanized mice in the study of OATP-mediated pharmacokinetics and tissue distribution: case studies with pravastatin, atorvastatin, simvastatin, and carboxydichlorofluorescein. Bao, JQ; Fallon, JK; Higgins, JW; Ke, AB; Manro, JR; Smith, PC; Zamek-Gliszczynski, MJ, 2014)	0.6
"There were no significant associations between the pharmacokinetic parameters of simvastatin lactone and gender."	( Pharmacokinetics of simvastatin lactone and its active metabolite simvastatin hydroxy acid in healthy Chinese male and female volunteers. Cai, Y; Huang, J; Ren, X; Song, Y; Wang, X; Xu, H; Yang, W; Zhang, LR; Zhang, S; Zhang, T; Zhao, D; Zuo, M, 2014)	0.95
" Plasma concentrations of simvastatin and simvastatin acid were measured in 2,182 and 2,130 samples, respectively, and the pharmacokinetic data were analyzed using NONMEM."	( Population pharmacokinetic analysis of simvastatin and its active metabolite with the characterization of atypical complex absorption kinetics. Bae, KS; Cho, SH; Choe, S; Ghim, JL; Jin, SJ; Jung, JA; Kim, HS; Kim, U; Lim, HS; Noh, YH; Park, HJ, 2014)	0.97
" Pharmacokinetic modeling preferred the inter-conversion between simvastatin and simvastatin acid."	( Population pharmacokinetic analysis of simvastatin and its active metabolite with the characterization of atypical complex absorption kinetics. Bae, KS; Cho, SH; Choe, S; Ghim, JL; Jin, SJ; Jung, JA; Kim, HS; Kim, U; Lim, HS; Noh, YH; Park, HJ, 2014)	0.91
"A pharmacokinetic model describing the complex, multiple peak, absorption kinetics of simvastatin was formulated using three parallel, mixed zero and first-order absorptions."	( Population pharmacokinetic analysis of simvastatin and its active metabolite with the characterization of atypical complex absorption kinetics. Bae, KS; Cho, SH; Choe, S; Ghim, JL; Jin, SJ; Jung, JA; Kim, HS; Kim, U; Lim, HS; Noh, YH; Park, HJ, 2014)	0.9
"The aim of this work was to develop a joint population pharmacokinetic model for simvastatin (SV) and its active metabolite, simvastatin acid (SVA), that incorporates the effects of multiple genetic polymorphisms and clinical/demographic characteristics."	( Identification of the effect of multiple polymorphisms on the pharmacokinetics of simvastatin and simvastatin acid using a population-modeling approach. Aarons, L; Dickinson, G; Galetin, A; Guo, Y; Hall, S; Rostami-Hodjegan, A; Tsamandouras, N, 2014)	0.85
" The findings imply that the observed pharmacokinetic interaction is unlikely clinically relevant, and support the combined use of simvastatin and fenofibrate not only given at staggered interval but also given simultaneously."	( Pharmacokinetic interaction between simvastatin and fenofibrate with staggered and simultaneous dosing: Does it matter? Ansquer, JC; Aubonnet, P; Beckmann, K; Driessen, S; Lehnick, D; Mihara, K; Olbrich, M; Piskol, G; van Amsterdam, P; van Assche, H; Winsemius, A, 2014)	0.88
" Three separate open-label, randomized, crossover studies evaluated the potential for pharmacokinetic interaction between extended-release niacin (with and without concomitant laropiprant) and simvastatin in healthy subjects."	( Effects of Extended-Release Niacin and Extended-Release Niacin/Laropiprant on the Pharmacokinetics of Simvastatin in Healthy Subjects. Crumley, T; De Kam, PJ; Dishy, V; Lai, E; Lauring, B; Liu, F; Sisk, C; Wagner, J; Wenning, L, )	0.54
"No relevant drug-drug interaction was observed, and pharmacokinetic results suggest that no dose adjustments for either drug are necessary when empagliflozin and simvastatin are co-administered."	( Pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, and simvastatin following co-administration in healthy volunteers. Broedl, UC; Lang, B; Macha, S; Pinnetti, S, 2014)	0.82
"To develop a population physiologically-based pharmacokinetic (PBPK) model for simvastatin (SV) and its active metabolite, simvastatin acid (SVA), that allows extrapolation and prediction of their concentration profiles in liver (efficacy) and muscle (toxicity)."	( Development and Application of a Mechanistic Pharmacokinetic Model for Simvastatin and its Active Metabolite Simvastatin Acid Using an Integrated Population PBPK Approach. Aarons, L; Dickinson, G; Galetin, A; Guo, Y; Hall, S; Rostami-Hodjegan, A; Tsamandouras, N, 2015)	0.88
" At present, pharmacokinetic data of the interaction between both drugs are available."	( A pharmacokinetic drug-drug interaction model of simvastatin and clarithromycin in humans. Chaiwong, K; Lohitnavy, M; Methaneethorn, J; Pongpanich, K; Sonsingh, P, 2014)	0.66
"Selected pharmacokinetic interaction study was obtained from PubMed search."	( A pharmacokinetic drug-drug interaction model of simvastatin and clarithromycin in humans. Chaiwong, K; Lohitnavy, M; Methaneethorn, J; Pongpanich, K; Sonsingh, P, 2014)	0.66
" Even though, pharmacokinetic data regarding the interaction between both drugs have been published, their use is limited to semiquantitative applications."	( A pharmacokinetic drug-drug interaction model of simvastatin and verapamil in humans. Chamnansua, M; Kaewdang, N; Lohitnavy, M; Methaneethorn, J, 2014)	0.66
"Eligible pharmacokinetic interaction study between simvastatin and verapamil in humans was selected from PubMed database."	( A pharmacokinetic drug-drug interaction model of simvastatin and verapamil in humans. Chamnansua, M; Kaewdang, N; Lohitnavy, M; Methaneethorn, J, 2014)	0.91
" The final model adequately describes pharmacokinetic interaction between simvastatin and verapamil which can be helpful in prediction of rhabdomyolysis in patients with concurrent use of these drugs."	( A pharmacokinetic drug-drug interaction model of simvastatin and verapamil in humans. Chamnansua, M; Kaewdang, N; Lohitnavy, M; Methaneethorn, J, 2014)	0.89
"Eligible pharmacokinetic studies were selected from Pubmed database and concentration time course data were digitally extracted and used for model development."	( Pharmacokinetic modeling of simvastatin, nelfinavir and their interaction in humans. Jindasri, W; Kraiboot, A; Kunyamee, P; Lohitnavy, M; Methaneethorn, J; Wattanasaovaluk, W, 2014)	0.7
"Three compartmental pharmacokinetic models were successfully developed."	( Pharmacokinetic modeling of simvastatin, nelfinavir and their interaction in humans. Jindasri, W; Kraiboot, A; Kunyamee, P; Lohitnavy, M; Methaneethorn, J; Wattanasaovaluk, W, 2014)	0.7
"Simvastatin-nelfinavir pharmacokinetic interaction can be explained by our final model."	( Pharmacokinetic modeling of simvastatin, nelfinavir and their interaction in humans. Jindasri, W; Kraiboot, A; Kunyamee, P; Lohitnavy, M; Methaneethorn, J; Wattanasaovaluk, W, 2014)	2.14
"Volume of distribution is one of the most important pharmacokinetic properties of a drug candidate."	( Volume of Distribution in Drug Design. Beaumont, K; Di, L; Maurer, TS; Smith, DA, 2015)	0.42
" An open-label, randomized, 5-period crossover study in healthy Chinese was designed to evaluate the pharmacokinetic interaction and tolerability of multiple doses of certain TCMs on a single dose of simvastatin."	( Effects of four traditional Chinese medicines on the pharmacokinetics of simvastatin. Hu, P; Jiang, J; Zhao, Q, 2015)	0.84
" Clopidogrel 75 mg (day 3) had no significant effect on the pharmacokinetic variables of simvastatin or simvastatin acid compared with placebo."	( Clopidogrel Has No Clinically Meaningful Effect on the Pharmacokinetics of the Organic Anion Transporting Polypeptide 1B1 and Cytochrome P450 3A4 Substrate Simvastatin. Backman, JT; Itkonen, MK; Neuvonen, M; Neuvonen, PJ; Niemi, M; Tornio, A, 2015)	0.84
" ratio of simvastatin acid to simvastatin), whereas the SLCO1B1 rs4149056 and CYP2D6*5 variants were related to a higher Cmax ratio."	( Impact of CYP2D6, CYP3A5, CYP2C19, CYP2A6, SLCO1B1, ABCB1, and ABCG2 gene polymorphisms on the pharmacokinetics of simvastatin and simvastatin acid. Bae, KS; Cho, SH; Choe, S; Choi, HY; Ghim, JL; Jin, SJ; Jung, JA; Kim, HS; Lim, HS, 2015)	1.03
"To evaluate the potential pharmacokinetic (PK) and pharmacodynamic (PD, glucose-lowering effect) interaction between simvastatin and piragliatin, both CYP3A substrates, 30 patients with type 2 diabetes mellitus participated in this open-label, randomized, 6-sequence, 3-way crossover (William's design) study."	( Lack of Potential Pharmacokinetic and Pharmacodynamic Interactions Between Piragliatin, a Glucokinase Activator, and Simvastatin in Patients With Type 2 Diabetes Mellitus. Boldrin, M; Georgy, A; Liang, Z; Zhai, S; Zhi, J, 2016)	0.85
" The proposed method was applied to the drug-drug pharmacokinetic interaction study of SV combined with BBR after oral administration in rats."	( Validated UPLC-MS/MS method for simultaneous determination of simvastatin, simvastatin hydroxy acid and berberine in rat plasma: Application to the drug-drug pharmacokinetic interaction study of simvastatin combined with berberine after oral administratio Li, G; Liu, M; Su, X; Zhao, G; Zhao, L, 2015)	0.66
" Even though pharmacokinetic data regarding such interaction are available, they cannot be used for quantitative prediction."	( Pharmacokinetic model for the inhibition of simvastatin metabolism by itraconazole. Chan-Im, D; Chiang-Ngernthanyakool, R; Lohitnavy, M; Methaneethorn, J; Phaohorm, S; Tongpeng, W, 2015)	0.68
"Published data involving pharmacokinetic of simvastatin, itraconazole, and pharmacokinetic interaction between simvastatin and itraconazole were selected from PubMed search."	( Pharmacokinetic model for the inhibition of simvastatin metabolism by itraconazole. Chan-Im, D; Chiang-Ngernthanyakool, R; Lohitnavy, M; Methaneethorn, J; Phaohorm, S; Tongpeng, W, 2015)	0.94
" The present studies assessed the potential for pharmacokinetic interaction between fostamatinib and the commonly prescribed medications oral contraceptive (OC), warfarin, and statins (rosuvastatin, simvastatin) in healthy subjects."	( Effects of Fostamatinib on the Pharmacokinetics of Oral Contraceptive, Warfarin, and the Statins Rosuvastatin and Simvastatin: Results From Phase I Clinical Studies. Brealey, C; Elsby, R; Gillen, M; Holmes, V; Martin, P; Mathews, D; Oliver, S; Ritter, J; Severin, P; Surry, D, 2016)	0.83
" Fostamatinib increased rosuvastatin AUC by 96% (CI 78-115) and Cmax by 88% (CI 69-110), and increased simvastatin acid AUC by 74% (CI 50-102) and Cmax by 83% (CI 57-113)."	( Effects of Fostamatinib on the Pharmacokinetics of Oral Contraceptive, Warfarin, and the Statins Rosuvastatin and Simvastatin: Results From Phase I Clinical Studies. Brealey, C; Elsby, R; Gillen, M; Holmes, V; Martin, P; Mathews, D; Oliver, S; Ritter, J; Severin, P; Surry, D, 2016)	0.86
"To examine whether strict control of clinical trial conditions could reduce apparent differences of pharmacokinetic (PK) parameters among ethnic groups."	( Absence of ethnic differences in the pharmacokinetics of moxifloxacin, simvastatin, and meloxicam among three East Asian populations and Caucasians. Hasunuma, T; Jang, IJ; Kaneko, M; Kaniwa, N; Kawai, S; Saito, Y; Takeuchi, M; Tohkin, M; Uyama, Y; Watanabe, H; Yamazoe, Y; Yimin, C, 2016)	0.67
" Cmax values of moxifloxacin and simvastatin, but not meloxicam, showed significant differences."	( Absence of ethnic differences in the pharmacokinetics of moxifloxacin, simvastatin, and meloxicam among three East Asian populations and Caucasians. Hasunuma, T; Jang, IJ; Kaneko, M; Kaniwa, N; Kawai, S; Saito, Y; Takeuchi, M; Tohkin, M; Uyama, Y; Watanabe, H; Yamazoe, Y; Yimin, C, 2016)	0.95
"To investigate the effect of Shexiang Baoxin Pill (SBP), a tranditional Chinese medicine, on the pharmacokinetic (PK) parameters of simvastatin in healthy volunteers' plasma, a quantitative method was developed using an Agilent G6410A rapid performance liquid chromatography (RPLC) coupled with triple quadrupole mass spectrometry system."	( The pharmacokinetic characters of simvastatin after co-administration with Shexiang Baoxin Pill in healthy volunteers' plasma. Jiang, P; Li, M; Liu, R; Peng, C; Tao, J; Zhang, W, 2016)	0.92
" The method has been successfully applied in clinical pharmacokinetic study in the Indian population."	( Development and Validation of an LC-MS-MS Method for the Simultaneous Determination of Simvastatin, Simvastatin Acid and Ezetimibe in Human Plasma and Its Application to Pharmacokinetic Study in the Indian Population. Bonga, PB; Munaga, SB; Rao, VS; Sharma, HK; Valluru, RK, 2016)	0.66
" Pharmacokinetic parameters were assessed at prespecified intervals."	( Effect of canagliflozin on the pharmacokinetics of glyburide, metformin, and simvastatin in healthy participants. Devineni, D; Mamidi, RN; Manitpisitkul, P; Murphy, J; Skee, D; Stieltjes, H; Tian, H; Usiskin, K; Vandebosch, A; Verhaeghe, T; Wajs, E; Wang, SS, )	0.36
" A new model was developed for the prediction of AUC of statins that utilized the slopes of the above 2 models, with pharmacokinetic (Cmax) and a pharmacodynamic (IC50 value) components for the statins."	( Dual Incorporation of the in vitro Data (IC50) and in vivo (Cmax) Data for the Prediction of Area Under the Curve (AUC) for Statins using Regression Models Developed for Either Pravastatin or Simvastatin. Srinivas, NR, 2016)	0.62
" The method was successfully applied to characterize the pharmacokinetic profiles of SV and SVA following an oral administration of 40 mg SV tablet to healthy human volunteers."	( Development and Validation of an LC-MS-MS Method for Determination of Simvastatin and Simvastatin Acid in Human Plasma: Application to a Pharmacokinetic Study. Monif, T; Partani, P; Verma, SM, 2016)	0.67
" GSK2647544 was readily absorbed and its plasma concentration declined bi-exponentially with a terminal half-life ranging from 8 to 16 hours."	( Evaluation of the safety, pharmacokinetics, pharmacodynamics, and drug-drug interaction potential of a selective Lp-PLA2 inhibitor (GSK2647544) in healthy volunteers . Fong, R; Gray, F; Guiney, W; Lockhart, A; Wu, K; Xu, J; Xu, Y; Yao, X, 2016)	0.43
"OM3-CA did not affect the pharmacokinetics or pharmacodynamics of warfarin or the pharmacodynamic effects of ASA."	( No Effect of Omega-3 Carboxylic Acids on Pharmacokinetics/Pharmacodynamics of Warfarin or on Platelet Function When Co-administered with Acetylsalicylic Acid: Results of Two Phase I Studies in Healthy Volunteers. Davidson, M; Nilsson, C; Offman, E, 2017)	0.46
"The aim of the article was to assess the potential for pharmacokinetic interaction between OM3-CA and the statins rosuvastatin and simvastatin."	( Assessment of pharmacokinetic interaction between omega-3 carboxylic acids and the statins rosuvastatin and simvastatin: Results of 2 phase I studies in healthy volunteers. Davidson, M; Nilsson, C; Offman, E, )	0.55
" Lack of a drug-drug interaction was declared if the 90% confidence interval (CI) of the geometric least-squares mean ratio of pharmacokinetic parameters was in the range 80% to 125%."	( Assessment of pharmacokinetic interaction between omega-3 carboxylic acids and the statins rosuvastatin and simvastatin: Results of 2 phase I studies in healthy volunteers. Davidson, M; Nilsson, C; Offman, E, )	0.34
" Evaluation of potential pharmacodynamic interaction was based on the behavioral tests: elevated plus maze (EPM) test and the Vogel conflict test (VCT)."	( Pharmacodynamic and pharmacokinetic interactions between simvastatin and diazepam in rats. Rutkowska, M; Słupski, W; Trocha, M, 2017)	0.7
"Abolition of diazepam anxiolytic effect during concomitant use of simvastatin is probably caused by diminished bioavailability of diazepam, although pharmacodynamic interaction between these drugs cannot be excluded."	( Pharmacodynamic and pharmacokinetic interactions between simvastatin and diazepam in rats. Rutkowska, M; Słupski, W; Trocha, M, 2017)	0.94
" The aim of this study was to establish a physiologically based pharmacokinetic (PBPK) parent-metabolite model of zoptarelin doxorubicin and to apply it for drug-drug interaction (DDI) potential analysis."	( A physiologically based pharmacokinetic (PBPK) parent-metabolite model of the chemotherapeutic zoptarelin doxorubicin-integration of in vitro results, Phase I and Phase II data and model application for drug-drug interaction potential analysis. Aicher, B; Ammer, N; Britz, H; Hanke, N; Lehr, T; Moj, D; Sindermann, H; Teifel, M; Wojtyniak, JG, 2018)	0.48
" Dissolution and pharmacokinetic studies indicated that the simvastatin/DMβCD complex exhibited an increased dissolution rate, rapid absorption, and improved bioavailability in rats compared to free drug."	( Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats. Fan, H; Gu, F; Ning, J; Wang, Y; Wu, C, 2018)	1
" No significant changes were observed in pharmacokinetic parameters of SV and simvastatin hydroxy acid in the IA plus SV co-treated group in comparison with those in the group treated with SV alone."	( Ilexgenin A enhances the effects of simvastatin on non-alcoholic fatty liver disease without changes in simvastatin pharmacokinetics. Li, P; Lu, YW; Wen, XD; Yang, J; Zhang, L; Zhu, YC, 2018)	0.98
" This study was to investigate whether and how CV drugs affect the pharmacokinetic profile of sinomenine."	( Co-administration with simvastatin or lovastatin alters the pharmacokinetic profile of sinomenine in rats through cytochrome P450-mediated pathways. Dai, Y; Jin, Y; Wang, M; Wang, Y; Xia, Y; Yun, X, 2018)	0.79
" Coadministration of Fbt and Svt with Bbr had no significant effect on the pharmacokinetic parameters of Bbr, except time to maximum concentration, apparent volume of distribution, and apparent clearance."	( Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: an open-label, randomized, parallel study in healthy Chinese subjects. Li, G; Qiu, F; Sun, Y; Zhao, L; Zhao, M, 2019)	0.75
" No clinically obvious pharmacokinetic interactions between Bbr and Fbt/Svt were observed with combined administration."	( Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: an open-label, randomized, parallel study in healthy Chinese subjects. Li, G; Qiu, F; Sun, Y; Zhao, L; Zhao, M, 2019)	0.75
" Plasma concentrations of simvastatin and its active metabolite, simvastatin acid, were measured using liquid chromatography-tandem mass spectrometry for pharmacokinetic assessment."	( Effect of Cilostazol on the Pharmacokinetics of Simvastatin in Healthy Subjects. Ghim, JL; Huh, W; Jung, JA; Kim, JR; Kim, S; Ko, JW; Shin, JG, 2019)	1.07
"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)	0.69
" This method was applied for studying the pharmacokinetic interactions in rats after oral co-administration of silymarin (45 mg/kg) and different concentrations of SV."	( Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats. Ding, CY; Dong, ZJ; Li, Y; Li, YJ; Meng, L; Wu, Y, 2019)	0.76
" The aim of this study was to develop a joint population pharmacokinetic model for simvastatin and four metabolites in children and adolescents to investigate sources of variability in simvastatin acid exposure in this patient population, in addition to SLCO1B1 genotype status."	( A population pharmacokinetic model for simvastatin and its metabolites in children and adolescents. Abdel-Rahman, S; Galetin, A; Leeder, JS; Ogungbenro, K; Wagner, JB, 2019)	1.01
"Plasma concentrations of simvastatin and its four metabolites, demographic and polymorphism data for OATP1B1 and CYP3A5 were analysed utilising a population pharmacokinetic modelling approach from an existing single oral dose (10 mg < 17 years and 20 mg ≥ 18 years) pharmacokinetic dataset of 32 children and adolescents."	( A population pharmacokinetic model for simvastatin and its metabolites in children and adolescents. Abdel-Rahman, S; Galetin, A; Leeder, JS; Ogungbenro, K; Wagner, JB, 2019)	1.09
"The pharmacokinetic (PK) properties of drugs are affected in several ways by interactions with microbiota."	( Impact of Vancomycin-Induced Changes in the Intestinal Microbiota on the Pharmacokinetics of Simvastatin. Cho, JY; Jang, IJ; Ji, SC; Kim, AH; Lee, S; Sunwoo, J; Yu, KS, 2020)	0.78
" The optimized SMV-LST was evaluated for pharmacokinetic parameters and potential hypolipidemic activity on induced hyperlipidemic rats."	( Enhancing the Hypolipidemic Effect of Simvastatin in Poloxamer-Induced Hyperlipidemic Rats via Liquisolid Approach: Pharmacokinetic and Pharmacodynamic Evaluation. Ahmed, OAA; Ahmed, TA; El-Say, KM; Elimam, H, 2020)	0.83
" A rare adverse interaction between simvastatin and abiraterone (Zytiga), an androgen biosynthesis inhibitor, was observed in a patient with mCRPC due to pharmacokinetic changes resulting from obstructive jaundice."	( Statin-Induced Rhabdomyolysis Due to Pharmacokinetic Changes From Biliary Obstruction in a Patient With Metastatic Prostate Cancer. Desikan, R; Desikan, SP; Fisher, A; Sobash, P, )	0.41
" The aim of this study was to fabricate and optimize SIM encapsulated silica-lipid hybrids (SLH) as a solid-state lipid-based formulation to enhance absorption and bioavailability during a human in vivo pharmacokinetic study."	( A safety, tolerability, and pharmacokinetic study of a novel simvastatin silica-lipid hybrid formulation in healthy male participants. Abuhelwa, AY; Clifton, P; Joyce, P; Meola, TR; Prestidge, CA, 2021)	0.86
" Because pharmacodynamic interaction between statins and bempedoic acid is complex, a dose-response model was developed to predict LDL-C pharmacodynamics following administration of statins combined with bempedoic acid."	( Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose-response model. Amore, BM; Barrett, PHR; Catapano, AL; Chapel, S; Crass, RL; Emery, MG; Jadhav, SB; Kerschnitzki, M; Sasiela, WJ; Watts, GF, 2022)	0.72
" We evaluated the use of pharmacokinetic measurements to monitor adherence to simvastatin in patients with coronary heart disease (CHD)."	( Monitoring Simvastatin Adherence in Patients With Coronary Heart Disease: A Proof-of-Concept Study Based on Pharmacokinetic Measurements in Blood Plasma. Andersen, AM; Bergan, S; Fagerland, MW; Husebye, E; Kristiansen, O; Munkhaugen, J; Vethe, NT, 2022)	1.34
" Further studies using physiologically based pharmacokinetic modelling are required to investigate the drug-drug interactions between these drugs."	( Simvastatin, but Not Atorvastatin, Is Associated with Higher Peak Rivaroxaban Serum Levels and Bleeding: an Asian Cohort Study from Singapore. Chan, ECY; Soh, XQ; Tan, DS, 2023)	2.35
"Physiologically-based pharmacokinetic (PBPK) models have an important role in drug discovery/development and decision making in regulatory submissions."	( Does the choice of applied physiologically-based pharmacokinetics platform matter? A case study on simvastatin disposition and drug-drug interaction. Ahlström, C; Lennernäs, H; Lundahl, A; Prieto Garcia, L; Sjögren, E; Vildhede, A, 2022)	0.94

Compound-Compound Interactions

The aim of this study is to observe and analyze the clinical efficacy of simvastatin combined with exercise training in the treatment of stationary chronic obstructive pulmonary disease complicated with metabolic syndrome. Rhabdomyolysis was most likely induced by toxic plasma concentrations of SimVastatin due to Pal.

Excerpt	Reference	Relevance
"Nineteen adult patients with type III hyperlipoproteinemia (HLP) and homozygosity for apolipoprotein (apo) E2 were treated with the 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitor simvastatin (20 or 40 mg per day) alone or in combination with the fibrate derivative gemfibrozil (450 mg per day) during a 30-week outpatient study."	( The influence of simvastatin alone or in combination with gemfibrozil on plasma lipids and lipoproteins in patients with type III hyperlipoproteinemia. Eichinger, M; Feussner, G; Ziegler, R, 1992)	0.81
"We have studied the effect of simvastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, alone and in combination with cholestyramine in 48 patients."	( [HMG-CoA reductase inhibitors in familial hypercholesterolemia. Therapy with simvastatin alone and in combination with cholestyramine in low dosage; a report of 2 years experiences]. Burrichter, H; Geisel, J; Oette, K, 1990)	0.8
" The use of Simvastatin in combination with HELP significantly augments the reduction in LDL cholesterol to a level where regression of atherosclerotic lesions might be expected."	( Long-term clinical experience with HELP-LDL-apheresis in combination with HMG-CoA-reductase inhibitors for maximum treatment of coronary heart disease associated with severe hypercholesterolemia. Armstrong, VW; Eisenhauer, T; Scheler, F; Schuff-Werner, P; Schütz, E; Seidel, D; Thiery, J, )	0.51
"Recent trials have investigated the usefulness of fenofibrate, alone and in combination with other lipid-lowering therapies, in the treatment of hyperlipidemia."	( Review of clinical studies of fenofibrate in combination with currently approved lipid-lowering drugs. Brown, WV, 1989)	0.28
" Judging from these results, SV was considered to interact with CT by the following procedure: SV underwent hydrolysis to SVH in aqueous solution, then CT activated the hydrolysis by binding the formed SVH, resulting in a significant reduction in concentration of SV."	( Drug interaction between simvastatin and cholestyramine in vitro and in vivo. Ichikawa, M; Matsuyama, K; Nakai, A; Nishikata, M, 1996)	0.6
" Hormone replacement therapy combined with simvastatin is well tolerated and extremely effective, as the two therapies seem to be additive."	( The effect of hormone replacement therapy alone and in combination with simvastatin on plasma lipids of hypercholesterolemic postmenopausal women with coronary artery disease. Kyriakides, ZS; Sbarouni, E, 1998)	0.8
"To evaluate the effects of simvastatin only or combined with continuous hormone replacement therapy on the serum lipid profile in hypercholesterolaemic post-menopausal women."	( Effects of simvastatin only or in combination with continuous combined hormone replacement therapy on serum lipid levels in hypercholesterolaemic post-menopausal women. Atagündüz, P; Caymaz, O; Erenus, M; Fak, AS; Oktay, A; Oktay, S; Tezcan, H, 2000)	0.99
"The aim of the study was to evaluate the effects of transdermal sequential combined hormone replacement therapy alone or combined with simvastatin on the serum lipid profile in hypercholesterolaemic post-menopausal women."	( [Serum lipid levels in hypercholesterolemic post-menopausal women treated with transdermal sequential combined hormone replacement therapy only or in combination with simvastatin]. Dobrzycka, B; Dobrzycki, S; Kulikowski, M; Lenczewski, A; Mirończuk, J; Nowak, A; Terlikowski, S, 2000)	0.71
" A physiologically-based pharmacokinetic model was used to predict the maximum in vivo drug-drug interaction."	( Inhibition of in vitro metabolism of simvastatin by itraconazole in humans and prediction of in vivo drug-drug interactions. Ikeda, T; Inoue, S; Ishigam, M; Ito, K; Iwabuchi, H; Komai, T; Kondo, T; Sugiyama, Y; Takasaki, W; Uchiyama, M, 2001)	0.58
" Therefore, we examined the effect of an HMG-CoA reductase inhibitor (simvastatin) alone and in combination with cytosine arabinoside (ARA-C) on the proliferation of two AML cell lines."	( Effect of simvastatin alone and in combination with cytosine arabinoside on the proliferation of myeloid leukemia cell lines. Bar-Sef, A; Elis, A; Fabian, I; Lishner, M, 2001)	0.95
"The objective of our study was to evaluate in humans the drug-drug interaction occurring during the concomitant administration of cisapride and simvastatin, two well-known substrates of CYP3A4."	( Study of the drug-drug interaction between simvastatin and cisapride in man. Guilbaud, R; Masseé, R; O'Hara, GE; Prévost, J; Simard, C; Turgeon, J, 2001)	0.77
"The objectives of this review are to discuss the role of cytochrome P450 (CYP450) isoforms in drug metabolism, to explain differences in metabolism among the HMG-CoA reductase inhibitors (HMGs, statins), to review drug-drug and drug-food interaction studies dealing with the HMGs, to present case reports dealing with HMG-related myopathy, to discuss major clinical implications of these case reports and to express an opinion of use of HMGs in clinical practice."	( The role of cytochrome P450-mediated drug-drug interactions in determining the safety of statins. Bottorff, M; Worz, CR, 2001)	0.31
" Therefore, we determined the effect of SCH 48461 and ezetimibe in combination with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors in chow-fed dogs."	( The synergistic hypocholesterolemic activity of the potent cholesterol absorption inhibitor, ezetimibe, in combination with 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors in dogs. Alton, KB; Burrier, RE; Davis, HR; Pula, KK; Watkins, RW, 2001)	0.31
"The purpose of this study was to assess the efficacy and safety of ezetimibe administered with simvastatin in patients with primary hypercholesterolemia."	( Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. Bettis, R; Davidson, MH; LeBeaut, AP; Lipka, LJ; McGarry, T; Melani, L; Sun, S; Suresh, R; Veltri, EP, 2002)	0.82
"To evaluate the effects of simvastatin only or combined with continuous transdermal hormone replacement therapy (HRT) on the serum lipid profile in hypercholesterolaemic women."	( [Effects of simvastatin only or in combination with continuous combined hormone replacement therapy on lipid levels in hypercholesterolemic women]. Dobrzycka, B; Dobrzycki, S; Kulikowski, M; Lenczewski, A; Terlikowski, S, 2003)	0.99
" Rhabdomyolysis can occur with all statins when used alone and particularly when combined with other drugs that are themselves myotoxic or that elevate the concentration of the statin."	( Potential drug interaction between simvastatin and danazol causing rhabdomyolysis. Andreou, ER; Ledger, S, 2003)	0.6
" Pravastatin does not appear to interact with warfarin but has caused an increased INR when combined with the anticoagulant fluindione."	( Oral anticoagulant drug interactions with statins: case report of fluvastatin and review of the literature. Andrus, MR, 2004)	0.32
" A randomized, double-blind, placebo-controlled, crossover trial was conducted with 50 hypercholesterolemic patients with simvastatin and either placebo or ramipril (study I) and in 45 hypercholesterolemic diabetic patients with simvastatin or ramipril with placebo or simvastatin combined with ramipril (study II) for 2 months with 2 months washout."	( Simvastatin combined with ramipril treatment in hypercholesterolemic patients. Ahn, JY; Chung, WJ; Han, SH; Jin, DK; Kang, WC; Kim, DS; Kim, HS; Koh, KK; Seo, YH; Shin, EK; Son, JW, 2004)	1.97
"To evaluate the effects of simvastatin combined with omega-3 fatty acids on high sensitive C-reactive protein (HsCRP), lipidemia, and fibrinolysis in coronary heart disease (CHD) and CHD risk equivalent patients with mixed dyslipidemia."	( Effects of simvastain combined with omega-3 fatty acids on high sensitive C-reactive protein, lipidemia, and fibrinolysis in patients with mixed dyslipidemia. Cui, L; Guo, WJ; Hong, H; Mao, YL; Pang, BS; Wei, Y; Xu, ZM; Yang, XC, 2004)	0.62
" Following with the treatment of patients whose low-density lipoprotein cholesterol (LDL-ch) reaching goal level (< 100 mg/dL) or close to the goal (< 130 mg/dL), while triglyceride (TG) > or = 200 mg/dL and < 500 mg/dL, was combined with omega-3 fatty acids (3 g/d) or a placebo for 2 months."	( Effects of simvastain combined with omega-3 fatty acids on high sensitive C-reactive protein, lipidemia, and fibrinolysis in patients with mixed dyslipidemia. Cui, L; Guo, WJ; Hong, H; Mao, YL; Pang, BS; Wei, Y; Xu, ZM; Yang, XC, 2004)	0.32
" Simvastatin alone or combined with ramipril significantly changed lipoproteins, and improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements by 33 +/- 6% and by 50 +/- 14%, respectively (both P <0."	( Vascular effects of simvastatin combined with ramipril in hypercholesterolemic patients with coronary artery disease, compared with simvastatin alone: a randomized, double-blind, placebo-controlled, crossover study. Ahn, JY; Chung, WJ; Han, SH; Jin, DK; Kim, DS; Kim, HS; Koh, KK; Park, GS; Shin, EK; Son, JW, 2004)	1.56
"Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic, hypertensive patients."	( Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients. Ahn, JY; Ahn, TH; Choi, IS; Chung, WJ; Han, SH; Kang, MH; Koh, KK; Quon, MJ; Seo, YH; Shin, EK, 2004)	2.01
" The aims of the present study were to investigate, in the New Zealand genetically hypertensive (GH) rat model, the effects of treatment with simvastatin, alone or in combination with valsartan or enalapril, on blood pressure (BP) and structural remodelling of mesenteric resistance arteries (MRA) and of the basilar artery, an artery that plays a major role in the regulation of cerebral resistance."	( Effect of simvastatin given alone and in combination with valsartan or enalapril on blood pressure and the structure of mesenteric resistance arteries and the basilar artery in the genetically hypertensive rat model. Laverty, R; Ledingham, JM, )	0.73
" Since DDIs are associated with adverse reactions, we performed a cross-sectional study to assess the prevalence of potentially critical drug-drug and drug-statin interactions in an outpatient adult population with dyslipidaemia."	( Prevalence of potentially severe drug-drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy. Hess, L; Krähenbühl, S; Krähenbühl-Melcher, A; Rätz Bravo, AE; Schlienger, RG; Tchambaz, L, 2005)	0.33
"An inappropriate drug combination was found in approximately 2% of the person-years of data, and persons who experienced an inappropriate drug combination had higher claims costs."	( Inappropriate drug combinations among privately insured patients with HIV disease. Encinosa, WE; Hellinger, FJ, 2005)	0.33
"To evaluate the effectiveness and safety of Taizhi'an (TZA) capsule combined with Simvastatin (Sim) in treating hyperlipidemia in diabetes mellitus (DM) patients."	( Effect of Taizhi'an capsule combined with Simvastatin on hyperlipidemia in diabetic patients. Gao, F; Hu, XF, 2006)	0.82
" In combination with dexamethasone and doxorubicin, statins have a chemo-sensitizing effect."	( Dose-finding study of high-dose simvastatin combined with standard chemotherapy in patients with relapsed or refractory myeloma or lymphoma. Bloem, AC; Bogers, LH; de Weerdt, O; Kramer, MH; Lokhorst, HM; van de Donk, NW; van der Griend, R; van der Spek, E; Wittebol, S, 2006)	0.62
"An 84-year-old man was admitted to the hospital for severe rhabdomyolysis induced by drug-drug interactions between simvastatin and ketoconazole and he recovered completely."	( A lesson for everyone in drug-drug interactions. Akram, K; Parker, M; Rao, S, 2007)	0.55
"Hepatic uptake carriers of the organic anion-transporting peptide (OATP) family of solute carriers are more and more recognized as being involved in hepatic elimination of many drugs and potentially associated drug-drug interactions."	( Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Brun, ME; Funk, C; Noé, J; Portmann, R, 2007)	0.34
"001) or in combination with L-arginine (9."	( Asymmetric dimethylarginine determines the improvement of endothelium-dependent vasodilation by simvastatin: Effect of combination with oral L-arginine. Benndorf, RA; Bierend, A; Böger, GI; Böger, RH; Dumbadze, E; Maas, R; Rudolph, TK; Schwedhelm, E, 2007)	0.56
" At present a drug combination comprising ezetimibe 10 mg and simvastatin in all doses (10, 20, 40 and 80 mg) is being introduced into our market under the company name Inegy."	( [Dual inhibition of cholesterol using the drug combination ezetimibe/simvastatin?]. Vaverková, H, 2007)	0.81
" The frequency of drug-drug interactions involving lovastatin or simvastatin was studied."	( Frequency and clinical relevance of drug interactions with lovastatin and simvastatin: an observational database study. Huupponen, R; Irjala, K; Klaukka, T; Laine, K; Ryynänen, A; Tirkkonen, T; Vahlberg, T, 2008)	0.81
" We established whether ezetimibe combined with simvastatin differently influences post fat load lipid levels and lipoprotein composition as compared to simvastatin 80mg monotherapy in obese male metabolic syndrome patients."	( The effect of statin alone or in combination with ezetimibe on postprandial lipoprotein composition in obese metabolic syndrome patients. Dallinga-Thie, GM; Hajer, GR; van Vark-van der Zee, LC; Visseren, FL, 2009)	0.61
" A comprehensive, controlled clinical trial programme was thus designed to evaluate three separate statins in combination with ABT-335, a new formulation of fenofibric acid."	( Evaluation of a new formulation of fenofibric acid, ABT-335, co-administered with statins : study design and rationale of a phase III clinical programme. Bays, HE; Buttler, SM; Davidson, MH; Jones, PH; Kelly, MT; Setze, CM; Sleep, DJ; Stolzenbach, JC, 2008)	0.35
"We investigated the role of Valsartan (V) alone or in combination with Simvastatin (S) on coronary atherosclerosis and vascular remodeling, and tested the hypothesis that V or V/S attenuate the pro-inflammatory effect of low endothelial shear stress (ESS)."	( Attenuation of inflammation and expansive remodeling by Valsartan alone or in combination with Simvastatin in high-risk coronary atherosclerotic plaques. Baker, AB; Beigel, R; Chatzizisis, YS; Coskun, AU; Daley, W; Edelman, ER; Feldman, CL; Gerrity, RG; Jonas, M; Maynard, C; Stone, BV; Stone, PH, 2009)	0.8
"5 mg) combined with alpha-TCP particles or left empty."	( Effects of the combination with alpha-tricalcium phosphate and simvastatin on bone regeneration. Kasugai, S; Kihara, H; Machida, T; Nyan, M; Ohya, K; Sato, D, 2009)	0.59
" Effects on TAG were also present in combination with statin treatment, illustrating an additional benefit of stanol esters in this CHD risk population."	( A plant stanol yogurt drink alone or combined with a low-dose statin lowers serum triacylglycerol and non-HDL cholesterol in metabolic syndrome patients. Brufau, G; Dallinga-Thie, GM; Dasselaar, M; Mensink, RP; Plat, J, 2009)	0.35
"We have previously reported that healing of rat calvarial defects was enhanced by application of alpha tricalcium phosphate (alphaTCP) combined with simvastatin, a cholesterol synthesis inhibitor."	( Molecular and tissue responses in the healing of rat calvarial defects after local application of simvastatin combined with alpha tricalcium phosphate. Hao, J; Kasugai, S; Kuroda, S; Miyahara, T; Noritake, K; Nyan, M; Rodriguez, R, 2010)	0.78
"We evaluated the bioavailability of each ingredient of the Polycap and determined any drug-drug interactions relative to single component reference preparations."	( Preservation of bioavailability of ingredients and lack of drug-drug interactions in a novel five-ingredient polypill (polycap): a five-arm phase I crossover trial in healthy volunteers. Chakraborty, BS; Desai, J; Ghosh, C; Jha, V; Khamar, B; Patel, A; Shah, G; Shah, T, 2010)	0.36
"Comparative bioavailability was computed and no drug-drug interactions and no difference in comparative bioavailability were concluded for each ingredient based on point estimates of the T/R ratio of the geometric means falling within 80-125% for peak plasma concentration (C(max)), area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC(t)), and AUC from time zero to infinity (AUC(infinity))."	( Preservation of bioavailability of ingredients and lack of drug-drug interactions in a novel five-ingredient polypill (polycap): a five-arm phase I crossover trial in healthy volunteers. Chakraborty, BS; Desai, J; Ghosh, C; Jha, V; Khamar, B; Patel, A; Shah, G; Shah, T, 2010)	0.36
" The present study in healthy volunteers establishes that Polycap is safe (no serious adverse events) and well tolerated, and that there is no indication of pharmacokinetic drug-drug interactions for any of the ingredients, with their bioavailabilities being well preserved."	( Preservation of bioavailability of ingredients and lack of drug-drug interactions in a novel five-ingredient polypill (polycap): a five-arm phase I crossover trial in healthy volunteers. Chakraborty, BS; Desai, J; Ghosh, C; Jha, V; Khamar, B; Patel, A; Shah, G; Shah, T, 2010)	0.36
" It is in clinical development for the prevention of cardiovascular events and will likely be used in combination with standard of care, including statins."	( Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin: no clinically relevant drug-drug interactions. Abt, M; Bech, N; Derks, M; Meneses-Lorente, G; Parr, G; Phelan, M; Turnbull, L; White, AM, 2010)	0.6
" This effect was offset when simvastatin was combined with ezetimibe (LDL-IVB +14."	( Ezetimibe alone or in combination with simvastatin increases small dense low-density lipoproteins in healthy men: a randomized trial. Berneis, K; Berthold, HK; Gouni-Berthold, I; Krone, W; Rizzo, M; Spinas, GA, 2010)	0.92
"To investigate the protective effects of simvastatin (Sim) combined with nifedipine (Nif) on endothelial cells and elucidate the action mechanism."	( Simvastatin combined with nifedipine enhances endothelial cell protection by inhibiting ROS generation and activating Akt phosphorylation. Chen, XN; Fan, M; Feng, Z; Han, JY; Xu, J; Yang, Z, 2010)	2.07
" Results indicated it was possible to prepare high-dose sustained-release NA pellets combined with little-dose immediate release SIM by spraying double EC polymer and SIM milled suspension on NA pellets in a bottom-spray fluidized bed coater, respectively."	( Preparation and evaluation of nicotinic acid sustained-release pellets combined with immediate release simvastatin. Guan, T; Hong, M; Li, G; Tang, X; Tao, X; Zhang, L; Zhao, X, 2010)	0.58
" Food and Drug Administration draft drug interaction guidance as CYP3A4 inducers for clinical drug-drug interaction (DDI) studies."	( Simulation of clinical drug-drug interactions from hepatocyte CYP3A4 induction data and its potential utility in trial designs. Hayashi, M; Shou, M; Skiles, GL; Xu, Y; Zhou, Y, 2011)	0.37
"We compared the effect of simvastatin versus simvastatin combined with ezetimibe on hemostasis and inflammation after acute coronary events [acute coronary syndromes (ACS)]."	( Ezetimibe combined with simvastatin compared with simvastatin alone results in a greater suppression of oxidative stress and enhanced fibrinolysis in patients after acute coronary events. Machnik, A; Potaczek, DP; Tracz, W; Undas, A; Wypasek, E; Zmudka, K, 2011)	0.98
"The purpose of this study is to evaluate the osteoconductivity of three different bone substitute materials: α-tricalcium phosphate (α-TCP), (β-TCP), and hydroxyapatite (HA), combined with or without simvastatin, which is a cholesterol synthesis inhibitor stimulating BMP-2 expression in osteoblasts."	( Evaluation of the osteoconductivity of α-tricalcium phosphate, β-tricalcium phosphate, and hydroxyapatite combined with or without simvastatin in rat calvarial defect. Kasugai, S; Nyan, M; Ohya, K; Rojbani, H, 2011)	0.76
" The aim of this study was to evaluate the effects of losartan or amlodipine alone or combined with simvastatin on hepatic steatosis degree, and on insulin sensitivity in normocholesterolemic, hypertensive patients with nonalcoholic hepatic steatosis."	( Effects of losartan and amlodipine alone or combined with simvastatin in hypertensive patients with nonalcoholic hepatic steatosis. Derosa, G; Fogari, R; Lazzari, P; Maffioli, P; Mugellini, A; Zoppi, A, 2012)	0.84
"The incidence of paradoxical HDL-C reductions was low in mixed dyslipidemic patients receiving FENO alone or combined with EZE or EZE/SIMVA."	( Low incidence of paradoxical reductions in HDL-C levels in dyslipidemic patients treated with fenofibrate alone or in combination with ezetimibe or ezetimibe/simvastatin. Brudi, P; Dong, Q; Farnier, M; Johnson-Levonas, AO; Shah, A, 2011)	0.57
" Few studies have documented the efficacy and safety of CETP inhibitors in combination with commonly used statins."	( Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. Brewer, HB; Hu, B; Kastelein, JJ; Krueger, KA; McErlean, E; Nicholls, SJ; Nissen, SE; Shao, M; Wang, MD, 2011)	0.37
"To examine the biochemical effects, safety, and tolerability of evacetrapib, as monotherapy and in combination with statins, in patients with dyslipidemia."	( Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. Brewer, HB; Hu, B; Kastelein, JJ; Krueger, KA; McErlean, E; Nicholls, SJ; Nissen, SE; Shao, M; Wang, MD, 2011)	0.37
" In combination with statin therapy, evacetrapib, 100 mg/d, produced increases in HDL-C of 42."	( Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. Brewer, HB; Hu, B; Kastelein, JJ; Krueger, KA; McErlean, E; Nicholls, SJ; Nissen, SE; Shao, M; Wang, MD, 2011)	0.37
"Compared with placebo or statin monotherapy, evacetrapib as monotherapy or in combination with statins increased HDL-C levels and decreased LDL-C levels."	( Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. Brewer, HB; Hu, B; Kastelein, JJ; Krueger, KA; McErlean, E; Nicholls, SJ; Nissen, SE; Shao, M; Wang, MD, 2011)	0.37
" Our aims were to prospectively assess the antiviral efficacy and safety of this drug combination in chronic hepatitis C (CHC) patients."	( Open-label phase 1b pilot study to assess the antiviral efficacy of simvastatin combined with sertraline in chronic hepatitis C patients. Altmeyer, R; Cheng, CW; Chopra, N; Lawitz, E; Lim, SG; McHutchison, JG; Patel, K; Randle, JC; Tillmann, HL, 2011)	0.6
" Mean plasma concentration-time profiles for atazanavir, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), darunavir (DRV, administered with ritonavir [RTV]), and drospirenone/ethinylestradiol were similar following co-administration of GSK2248761."	( Drug interaction profile for GSK2248761, a next generation non-nucleoside reverse transcriptase inhibitor. de Serres, M; Gould, E; Johnson, M; Kim, J; Lou, Y; Mayers, D; Pietropaolo, K; Piscitelli, S; White, S; Zhou, XJ, 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
" We investigated the effect of simvastatin monotherapy or its combination with ezetimibe on TLR2 and TLR4 membrane expression and on lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β) and interleukin-6 (IL-6) production in peripheral blood monocytes of patients with primary hypercholesterolemia."	( Effect of simvastatin or its combination with ezetimibe on Toll-like receptor expression and lipopolysaccharide - induced cytokine production in monocytes of hypercholesterolemic patients. Elisaf, MS; Liberopoulos, EN; Milionis, HJ; Moutzouri, E; Rousouli, K; Tellis, CC; Tselepis, AD, 2012)	1.07
" This study aimed to investigate the effects of simvastatin locally applied from calcium sulfate (CS) combined with a mesenchymal stem cell (MSC) sheet on fracture healing."	( Mesenchymal stem cell sheet transplantation combined with locally released simvastatin enhances bone formation in a rat tibia osteotomy model. Qi, Y; Shi, Z; Wang, J; Xu, K; Yan, W; Zhao, T, 2013)	0.88
" This investigation assessed risk for myopathy in patients receiving treatment with a statin in combination with daptomycin, a medication also associated with muscle injury."	( Statins and daptomycin: safety assessment of concurrent use and evaluation of drug interaction liability. Barber, GR; Barron, MA; Golightly, LK; Page, RL, 2013)	0.39
" Risk of muscle injury therefore appears to be no greater when a statin is administered with daptomycin than when either medication is used alone."	( Statins and daptomycin: safety assessment of concurrent use and evaluation of drug interaction liability. Barber, GR; Barron, MA; Golightly, LK; Page, RL, 2013)	0.39
"The administration of simvastatin and EPC transplantation can reduce the severity of LPS-induced ALI in mice, and improvement is moderately enhanced in some respects when EPC transplantation is combined with simvastatin administration."	( Repair of lipopolysaccharide-induced acute lung injury in mice by endothelial progenitor cells, alone and in combination with simvastatin. Jing, H; Li, H; Qiang, Y; Wang, G; Wang, L; Wu, H; Yi, J, 2013)	0.91
"To evaluate the effects and safety of policosanol combined with simvastatin on serum lipids and sex hormones in male patients with hyperlipidemia."	( [Effects of policosanol combined with simvastatin on serum lipids and sex hormones in male patients with hyperlipidemia]. Gong, X; Tang, M; Wu, SZ, 2013)	0.9
" The application of SOHGA for automated model selection, combined with traditional model selection strategies, appears to save time for model development, which also can generate new hypotheses that are biologically more plausible."	( Genetic algorithm guided population pharmacokinetic model development for simvastatin, concurrently or non-concurrently co-administered with amlodipine. Chaturvedula, A; Lee, H; Sale, ME, 2014)	0.63
"Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in corn in combination with deoxynivalenol (DON) and zearalenone."	( Effects of fumonisin B1 alone and combined with deoxynivalenol or zearalenone on porcine granulosa cell proliferation and steroid production. Caloni, F; Cortinovis, C; Schreiber, NB; Spicer, LJ, 2014)	0.4
"A dispersive liquid-liquid microextraction method based on solidification of floating organic drop combined with HPLC was developed for the determination of lovastatin and simvastatin in rat urine for the first time."	( A dispersive liquid-liquid microextraction method based on the solidification of a floating organic drop combined with HPLC for the determination of lovastatin and simvastatin in rat urine. Hou, X; Li, F; Ma, X; Wang, L; Zhao, L; Zhao, P, 2014)	0.79
" This purpose of this study was to determine whether simvastatin combined with an antioxidant could produce the same effect or greater and to examine affected surrogate biomarkers for the neuroinflammation after traumatic brain injury in rat."	( Simvastatin combined with antioxidant attenuates the cerebral vascular endothelial inflammatory response in a rat traumatic brain injury. Chen, HJ; Cho, CL; Liang, CL; Liliang, PC; Lu, K; Tsai, YD; Wang, HK; Wang, KW, 2014)	2.09
"Almost 50% of serious adverse events with statin therapy are attributed to unfavorable drug-drug combinations."	( Avoiding patient morbidity: Updated statin drug interactions and risks for patient harm. Campbell, JD; Finks, SW, 2014)	0.4
" We aimed to develop a mathematical model describing a drug-drug interaction between simvastatin and clarithromycin in humans."	( A pharmacokinetic drug-drug interaction model of simvastatin and clarithromycin in humans. Chaiwong, K; Lohitnavy, M; Methaneethorn, J; Pongpanich, K; Sonsingh, P, 2014)	0.88
"The drug-drug interaction between simvastatin and clarithromycin was modeled simultaneously with a parent-metabolite model for clarithromycin and a one-compartment model for simvastatin linked to its active form, simvastatin hydroxy acid."	( A pharmacokinetic drug-drug interaction model of simvastatin and clarithromycin in humans. Chaiwong, K; Lohitnavy, M; Methaneethorn, J; Pongpanich, K; Sonsingh, P, 2014)	0.94
" Therefore, we aimed to develop a mathematical model describing drug-drug interaction between simvastatin and verapamil in humans."	( A pharmacokinetic drug-drug interaction model of simvastatin and verapamil in humans. Chamnansua, M; Kaewdang, N; Lohitnavy, M; Methaneethorn, J, 2014)	0.88
"The drug-drug interaction between simvastatin and verapamil was modeled simultaneously with a two compartment model for verapamil with its active metabolite, norverapamil and a one compartment model for simvastatin with its active form, simvastatin hydroxy acid."	( A pharmacokinetic drug-drug interaction model of simvastatin and verapamil in humans. Chamnansua, M; Kaewdang, N; Lohitnavy, M; Methaneethorn, J, 2014)	0.94
"Forty rabbits were randomly divided into five groups of eight: normal control, hyperlipidemia model, pioglitazone, simvastatin, and pioglitazone combined with simvastatin therapy."	( Effect of pioglitazone combined with simvastatin on the CD40-CD40 ligand system in rabbits with atherosclerosis. Bao, XC; Gao, XQ; Ji, XP; Li, HW; Qiu, YH; Wu, Z; Xue, L; Yang, XF; Zhu, XH, 2015)	0.9
" Accordingly, potential drug-drug interactions associated with the concomitant use of these agents present an area of concern."	( Carboxylesterase 1-mediated drug-drug interactions between clopidogrel and simvastatin. Markowitz, JS; Wang, X; Zhu, HJ, 2015)	0.65
"Simvastatin given in combination with aspirin delayed the development of pathological changes in the myocardium, reduced vascular damage and prolonged the survival time of cardiac allograft."	( Simvastatin combined with aspirin increases the survival time of heart allograft by activating CD4(+)CD25(+) Treg cells and enhancing vascular endothelial cell protection. Gao, B; Zhu, J, )	3.02
" Fifty-one in each group were given placebo, ezetimibe 10mg combined with simvastatin 10mg (Vyto10), ezetimibe 10mg combined with simvastatin 20mg (Vyto20), or simvastatin 20mg alone (Simva20) daily for 2months."	( Vascular and metabolic effects of ezetimibe combined with simvastatin in patients with hypercholesterolemia. Han, SH; Hayashi, T; Kim, EY; Koh, KK; Lee, Y; Oh, PC; Park, YM; Sakuma, I; Shin, EK, 2015)	0.89
" CETP inhibitors are likely to be utilized as 'add-on' therapy to statins in patients receiving concomitant medications, so the potential for evacetrapib to cause clinically important drug-drug interactions (DDIs) with cytochromes P450 (CYP) was evaluated."	( CYP-mediated drug-drug interactions with evacetrapib, an investigational CETP inhibitor: in vitro prediction and clinical outcome. Cannady, EA; Friedrich, S; Krueger, KA; Nicholls, SJ; Rehmel, JR; Suico, JG; Wang, MD, 2015)	0.42
"The aim of this study was to evaluate the effects of perindopril or barnidipine alone or combined with simvastatin on metabolic parameters and hepatic steatosis degree."	( Perindopril and barnidipine alone or combined with simvastatin on hepatic steatosis and inflammatory parameters in hypertensive patients. D'Angelo, A; Derosa, G; Maffioli, P; Mugellini, A; Pesce, RM, 2015)	0.88
" The proposed method was applied to the drug-drug pharmacokinetic interaction study of SV combined with BBR after oral administration in rats."	( Validated UPLC-MS/MS method for simultaneous determination of simvastatin, simvastatin hydroxy acid and berberine in rat plasma: Application to the drug-drug pharmacokinetic interaction study of simvastatin combined with berberine after oral administratio Li, G; Liu, M; Su, X; Zhao, G; Zhao, L, 2015)	0.66
" Because of interaction between amlodipine and simvastatin, in combination with physical activity, the patient reported: muscle pain, weakness of the muscles, dizziness, and confusion."	( [Drug interaction in 63-year-old male sportsman--a case report]. Foerster, J; Schetz, D; Sein Anand, J, 2015)	0.67
" Materials and methods In the present study, we investigated whether SV combined with BGM mediates its effect through suppression of NF-κB-signalling pathway."	( Simvastatin in combination with bergamottin potentiates TNF-induced apoptosis through modulation of NF-κB signalling pathway in human chronic myelogenous leukaemia. Ahn, KS; Kim, SM; Lee, EJ; Lee, JH; Lee, SG; Nam, D; Shim, BS; Um, JY; Yang, WM, 2016)	1.88
" In this clinical study, 26 healthy subjects received simvastatin 40 mg alone or in combination with LCZ696 or after 1 or 2 h of LCZ696 dosing."	( In vitro and clinical evaluation of OATP-mediated drug interaction potential of sacubitril/valsartan (LCZ696). Alexander, N; Ayalasomayajula, S; Goswami, B; Han, Y; Hanna, I; Hinder, M; Langenickel, T; Malcolm, K; Natrillo, A; Sunkara, G; Zhou, W, 2016)	0.68
" 20 patients (32 hips) underwent multiple drilling combined with simvastatin treatment (SIM group); 16 patients (26 hips) underwent multiple drilling alone (MD group)."	( Multiple drilling combined with simvastatin versus multiple drilling alone for the treatment of avascular osteonecrosis of the femoral head: 3-year follow-up study. Wang, D; Yin, H; Yuan, Z, 2016)	0.96
" Muscle biopsy was compatible with statin-associated rhabdomyolysis, probably caused by a drug-drug interaction between simvastatin and itraconazole."	( Statin-associated rhabdomyolysis triggered by drug-drug interaction with itraconazole. Damkier, P; Dybro, AM; Hellfritzsch, M; Rasmussen, TB, 2016)	0.64
"To evaluate in healthy volunteers the safety, pharmacokinetics (PK), pharmacodynamics (PD), and drug-drug interaction (DDI) potential of GSK2647544, (a selective lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor)."	( Evaluation of the safety, pharmacokinetics, pharmacodynamics, and drug-drug interaction potential of a selective Lp-PLA2 inhibitor (GSK2647544) in healthy volunteers . Fong, R; Gray, F; Guiney, W; Lockhart, A; Wu, K; Xu, J; Xu, Y; Yao, X, 2016)	0.43
" The purpose of this study is to elucidate the role of hyperlipidaemia alone or in combination with acidosis/alkalosis in the development and potentiation of statin-induced myotoxicity."	( Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity. Barrett, DA; Bruce, KD; de Moor, CH; Eckel, RH; Gershkovich, P; Lee, JB; Sungelo, M; Taha, DA; Zgair, A, 2017)	0.46
" The study compared the effect of physical exercise on the changes of serum potassium in hypertensive patients receiving ACEI alone or in combination with statin."	( Short-term changes of serum potassium concentration induced by physical exercise in patient with arterial hypertension treated with angiotensin-converting enzyme inhibitor alone or in combination with statin. Deska, P; Nowicki, M, 2017)	0.46
" The aim of this study was to establish a physiologically based pharmacokinetic (PBPK) parent-metabolite model of zoptarelin doxorubicin and to apply it for drug-drug interaction (DDI) potential analysis."	( A physiologically based pharmacokinetic (PBPK) parent-metabolite model of the chemotherapeutic zoptarelin doxorubicin-integration of in vitro results, Phase I and Phase II data and model application for drug-drug interaction potential analysis. Aicher, B; Ammer, N; Britz, H; Hanke, N; Lehr, T; Moj, D; Sindermann, H; Teifel, M; Wojtyniak, JG, 2018)	0.48
" A combination of in vitro data, clinical pharmacokinetic data, and drug-drug interaction (DDI) data of osimertinib in oncology patients were used to develop the physiologically based pharmacokinetic (PBPK) model and verify the DDI data of osimertinib."	( Development, Verification, and Prediction of Osimertinib Drug-Drug Interactions Using PBPK Modeling Approach to Inform Drug Label. Ballard, P; Pilla Reddy, V; Sharma, P; Vishwanathan, K; Walker, M, 2018)	0.48
" The aim of the present study was to investigate the roles and mechanisms of low‑frequency ultrasound (LFU) and microbubbles combined with simvastatin on MCF‑7 cell growth and apoptosis."	( Low‑frequency ultrasound and microbubbles combined with simvastatin promote the apoptosis of MCF‑7 cells by affecting the LATS1/YAP/RHAMM pathway. Chen, C; Li, H; Wang, D, 2018)	0.93
" Due to drug-drug interactions caused by the inhibition or induction of cytochrome P450 enzymes, changes in drug metabolism are the major causes of drug toxicity, CYP3A4 is one of the key isozymes, and involved in the metabolism of over 60% of clinical drugs."	( The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins. Fang, L; Fang, Q; Feng, P; Guo, F; Li, B; Liang, Z; Xu, X; Zhan, G; Zhang, B; Zhao, L, 2018)	0.48
" We aimed to investigate the differential association of ezetimibe-statin combination with incident MACE by presence of diabetes."	( Differential association of ezetimibe-simvastatin combination with major adverse cardiovascular events in patients with or without diabetes: a retrospective propensity score-matched cohort study. Cha, BS; Hong, N; Kang, ES; Lee, BW; Lee, CJ; Lee, YH; Park, SH, 2018)	0.75
"A previous attempt to accurately quantify the increased simvastatin acid exposure due to drug-drug interaction (DDI) with coadministered telithromycin, using a mechanistic static model, substantially underpredicted the magnitude of the area under the plasma concentration-time curve ratio (AUCR) based on reversible inhibition of CYP3A4 and organic anion transporting polypeptide 1B1 (OATP1B1)."	( Mechanistic In Vitro Studies Indicate that the Clinical Drug-Drug Interaction between Telithromycin and Simvastatin Acid Is Driven by Time-Dependent Inhibition of CYP3A4 with Minimal Effect on OATP1B1. Butler, P; Elsby, R; Gill, RU; Hare, V; Neal, H; Outteridge, S; Pearson, C; Plant, K; Riley, RJ, 2019)	0.97
"Five clinical pharmacology studies evaluated the potential drug-drug interaction between multiple subcutaneous taspoglutide doses and a single dose of lisinopril, warfarin, and simvastatin and multiple doses of digoxin and an oral contraceptive containing ethinylestradiol and levonorgestrel."	( Assessment of Drug-Drug Interactions between Taspoglutide, a Glucagon-Like Peptide-1 Agonist, and Drugs Commonly Used in Type 2 Diabetes Mellitus: Results of Five Phase I Trials. Bogman, K; Brumm, J; Giraudon, M; Hofmann, C; Mangold, B; Niggli, M; Sauter, A; Schmitt, C; Sturm, S; Sturm-Pellanda, C, 2019)	0.71
"The objective of this study was to fabricate and characterize chitosan combined with different amounts of simvastatin-loaded nanoparticles and to investigate their potential for guided bone regeneration in vitro and in vivo."	( In vitro and in vivo evaluation of chitosan scaffolds combined with simvastatin-loaded nanoparticles for guided bone regeneration. Chen, F; Guan, B; Jin, C; Jin, L; Li, H; Li, Y; Lin, M; Liu, D; Liu, Z; Luo, S; Song, J; Wu, M; Xue, Y; Zhang, X, 2019)	0.96
"To systematically evaluate the efficacy and safety of berberine for the treatment of hyperlipidemia, six electronic literature databases including SinoMed, CNKI, WanFang Data, PubMed, Embase and The Cochrane Library were searched to collect clinical randomized controlled trials (RCTs) of berberine alone or combined with statins for the treatment of hyperlipidemia from the inception to 8 March 2018."	( Efficacy and Safety of Berberine Alone or Combined with Statins for the Treatment of Hyperlipidemia: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. Feng, R; Ji, ZC; Jin, XY; Li, XM; Yang, FW; Zhang, BL; Zhang, JH; Zhang, LS; Zhang, MY; Zhao, MY, 2019)	0.51
" Rhabdomyolysis was most likely induced by toxic plasma concentrations of Simvastatin due to Palbociclibs inhibition of the CYP3A4 enzyme in combination with a decreased hepatic uptake of Simvastatin due to single nucleotide polymorphism rs4149056."	( Palbociclib in combination with simvastatin induce severe rhabdomyolysis: a case report. Duno, M; Hansen, K; Jeppesen, TD; Krag, T; Nersesjan, V, 2019)	1.03
" In this study, we investigated the effects of BMSC therapy in combination with simvastatin (SMV) on angiogenesis as well as on the activity of the Akt/mTOR signaling pathway during burn wound healing in rats."	( Bone Marrow-Derived Mesenchymal Stem Cells Combined With Simvastatin Accelerates Burn Wound Healing by Activation of the Akt/mTOR Pathway. Mohajer Ansari, J; Nobakht, M; Ramhormozi, P; Simorgh, S, 2020)	1.03
"The aim of this study is to observe and analyze the clinical efficacy of simvastatin combined with exercise training in the treatment of stationary chronic obstructive pulmonary disease complicated with metabolic syndrome."	( Clinical effect of simvastatin combined with exercise training in the treatment of stationary chronic obstructive pulmonary disease complicated with metabolic syndrome. Jiang, N; Liu, J; Liu, T; Luo, W, 2020)	1.12
"To evaluate the local effect of simvastatin (SVT) combined with deproteinized bovine bone (DBB) with hydroxyapatite/β-tricalcium phosphate biphasic ceramics (HA/TCP) and with collagen sponge (CS) on bone repair in critical size defects (CSDs) in rat calvaria."	( Local effect of simvastatin combined with different osteoconductive biomaterials and collagen sponge on new bone formation in critical defects in rat calvaria. Carneiro, FP; Duarte, WR; Ferreira, VMM; Oliveira, GJPL; Pinto, LNMP; Roriz, VM; Sousa, DN; Vianna, LMS, 2020)	1.19
"In the histometric analysis, the use of SVT showed to increase bone formation in the CSDs when combined with all the bone substitutes tested in this study (p<0."	( Local effect of simvastatin combined with different osteoconductive biomaterials and collagen sponge on new bone formation in critical defects in rat calvaria. Carneiro, FP; Duarte, WR; Ferreira, VMM; Oliveira, GJPL; Pinto, LNMP; Roriz, VM; Sousa, DN; Vianna, LMS, 2020)	0.9
"The use of SVT without the need for a vehicle and combined with a commercially available biomaterial may be a cheaper way to potentiate the formation of bone tissue without the need to produce new biomaterials."	( Local effect of simvastatin combined with different osteoconductive biomaterials and collagen sponge on new bone formation in critical defects in rat calvaria. Carneiro, FP; Duarte, WR; Ferreira, VMM; Oliveira, GJPL; Pinto, LNMP; Roriz, VM; Sousa, DN; Vianna, LMS, 2020)	0.9
"Self-controlled designs, specifically the case-crossover (CCO) and the self-controlled case series (SCCS), are increasingly utilized to generate real-world evidence (RWE) on drug-drug interactions (DDIs)."	( Drug-Drug Interaction Surveillance Study: Comparing Self-Controlled Designs in Five Empirical Examples in Real-World Data. Bykov, K; Gagne, JJ; Kim, S; Li, H; Lo Re, V; Vine, SM, 2021)	0.62
" The present study aimed to compare mean LDL cholesterol reduction and its variability achieved with different doses of the three statins most frequently used in monotherapy or combined with ezetimibe in a real clinical setting."	( LDL Cholesterol Reduction Variability with Different Types and Doses of Statins in Monotherapy or Combined with Ezetimibe. Results from the Spanish Arteriosclerosis Society Dyslipidaemia Registry. Bea, AM; Benaiges, D; Blanco-Vaca, F; Brea-Hernando, Á; Climent, E; Pedro-Botet, J; Perea, V; Pintó, X; Plana, N; Suárez-Tembra, M, 2022)	0.72
" As to combined treatment, the lowest and highest mean percentage LDL cholesterol reductions were obtained with simvastatin 10 mg combined with ezetimibe (50."	( LDL Cholesterol Reduction Variability with Different Types and Doses of Statins in Monotherapy or Combined with Ezetimibe. Results from the Spanish Arteriosclerosis Society Dyslipidaemia Registry. Bea, AM; Benaiges, D; Blanco-Vaca, F; Brea-Hernando, Á; Climent, E; Pedro-Botet, J; Perea, V; Pintó, X; Plana, N; Suárez-Tembra, M, 2022)	0.93
"In a real clinical setting, rosuvastatin was superior to the other statins in lowering LDL cholesterol, both as monotherapy or combined with ezetimibe."	( LDL Cholesterol Reduction Variability with Different Types and Doses of Statins in Monotherapy or Combined with Ezetimibe. Results from the Spanish Arteriosclerosis Society Dyslipidaemia Registry. Bea, AM; Benaiges, D; Blanco-Vaca, F; Brea-Hernando, Á; Climent, E; Pedro-Botet, J; Perea, V; Pintó, X; Plana, N; Suárez-Tembra, M, 2022)	0.72
"Several previous randomized controlled trials (RCTs) evaluated the efficacy of metformin combined with simvastatin in the treatment of polycystic ovary syndrome (PCOS), yet the results of the researches are not consistent."	( The efficacy and safety of metformin combined with simvastatin in the treatment of polycystic ovary syndrome: A meta-analysis and systematic review. Chen, L; Liu, Y; Shao, Y; Xie, J; Zhu, G, 2021)	1.09
"We searched PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chinese biomedical literature databases online to identify the RCTs evaluating the efficacy of metformin combined with simvastatin in the treatment of PCOS."	( The efficacy and safety of metformin combined with simvastatin in the treatment of polycystic ovary syndrome: A meta-analysis and systematic review. Chen, L; Liu, Y; Shao, Y; Xie, J; Zhu, G, 2021)	1.06
"Metformin combined with simvastatin is superior to metformin alone in the treatment of PCOS patients with more advantages in improving the levels of sex hormones, blood lipids, and blood sugar."	( The efficacy and safety of metformin combined with simvastatin in the treatment of polycystic ovary syndrome: A meta-analysis and systematic review. Chen, L; Liu, Y; Shao, Y; Xie, J; Zhu, G, 2021)	1.18
" The VEO alone and in combination with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) has significantly increased the MLN and SVN loading."	( Vitamin E Oil Incorporated Liposomal Melphalan and Simvastatin: Approach to Obtain Improved Physicochemical Characteristics of Hydrolysable Melphalan and Anticancer Activity in Combination with Simvastatin Against Multiple Myeloma. Eswara, BRM; Manjappa, AS; Nagadeepthi, N; Sambamoorthy, U; Sanapala, AK, 2021)	0.87
"This study is aimed at exploring the effects and outcomes of simvastatin combined with resistance training on the mitochondrial membrane potential (MMP) of peripheral blood lymphocytes and the Janus kinase/signal transducer and activator of the transcription 3 (JAK/STAT3) signaling pathway in patients with CHF."	( Simvastatin Combined with Resistance Training Improves Outcomes in Patients with Chronic Heart Failure by Modulating Mitochondrial Membrane Potential and the Janus Kinase/Signal Transducer and Activator of Transcription 3 Signaling Pathways. Wang, J; Wang, X; Wen, C; Yan, K, 2022)	2.41
"Simvastatin combined with resistance training improves heart function and reduces myocardial damage as well as the occurrence of adverse cardiac events compared with simvastatin alone."	( Simvastatin Combined with Resistance Training Improves Outcomes in Patients with Chronic Heart Failure by Modulating Mitochondrial Membrane Potential and the Janus Kinase/Signal Transducer and Activator of Transcription 3 Signaling Pathways. Wang, J; Wang, X; Wen, C; Yan, K, 2022)	3.61
" Both platforms predicted equally well the observed simvastatin (lactone and acid) pharmacokinetics (20-80 mg), BCRP and OATP1B1 drug-gene interactions (DGIs), and drug-drug interactions (DDIs) when co-administered with CYP3A4 and OATP1B1 inhibitors/inducers."	( Does the choice of applied physiologically-based pharmacokinetics platform matter? A case study on simvastatin disposition and drug-drug interaction. Ahlström, C; Lennernäs, H; Lundahl, A; Prieto Garcia, L; Sjögren, E; Vildhede, A, 2022)	1.19
"Methadone and buprenorphine have pharmacologic properties that are concerning for a high risk of drug-drug interactions (DDIs)."	( Identifying Clinically Relevant Drug-Drug Interactions With Methadone and Buprenorphine: A Translational Approach to Signal Detection. Acton, EK; Bilker, WB; Brensinger, CM; Dawwas, GK; Hennessy, S; Leonard, CE; Li, L; Miano, TA; Neuman, M; Nguyen, TPP; Soprano, SE; Wang, L; Woody, G; Yu, E, 2022)	0.72
" After adjusting for sociodemographic and common cardiovascular risk factors, we used multivariable logistic regression analysis to determine aspirin should be combined with which type of statin for better CVD preventive effects."	( Cardiovascular disease preventive effects of aspirin combined with different statins in the United States general population. Huangtao, Z; Li, B; Liu, T; Pan, Y; Sun, L; Wang, B; Wang, J; Wang, S; Zhu, Z; Zuo, R, 2023)	0.91
" Based on the different effects of statin members, this study aims to evaluate the effect of two of the most promising lipophilic statins, Simvastatin and Pitavastatin, and their combination with a conventional chemotherapeutic regimen of doxorubicin and cyclophosphamide on breast cancer cells."	( Enhanced therapeutic efficacy of doxorubicin/cyclophosphamide in combination with pitavastatin or simvastatin against breast cancer cells. Dewidar, SA; El Gayar, AM; El-Mesery, M; Hamdy, O; Soliman, MM, 2023)	1.33

Bioavailability

Simvastatin is poorly bioavailable as it is practically insoluble in water and shows dissolution rate-limited absorption. Only 7% of the dose reaches the general circulation intact. Chronic ingestion of high doses of the flavonol quercetin will decrease the bioavailability of simVastatin to a significant extent.

Excerpt	Reference	Relevance
" SV is well absorbed by rats, dogs, and humans."	( Metabolic disposition studies on simvastatin, a cholesterol-lowering prodrug. Chen, IW; Duggan, DE; Duncan, CA; Rosegay, A; Vickers, S, )	0.41
" The results imply a decreased bioavailability of SLS in the statin-treated group, while no evidence for an altered permeability barrier to water was found."	( Effect of systemic treatment with cholesterol-lowering drugs on the skin barrier function in humans. Agner, E; Agner, T; Malinowski, J; Meibom, J; Ramsing, D, 1995)	0.29
" Simvastatin is well absorbed from the gastrointestinal tract but is highly extracted by the liver and only 7% of the dose reaches the general circulation intact."	( Clinical pharmacokinetics and practical applications of simvastatin. Mauro, VF, 1993)	1.44
" SV undergoes an important first pass metabolism and this is thought to be partly responsible for its low bioavailability after oral administration."	( In vitro inhibition of simvastatin metabolism in rat and human liver by naringenin. Hagenbach, J; Jung, L; Koffel, JC; Ubeaud, G; Vandenschrieck, S, 1999)	0.61
"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
"Atherogenic levels of native low density lipoproteins (nLDLs) decrease the bioavailability of endothelium-derived NO and downregulate endothelial NO synthase (eNOS) expression in cultured human endothelial cells."	( 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition prevents endothelial NO synthase downregulation by atherogenic levels of native LDLs: balance between transcriptional and posttranscriptional regulation. Badimon, L; Martínez-González, J; Raposo, B; Rodríguez, C, 2001)	0.31
" Lovastatin, Atorvastatin, Pravastatin and Simvastatin demonstrate variable potency to enhance the NO/O2- concentration ratio after stimulation of NOS, resulting in an increase of NO bioavailability in endothelial cells."	( Statin-stimulated nitric oxide release from endothelium. Dobrucki, IT; Dobrucki, LW; Kalinowski, L; Malinski, T, )	0.39
"3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can exert beneficial effects independently of serum cholesterol reduction by increasing the bioavailability of nitric oxide."	( Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes. Akao, M; Jones, SP; Marbán, E; Teshima, Y, 2003)	1.76
"The main purpose of this work is to prepare self-microemulsifying drug delivery system (SMEDDS) for oral bioavailability enhancement of a poorly water soluble drug, simvastatin."	( Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Cho, SH; Chon, SK; Jeong, SY; Kang, BK; Khang, G; Lee, HB; Lee, JS; Yuk, SH, 2004)	0.73
" Extended-release niacin, also given once daily, has an absorption rate intermediate between the other formulations and is associated with fewer flushing and gastrointestinal symptoms without increasing hepatotoxic risk."	( New perspectives on the use of niacin in the treatment of lipid disorders. McKenney, J, 2004)	0.32
" Because food increases the bioavailability of fenofibrate, each dose was administered with food to maximize the exposure of fenofibric acid."	( Simvastatin does not have a clinically significant pharmacokinetic interaction with fenofibrate in humans. Bergman, AJ; Burke, J; Hartford, A; He, W; Lasseter, KC; Liu, L; Murphy, G; Paolini, JF; Prueksaritanont, T; Qiu, Y; Valesky, R; Vega, JM; Zhao, JJ, 2004)	1.77
" Dose optimization and use of novel controlled drug delivery systems may help in increasing the bioavailability and distribution of statins to the bone microenvironment."	( Statins and osteoporosis: new role for old drugs. Jadhav, SB; Jain, GK, 2006)	0.33
" In conclusion, orange juice increases the bioavailability of pravastatin administered orally."	( Orange juice increased the bioavailability of pravastatin, 3-hydroxy-3-methylglutaryl CoA reductase inhibitor, in rats and healthy human subjects. Kobayashi, S; Koitabashi, Y; Kumai, T; Matsumoto, N; Sekine, S; Watanabe, M; Yanagida, Y, 2006)	0.33
"Cyclodextrins (CDs) are cyclic oligosaccharides, capable of forming inclusion complexes with hydrophobic molecules in aqueous solution and therefore, of improving the bioavailability of many drugs."	( [Interactions in solution between cyclodextrins and statins]. Csempesz, F; Süle, A; Szente, L, 2005)	0.33
" We studied the actions of simvastatin (SIM) in enhancing NO bioavailability and reducing oxidative stress in coronary vessels from diabetic rats and in rat coronary artery endothelial cells (RCAEC) exposed to high glucose."	( Simvastatin improves diabetes-induced coronary endothelial dysfunction. Caldwell, RB; Caldwell, RW; El-Remessy, AB; Ma, G; Matragoon, S; Tawfik, HE, 2006)	2.07
" Of particular interest, statins have been shown to increase bioavailability of nitric oxide and protect against vascular inflammation and cardiac cell death in a number of cardiovascular disease states."	( Statin therapy and myocardial no-reflow. Calvert, JW; Lefer, DJ, 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
"Self-microemulsifying drug delivery systems (SMEDDS) are useful to improve the bioavailability of poorly water-soluble drugs by increasing their apparent solubility through solubilization."	( Application of mixture experimental design to simvastatin apparent solubility predictions in the microemulsifion formed by self-microemulsifying. Meng, J; Zheng, L, 2007)	0.6
"The study was designed to evaluate the effect of delayed release (DR) on absorption and bioavailability of intestinally metabolized drugs after oral dosing, using the HMG-CoA reductase inhibitor simvastatin, a CYP3A substrate, as a model drug."	( Pharmacokinetics of the CYP 3A substrate simvastatin following administration of delayed versus immediate release oral dosage forms. Amidon, GL; Hilfinger, JM; Kijek, P; Kim, JS; Langguth, P; Staubach, P; Tubic-Grozdanis, M, 2008)	0.8
"Simvastatin bioavailability was increased by a factor of three, as compared to the reference formulation Zocor."	( Pharmacokinetics of the CYP 3A substrate simvastatin following administration of delayed versus immediate release oral dosage forms. Amidon, GL; Hilfinger, JM; Kijek, P; Kim, JS; Langguth, P; Staubach, P; Tubic-Grozdanis, M, 2008)	2.05
"The interplay between gastrointestinal physiology (lower CYP 3A expression in the distal ileum and the colon) and formulation design (zero-order controlled release after a predetermined lag-time) resulted in successful absorption and bioavailability improvement and represent a viable strategy to reduce the dose of CYP 3A drugs."	( Pharmacokinetics of the CYP 3A substrate simvastatin following administration of delayed versus immediate release oral dosage forms. Amidon, GL; Hilfinger, JM; Kijek, P; Kim, JS; Langguth, P; Staubach, P; Tubic-Grozdanis, M, 2008)	0.61
"Self-nanoemulsifying granules were formulated with the objective of improving the bioavailability of the ezetimibe and simvastatin when administered together."	( Formulation and in vivo evaluation of self-nanoemulsifying granules for oral delivery of a combination of ezetimibe and simvastatin. Dixit, RP; Nagarsenker, MS, 2008)	0.76
" Enhancement of aqueous solubility, dissolution rate, and bioavailability of drug is a very challenging task in drug development."	( Co-solvent evaporation method for enhancement of solubility and dissolution rate of poorly aqueous soluble drug simvastatin: in vitro-in vivo evaluation. Gattani, S; Jain, P; Khirwal, L; Pandya, P; Surana, S, 2008)	0.56
"Melatonin was shown to reduce blood pressure, oxidative load and to increase nitric oxide bioavailability predisposing melatonin to have antiremodelling potential."	( Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats. Adamcova, M; Bednarova, K; Krajcirovicova, K; Mullerova, M; Paulis, L; Pechanova, O; Pelouch, V; Simko, F, 2009)	0.6
"Glyceryl monooleate (GMO)/poloxamer 407 cubic nanoparticles were investigated as potential oral drug delivery systems to enhance the bioavailability of the water-insoluble model drug simvastatin."	( Glyceryl monooleate/poloxamer 407 cubic nanoparticles as oral drug delivery systems: I. In vitro evaluation and enhanced oral bioavailability of the poorly water-soluble drug simvastatin. Chen, J; Hu, F; Lai, J; Lu, Y; Sun, J; Wu, W; Yin, Z, 2009)	0.74
" We conclude that chronic ingestion of high doses of the flavonol quercetin will decrease the bioavailability of simvastatin to a significant extent."	( Effects of the flavonol quercetin on the bioavailability of simvastatin in pigs. Cermak, R; Langguth, P; Wein, S; Wolffram, S, 2009)	0.81
" Previous results suggest that vascular dysfunction in OZR is associated with chronic reduction in vascular nitric-oxide (NO) bioavailability and chronic inflammation, both frequently associated with hypercholesterolemia."	( Impact of chronic anticholesterol therapy on development of microvascular rarefaction in the metabolic syndrome. Frisbee, JC; Frisbee, SJ; Goodwill, AG; James, ME; Stapleton, PA, 2009)	0.35
"While the positive impact of chronic statin treatment on vascular outcomes in the metabolic syndrome are independent of changes to total cholesterol, and are more strongly associated with improvements to vascular NO bioavailability and attenuated inflammation, these results provide both a spatial and temporal framework for targeted investigation into mechanistic determinants of vasculopathy in the metabolic syndrome."	( Impact of chronic anticholesterol therapy on development of microvascular rarefaction in the metabolic syndrome. Frisbee, JC; Frisbee, SJ; Goodwill, AG; James, ME; Stapleton, PA, 2009)	0.35
" Consequently, the absolute bioavailability (A."	( Effects of simvastatin on the pharmacokinetics of verapamil and its main metabolite, norverapamil, in rats. Choi, DH; Choi, JS; Li, C, )	0.52
"We evaluated the bioavailability of each ingredient of the Polycap and determined any drug-drug interactions relative to single component reference preparations."	( Preservation of bioavailability of ingredients and lack of drug-drug interactions in a novel five-ingredient polypill (polycap): a five-arm phase I crossover trial in healthy volunteers. Chakraborty, BS; Desai, J; Ghosh, C; Jha, V; Khamar, B; Patel, A; Shah, G; Shah, T, 2010)	0.36
"The bioavailability of the ingredients of the Polycap (T; test) when formulated as a single capsule was compared with that of identical capsules with each of its ingredients administered separately (R; reference) in a five-arm, randomized, single-dose, two-period, two-treatment, two-sequence, crossover trial with at least a 2-week washout period in a total of 195 healthy volunteers."	( Preservation of bioavailability of ingredients and lack of drug-drug interactions in a novel five-ingredient polypill (polycap): a five-arm phase I crossover trial in healthy volunteers. Chakraborty, BS; Desai, J; Ghosh, C; Jha, V; Khamar, B; Patel, A; Shah, G; Shah, T, 2010)	0.36
"Comparative bioavailability was computed and no drug-drug interactions and no difference in comparative bioavailability were concluded for each ingredient based on point estimates of the T/R ratio of the geometric means falling within 80-125% for peak plasma concentration (C(max)), area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC(t)), and AUC from time zero to infinity (AUC(infinity))."	( Preservation of bioavailability of ingredients and lack of drug-drug interactions in a novel five-ingredient polypill (polycap): a five-arm phase I crossover trial in healthy volunteers. Chakraborty, BS; Desai, J; Ghosh, C; Jha, V; Khamar, B; Patel, A; Shah, G; Shah, T, 2010)	0.36
"Simvastatin (SV), a cholesterol-lowering agent, has been widely used in the treatment of hypercholesterolemia, dyslipidemia and coronary heart disease, but SV shows the low oral bioavailability due to its poor aqueous solubility and extensive metabolism by cytochrome-3A system in intestinal guts and liver."	( The characteristics and mechanism of simvastatin loaded lipid nanoparticles to increase oral bioavailability in rats. Bu, H; Gao, F; Gao, Z; Huang, Y; Li, Y; Zhang, Z, 2010)	2.08
" Its low dissolution rate leads to a poor absorption, distribution, and target organ delivery because the bioavailability of drugs with low aqueous solubility is limited by their dissolution rates."	( Preparation and characterization of solid dispersion of simvastatin. Arantes, VT; de Oliveira, RB; Resende, JA; Silva, TD; Speziali, NL; Vianna-Soares, CD, 2010)	0.61
"The preparation of SIM SD with PEG or PVP is a promising strategy to improve the bioavailability of the drug."	( Preparation and characterization of solid dispersion of simvastatin. Arantes, VT; de Oliveira, RB; Resende, JA; Silva, TD; Speziali, NL; Vianna-Soares, CD, 2010)	0.61
"The purpose of the present investigation was to develop solid lipid nanoparticles (SLNs) of simvastatin in order to enhance its oral bioavailability by minimizing its first-pass metabolism."	( Oral solid compritol 888 ATO nanosuspension of simvastatin: optimization and biodistribution studies. Chuttani, K; Mishra, AK; Pathak, K; Shah, M, 2011)	0.85
"Statins can have beneficial cholesterol-independent effects on vascular contractility, which may involve increases in the bioavailability of NO (nitric oxide) as a result of phosphorylation of eNOS (endothelial NO synthase)."	( Acute simvastatin increases endothelial nitric oxide synthase phosphorylation via AMP-activated protein kinase and reduces contractility of isolated rat mesenteric resistance arteries. Al-Abri, M; Austin, C; Cobb, C; Rossoni, LV; Wareing, M; Wenceslau, CF, 2011)	0.85
" Consequently, the absolute bioavailability (F) of losartan after oral administration with simvastatin was significantly increased by 59."	( Effects of HMG-CoA reductase inhibitors on the pharmacokinetics of losartan and its main metabolite EXP-3174 in rats: possible role of CYP3A4 and P-gp inhibition by HMG-CoA reductase inhibitors. Choi, DH; Choi, JS; Yang, SH, 2011)	0.59
" In addition to its cholesterol-lowering effect, the ability of simvastatin to ameliorate endothelial dysfunction through increasing NO bioavailability and through suppression of oxidative stress and vascular inflammation and its ability to enhance the effect of ramipril on these parameters may play a pivotal role in these effects."	( Simvastatin enhances the antihypertensive effect of ramipril in hypertensive hypercholesterolemic animals and patients. Possible role of nitric oxide, oxidative stress, and high sensitivity C-reactive protein. Abdel-Zaher, AO; Abudahab, LH; Elbakry, MH; Elkoussi, AE; Elsayed, EA, 2012)	2.06
" The strategy of increasing the in vitro dissolution has the potential to enhance the oral bioavailability when using nanosized crystalline drugs."	( Enhanced dissolution rate and oral bioavailability of simvastatin nanocrystal prepared by sonoprecipitation. Han, N; Jiang, T; Wang, S; Xie, Y; Zhao, B, 2012)	0.63
"The aim of this article was to prepare simvastatin nanocrystals to enhance its dissolution rate and bioavailability by exploiting sonoprecipitation."	( Enhanced dissolution rate and oral bioavailability of simvastatin nanocrystal prepared by sonoprecipitation. Han, N; Jiang, T; Wang, S; Xie, Y; Zhao, B, 2012)	0.9
" Consequently, the absolute bioavailability (AB) values of diltiazem in the presence of simvastatin (1."	( Effects of simvastatin on the pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, after oral and intravenous administration in rats: possible role of P-glycoprotein and CYP3A4 inhibition by simvastatin. Choi, DH; Choi, JS; Li, C, 2011)	0.98
"The aim of this work is to improve the oral bioavailability of poorly water soluble drug, simvastatin (SV) through combining the advantages of self-nanoemulsifying systems (SNEs) and tablets."	( Self nano-emulsifying simvastatin based tablets: design and in vitro/in vivo evaluation. Abdelbary, G; Amin, M; Salah, S, )	0.67
"Due to the multi-factorial physiological implications of bariatric surgery, attempts to explain trends in oral bioavailability following bariatric surgery using singular attributes of drugs or simplified categorisations such as the biopharmaceutics classification system have been unsuccessful."	( A mechanistic pharmacokinetic model to assess modified oral drug bioavailability post bariatric surgery in morbidly obese patients: interplay between CYP3A gut wall metabolism, permeability and dissolution. Ammori, BJ; Ashcroft, DM; Darwich, AS; Jamei, M; Pade, D; Rostami-Hodjegan, A, 2012)	0.38
"The trends in oral bioavailability pre to post surgery were found to be dependent on a combination of drug parameters, including solubility, permeability and gastrointestinal metabolism as well as the surgical procedure carried out."	( A mechanistic pharmacokinetic model to assess modified oral drug bioavailability post bariatric surgery in morbidly obese patients: interplay between CYP3A gut wall metabolism, permeability and dissolution. Ammori, BJ; Ashcroft, DM; Darwich, AS; Jamei, M; Pade, D; Rostami-Hodjegan, A, 2012)	0.38
"In the absence of clinical studies, the ability to project the direction and the magnitude of changes in bioavailability of drug therapy, using evidence-based mechanistic pharmacokinetic in silico models would be of significant value in guiding prescribers to make the necessary adjustments to dosage regimens for an increasing population of patients who are undergoing bariatric surgery."	( A mechanistic pharmacokinetic model to assess modified oral drug bioavailability post bariatric surgery in morbidly obese patients: interplay between CYP3A gut wall metabolism, permeability and dissolution. Ammori, BJ; Ashcroft, DM; Darwich, AS; Jamei, M; Pade, D; Rostami-Hodjegan, A, 2012)	0.38
" About 40% of drugs are not soluble in water in practice and therefore are slowly absorbed, which results in insufficient and uneven bioavailability and GI toxicity."	( Solubility enhancement of simvastatin: a review. Murtaza, G, )	0.43
" The relative bioavailability of SIM and Simvastatin β-hydroxy acid (SIMA) for nanosuspensions layered pellets compared with commercial tablets was 117% and 173%, respectively."	( Preparation, characterization, stability and in vitro-in vivo evaluation of pellet-layered Simvastatin nanosuspensions. Feng, J; Luo, Y; Tang, X; Tao, X; Xu, L; Xu, M, 2013)	0.88
"This study investigates the potential of supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) to improve the bioavailability of poorly water-soluble drugs compared to conventional SNEDDS."	( Supersaturated self-nanoemulsifying drug delivery systems (Super-SNEDDS) enhance the bioavailability of the poorly water-soluble drug simvastatin in dogs. Garmer, M; Holm, R; Karlsson, JJ; Müllertz, A; Rades, T; Thomas, N, 2013)	0.59
" The results demonstrate that chronic ingestion of high doses of CAP will decrease the bioavailability of SV to a significant extent in rats."	( Food-drug interactions: effect of capsaicin on the pharmacokinetics of simvastatin and its active metabolite in rats. Chen, JG; Liu, JM; Lu, YN; Shi, F; Zhai, XJ, 2013)	0.62
"Low aqueous solubility is often a limiting aspect to the bioavailability of poorly soluble, but highly permeable drugs (class II compounds according to the Biopharmaceutics Classification System - BCS) administered in single drug products or as fixed dose combinations."	( New formulation approaches to improve solubility and drug release from fixed dose combinations: case examples pioglitazone/glimepiride and ezetimibe/simvastatin. Dressman, JB; Klein, S; Taupitz, T, 2013)	0.59
" Nanosized self-assembled structured liquid systems are modified microemulsions that present an alternative pathway for improving the bioavailability of poorly water-soluble drugs."	( Solubilization of simvastatin and phytosterols in a dilutable microemulsion system. Aserin, A; Fisher, S; Garti, N; Wachtel, EJ, 2013)	0.72
" Besides, its cholesterol-lowering effect, the ability of simvastatin to ameliorate endothelial dysfunction through increasing NO bioavailability and through suppression of oxidative stress and vascular inflammation may play an important role in these effects."	( Effect of simvastatin on the antihypertensive activity of losartan in hypertensive hypercholesterolemic animals and patients: role of nitric oxide, oxidative stress, and high-sensitivity C-reactive protein. Abdel-Zaher, AO; Abudahab, LH; Elbakry, MH; Elkoussi, AE; Elsayed, EA, 2014)	1.05
"Simvastatin is poorly bioavailable as it is practically insoluble in water and shows dissolution rate-limited absorption."	( Simvastatin nanoemulsion for improved oral delivery: design, characterisation, in vitro and in vivo studies. Chavhan, SS; Petkar, KC; Sawant, KK, 2013)	3.28
" Furthermore, the oral bioavailability of SIM-loaded SHMC (spherical HMC nanomatrix) in beagle dogs was compared with that of the reference formulation (Zocor®)."	( Highly ordered mesoporous carbon nanomatrix as a new approach to improve the oral absorption of the water-insoluble drug, simvastatin. Gao, C; Li, L; Li, X; Wang, H; Zhang, Y, 2013)	0.6
" Amlodipine concentrations were assumed to influence the clearance of simvastatin and simvastatin acid, which as well as the oral bioavailability was allowed to vary depending on genetic polymorphisms of metabolic enzymes."	( Development of a pharmacokinetic interaction model for co-administration of simvastatin and amlodipine. Jang, SB; Lee, D; Lim, LA; Park, K; Roh, H; Son, H, 2014)	0.87
"Simvastatin has low aqueous solubility resulting in low oral bioavailability (5%) and thus presents a challenge in formulating a suitable dosage form."	( Preparation and characterization of Simvastatin solid dispersion using skimmed milk. Banerjee, SK; Behera, AL; Gaikwad, DD; Harer, SL; Sonar, PA, 2015)	2.13
" Knockin of OATP1B1 or OATP1B3 partially restored control clearance, volume, and bioavailability values (24%-142% increase, ≤47% increase, and ≤77% decrease vs."	( Utility of Oatp1a/1b-knockout and OATP1B1/3-humanized mice in the study of OATP-mediated pharmacokinetics and tissue distribution: case studies with pravastatin, atorvastatin, simvastatin, and carboxydichlorofluorescein. Bao, JQ; Fallon, JK; Higgins, JW; Ke, AB; Manro, JR; Smith, PC; Zamek-Gliszczynski, MJ, 2014)	0.6
" Nevertheless, serious efforts are still being made to develop new SV formulations with, for example, improved tabletability or bioavailability properties."	( Thermal stability of simvastatin under different atmospheres. Bernardes, CE; Cordeiro, C; Dias, A; Diogo, HP; Minas Da Piedade, ME; Oliveira, MC; Simões, RG, 2014)	0.72
" The dissolution, contact angle and water absorption rate of these solid dispersions were measured to elucidate the relationship between wettability and dissolution."	( Understanding the relationship between wettability and dissolution of solid dispersion. Lian, R; Lu, Y; Qi, J; Tang, N; Wu, W, 2014)	0.4
" Simvastatin preserved eNOS activity and nitric oxide (NO) bioavailability during occlusion and attenuated superoxide production following reperfusion."	( The effect of acute simvastatin administration on the severity of arrhythmias resulting from ischaemia and reperfusion in the canine: Is there a role for nitric oxide? Gardi, J; Kaszaki, J; Kisvári, G; Kovács, M; Seprényi, G; Végh, Á, 2014)	1.64
" The present study was undertaken to investigate the effect of VD supplementation on the bioavailability and lipid lowering effect of simvastatin (ST)."	( Effect of vitamin D on bioavailability and lipid lowering efficacy of simvastatin. Al-Asmari, AK; Al-Eid, A; Al-Omani, SF; Al-Sabaan, F; Tariq, M; Ullah, Z, 2015)	0.85
"The aim of this study was to obtain a stable, amorphous solid dispersion (SD) with Soluplus, prepared by hot-melt extrusion (HME) as an effective and stable oral delivery system to improve the physical stability and bioavailability of the poorly water-soluble simvastatin (SIM), a drug with relatively low Tg."	( Extruded Soluplus/SIM as an oral delivery system: characterization, interactions, in vitro and in vivo evaluations. Liu, Y; Luo, Y; Tang, X; Tian, B; Yao, Q; Zhang, Y; Zhong, Y, 2016)	0.61
" However, green tea may interfere with the oral bioavailability or activity of cardiovascular drugs by various mechanisms, potentially leading to reduced drug efficacy or increased drug toxicity."	( Overview of green tea interaction with cardiovascular drugs. Adachi, E; Cavalca, V; Giroli, MG; Inui, N; Kawabe, K; Laguzzi, F; Misaka, S; Myasoedova, V; Onoue, S; Squellerio, I; Takeuchi, K; Tremoli, E; Veglia, F; Watanabe, H; Werba, JP; Yamada, S, 2015)	0.42
"New drug formulations are sought for poorly water-soluble substances because there is a risk of compromised bioavailability if such substances are administered orally."	( Structural insight into the physical stability of amorphous Simvastatin dispersed in pHPMA: enhanced dynamics and local clustering as evidenced by solid-state NMR and Raman spectroscopy. Brus, J; Kredatusova, J; Sturcova, A; Urbanova, M, 2015)	0.66
" In vivo pharmacokinetics in rats showed an increase in bioavailability of micronised simvastatin (3."	( Micronisation of simvastatin by the supercritical antisolvent technique: in vitro-in vivo evaluation. Patel, JK; Sutariya, VB, 2015)	0.98
" Bioavailability estimation in rats revealed an augmentation in SMV bioavailability from the optimized SMV-zein formulation, by fourfold relative to SMV suspension."	( Optimization of caseinate-coated simvastatin-zein nanoparticles: improved bioavailability and modified release characteristics. Ahmed, OA; Al-Sawahli, MM; Fahmy, UA; Hosny, KM, 2015)	0.7
"An early prediction of solubility in physiological media (PBS, SGF and SIF) is useful to predict qualitatively bioavailability and absorption of lead candidates."	( Thermodynamic equilibrium solubility measurements in simulated fluids by 96-well plate method in early drug discovery. Bharate, SS; Vishwakarma, RA, 2015)	0.42
"This study compared formulation effects of a dendrimer and a liposome preparation on the water solubility, transepithelial transport, and oral bioavailability of simvastatin (SMV)."	( G5 PAMAM dendrimer versus liposome: a comparison study on the in vitro transepithelial transport and in vivo oral absorption of simvastatin. Banaszak Holl, MM; Cao, Y; Chen, C; He, B; Liu, G; Qi, R; Shen, W; van Dongen, MA; Wang, C; Wang, S; Wang, Y; Xu, L; Zhang, H; Zhang, Q, 2015)	0.82
" In this study, the authors compared G5 PAMAM dendrimers to liposome preparations in terms of solubility, transepithelial transport, and oral bioavailability of this poorly water-soluble drug."	( G5 PAMAM dendrimer versus liposome: a comparison study on the in vitro transepithelial transport and in vivo oral absorption of simvastatin. Banaszak Holl, MM; Cao, Y; Chen, C; He, B; Liu, G; Qi, R; Shen, W; van Dongen, MA; Wang, C; Wang, S; Wang, Y; Xu, L; Zhang, H; Zhang, Q, 2015)	0.62
" However, taken orally, their bioavailability is low to the bones."	( Single-dose local simvastatin injection improves implant fixation via increased angiogenesis and bone formation in an ovariectomized rat model. Cui, Y; Fu, X; Guo, Q; Leng, H; Ma, T; Song, C; Tan, J; Yang, N; Yin, X, 2015)	0.75
" Studies have found that simvastatin stimulates bone formation, but the skeletal bioavailability of orally administered is low."	( A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs. Cui, YY; Du, GH; Fu, X; Guo, Q; Leng, HJ; Liu, C; Liu, ZJ; Ma, T; Song, CL; Sun, CG; Tan, J; Wang, H; Xu, YS; Yin, X; Zhang, XH, 2016)	0.97
" Pharmacokinetic evaluation in rabbits indicated higher AUC for the formulation with highest content of thiomer and level 'A' correlation could be established from the generated dissolution and bioavailability data."	( Formulation of mucoadhesive gastric retentive drug delivery using thiolated xyloglucan. Bargaje, RV; Bhalekar, MR; Kshirsagar, SJ; Madgulkar, AR; Upadhaya, PG, 2016)	0.43
" Moreover, neutral liposomes exhibited higher bioavailability in plasma 4 hours after being administered."	( Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats. Campos-Martorell, M; Cano-Sarabia, M; Hernández-Guillamon, M; Maspoch, D; Montaner, J; Rosell, A; Simats, A, 2016)	0.68
" Thus, simvastatin encapsulation might be a promising strategy to ensure that the drug reaches the brain, while increasing its bioavailability and reducing possible side effects."	( Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats. Campos-Martorell, M; Cano-Sarabia, M; Hernández-Guillamon, M; Maspoch, D; Montaner, J; Rosell, A; Simats, A, 2016)	1.13
" The aim of this study is to use a simple, fast, and nondestructive near-infrared transmission spectroscopic method to quantify simvastatin (SMV) concentrations in mice plasma and also to improve SMV bioavailability by using alpha-lipoic acid as a carrier."	( Quantification of simvastatin in mice plasma by near-infrared and chemometric analysis of spectral data. Fahmy, UA, 2016)	0.97
" The results of biological studies revealed that administration of SV loaded NLCs to rats increased SV bioavailability compared to SV suspension."	( Simvastatin-loaded nanostructured lipid carriers attenuate the atherogenic risk of erythrocytes in hyperlipidemic rats. Alomrani, AH; Badran, MM; Harisa, GI, 2017)	1.9
" Statins have been found to stimulate bone formation, but the bioavailability from oral administration is low."	( Intraosseous Injection of Simvastatin in Poloxamer 407 Hydrogel Improves Pedicle-Screw Fixation in Ovariectomized Minipigs. Fu, X; Leng, HJ; Song, CL; Sun, CG; Tan, J; Xu, YS, 2016)	0.73
" Impaired bioavailability of endothelial nitric oxide synthase (eNOS) is one of the main reasons of endothelial dysfunction."	( mZD7349 peptide-conjugated PLGA nanoparticles directed against VCAM-1 for targeted delivery of simvastatin to restore dysfunctional HUVECs. Amani, A; Deiham, B; Doosti, M; Faramarzi, MA; Imanparast, F; Kobarfard, F; Paknejad, M; Vatannejad, A, 2017)	0.67
"Categorized as a Biopharmaceutics Classification System (BCS) Class II drugs, statin exhibit low aqueous solubility and bioavailability thus presenting an obstacle and great challenge to formulation researchers."	( Arginine Complexes with Simvastatin: Apparent Solubility, In Vitro Dissolution and Solid State Characterization. Affandi, MMRMM; Majeed, ABA; Tripathy, M, 2018)	0.79
"Abolition of diazepam anxiolytic effect during concomitant use of simvastatin is probably caused by diminished bioavailability of diazepam, although pharmacodynamic interaction between these drugs cannot be excluded."	( Pharmacodynamic and pharmacokinetic interactions between simvastatin and diazepam in rats. Rutkowska, M; Słupski, W; Trocha, M, 2017)	0.94
"In the context of the global prevalence of vitamin D insufficiency, we compared two key determinants of the bioavailability of 3 vitamin D forms with significant biopotencies: cholecalciferol, 25-hydroxycholecalciferol and 1-α-hydroxycholecalciferol."	( Comparison of the Micellar Incorporation and the Intestinal Cell Uptake of Cholecalciferol, 25-Hydroxycholecalciferol and 1-α-Hydroxycholecalciferol. Borel, P; Desmarchelier, C; Margier, M; Nowicki, M; Prévéraud, DP; Reboul, E; Rosilio, V, 2017)	0.46
"The purpose of the current study is to develop nanostructured lipid carriers (NLCs) for the delivery of the antihyperlipidemic drug simvastatin (SIM) to increase its extremely low oral bioavailability (<5%) and prolong its antihyperlipidemic effect."	( Nanostructured lipid carriers for improved oral delivery and prolonged antihyperlipidemic effect of simvastatin. Allam, A; El-Badry, M; Elsabahy, M; Fathi, HA; Fetih, G, 2018)	0.9
"In comparison to other published results, this study considered the extensive pre-systemic clearance of SV, which could significantly decrease its systemic and hepatic bioavailability if SV is delivered into the small intestine."	( In vitro/in silico approach in the development of simvastatin-loaded self-microemulsifying drug delivery systems. Ćetković, Z; Cvijić, S; Vasiljević, D, 2018)	0.73
"The obtained results suggested that combined strategy for the improvement of SV bioavailability should comprise solubility enhancement and delayed drug release."	( In vitro/in silico approach in the development of simvastatin-loaded self-microemulsifying drug delivery systems. Ćetković, Z; Cvijić, S; Vasiljević, D, 2018)	0.73
" However, oral (PO) administration of berberine is hindered by poor bioavailability and increasing dose often elicits gastro-intestinal side effects."	( Comparative pharmacokinetics and safety assessment of transdermal berberine and dihydroberberine. Azike, CG; Baranowski, DC; Buchanan, B; Gabriele, J; Meng, Q; Poulin, MM; Zuccolo, J, 2018)	0.48
"Simvastatin is poorly bioavailable because it is practically insoluble in water and shows dissolution rate-limited absorption."	( Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats. Fan, H; Gu, F; Ning, J; Wang, Y; Wu, C, 2018)	2.2
" However, SIM has low bioavailability and may induce the upregulation of the BMP-2-antagonistic noggin protein, which greatly limits the osteogenic effect."	( pH-Sensitive Nanocarrier-Mediated Codelivery of Simvastatin and Noggin siRNA for Synergistic Enhancement of Osteogenesis. Chen, B; Cheng, D; Deng, S; Fang, J; Feng, X; Huang, J; Li, X; Lin, C; Shuai, X; Su, W; Wang, J; Zhang, S, 2018)	0.74
" In the preliminary formulation development phase 1-oleoyl-rac-glycerol was chosen as the oily lipid phase, based on the high drug solubility and potential bioavailability enhancement capability."	( A redispersible dry emulsion system with simvastatin prepared via fluid bed layering as a means of dissolution enhancement of a lipophilic drug. Dreu, R; Luštrik, M; Pirker, L; Pohlen, M, 2018)	0.75
" The PLGA-based hybrid nanocarrier system has been designed in such a way to evade the low bioavailability of SMV, confer sustained release of both encapsulated and chemically conjugated SMV, as well as enhancing the anti-cancer effect of the formula via the magnetic targeting with the aid of the encapsulated SPIONS."	( Hybrid nanocarrier system for guiding and augmenting simvastatin cytotoxic activity against prostate cancer. El-Sherbiny, IM; Khalil, IA; Sedki, M, 2018)	0.73
"The purpose of the study was formulation development, optimization and evaluation of a Self-Emulsifying Drug Delivery System (SEDDS) of Simvastatin (SIM) for improvement in dissolution and bioavailability of SIM."	( Self-Emulsifying Drug Delivery System of Simvastatin: Formulation Development, Optimization by Box- Behnken Design, Kumar, Y; Nanda, A; Verma, M, 2018)	0.95
"Pharmacokinetic analyses revealed an increase in the bioavailability of simvastatin when co-administered with amlodipine [Nishio S et al."	( Analysis of secondary care data to evaluate the clinical relevance of the drug-drug interaction between amlodipine and simvastatin. Fuhrmann, S; Knoth, H; Koppen, A; Schröder, J; Seeling, A, 2019)	0.95
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."	( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)	0.51
"Silica-lipid hybrid (SLH) microparticles are a solidified lipid-based drug delivery system under investigation for their aptitude to enhance the oral bioavailability of poorly water-soluble drugs."	( Enhancing the oral bioavailability of simvastatin with silica-lipid hybrid particles: The effect of supersaturation and silica geometry. Meola, TR; Peressin, KF; Prestidge, CA; Schultz, HB, 2020)	0.83
"Simvastatin (SMV), a hypocholesterolemic agent, suffers from very low bioavailability due to its poor aqueous solubility and extensive first-pass metabolism."	( Enhancement of Simvastatin ex vivo Permeation from Mucoadhesive Buccal Films Loaded with Dual Drug Release Carriers. Ahmed, TA; Alharbi, WS; Bawazir, AO; Safo, MK, 2020)	2.35
"This study aimed to enhance the dissolution of simvastatin (SMV) through its formulation in liquisolid tablets (LSTs) to improve its bioavailability and hypolipidemic activity after oral administration."	( Enhancing the Hypolipidemic Effect of Simvastatin in Poloxamer-Induced Hyperlipidemic Rats via Liquisolid Approach: Pharmacokinetic and Pharmacodynamic Evaluation. Ahmed, OAA; Ahmed, TA; El-Say, KM; Elimam, H, 2020)	1.09
" However, due to its poor intrinsic water solubility, the drug is poorly absorbed from the gastrointestinal tract and exhibits a low oral bioavailability of approximately 5%."	( A safety, tolerability, and pharmacokinetic study of a novel simvastatin silica-lipid hybrid formulation in healthy male participants. Abuhelwa, AY; Clifton, P; Joyce, P; Meola, TR; Prestidge, CA, 2021)	0.86
"Co-crystallization with NIC improved the solubility and dissolution profile and, hence, the bioavailability of the poorly water-soluble drug SIM."	( Simvastatin-Nicotinamide Co-Crystals: Formation, Pharmaceutical Characterization and in vivo Profile. Ahmad, M; Idrees, HA; Khan, FM, 2020)	2
"Because of the low solubility, the oral bioavailability of simvastatin (SV) was poor, which restricted the application in clinic."	( A promising nanomatrix system of simvastatin for oral delivery: Evaluation in vitro and in vivo. Cui, Z; Duan, L; He, S; Li, Y; Zhang, X, 2020)	1.08
" Delivery of simvastatin in the form of an inclusion complex with HPβCD is proposed as an approach improving its bioavailability in the cholesterol-lowering therapies."	( Incorporation of simvastatin into lipid membranes: Why deliver a statin in form of inclusion complex with hydrophilic cyclodextrin. Bartkowiak, A; Bilewicz, R; Broniatowski, M; Krzak, A; Matyszewska, D; Zaborowska, M, 2021)	1.33
"Although simvastatin (SIM) has been proven to be a powerful agent against myocardial ischemia/reperfusion (MI/R) injury, poor water solubility, short half-life, and low bioavailability have made it futile while using conventional drug delivery system."	( Simvastatin-loaded nano-niosomes confer cardioprotection against myocardial ischemia/reperfusion injury. Aboutaleb, N; Akbarzade, I; Naseroleslami, M; Niri, NM; Sharifi, M, 2022)	2.58
" Thus, these biocompatible nanoparticles have the potential to bypass poor CoQ oral bioavailability as a treatment option for individuals with severe CoQ deficiency syndromes and/or aging-related CoQ depletion."	( Coenzyme Q nanodisks counteract the effect of statins on C2C12 myotubes. Dagda, RK; Moschetti, A; Ryan, RO, 2021)	0.62
" The pleiotropic effects of statins have been well described in many in vitro and in vivo studies, but these effects are difficult to achieve in clinical practice due to the low bioavailability of statins and their first-pass metabolism in the liver."	( Anti-Inflammatory Effect of Very High Dose Local Vessel Wall Statin Administration: Poly(L,L-Lactide) Biodegradable Microspheres with Simvastatin for Drug Delivery System (DDS). Basinska, T; Czuczwar, S; Dabrowski, W; Gadzinowski, M; Kocki, J; Oru, N; Slomkowski, S; Szumilo, J; Vicaut, E; Wacinski, J; Wacinski, P, 2021)	0.82
" Among the two technologies, fluid bed layering provided dry emulsion products with higher relative bioavailability and better product characteristics for further processing into final dosage forms."	( Relative bioavailability enhancement of simvastatin via dry emulsion systems: Comparison of spray drying and fluid bed layering technology. Aguiar Zdovc, J; Dreu, R; Gosenca Matjaž, M; Grabnar, I; Mravljak, J; Pohlen, M; Snoj, T; Trontelj, J, 2022)	0.99
" Due to low bioavailability and short half-life of simvastatin, liposomal NPs have the potential to enhance drug delivery, however, in this study NP did not provide improvement over simvastatin, but did demonstrate their potential for the delivery of simvastatin."	( Simvastatin-loaded liposome nanoparticles treatment for uterine leiomyoma in a patient-derived xenograft mouse model: a pilot study. Afrin, S; Borahay, MA; El Sabeh, M; Kilic, GS; Motamedi, M; Ozpolat, B; Saada, J; Vincent, KL; Yang, J, 2022)	2.42
" Among NS and SNEDDS, NS was found more efficacious than that of the SNEDDS possibly due to higher enhancement of oral bioavailability in case of NS."	( Expanding arsenal against diabetes mellitus through nanoformulations loaded with glimepiride and simvastatin: A comparative study. Chellappan, DK; Dua, K; Dureja, H; Gulati, M; Gupta, G; Gupta, PK; Gupta, S; Jha, NK; Jha, SK; Khursheed, R; Kumar, B; Pandey, NK; Prasher, P; Sharma, A; Singh, SK; Vishwas, S, 2022)	0.94
" However, the low bioavailability of oral statin formulations is a key barrier to achieving effective doses within tumour."	( Formulation of simvastatin within high density lipoprotein enables potent tumour radiosensitisation. Badiee, P; Berbeco, RI; Cheah, E; Dehghankelishadi, P; Dmochowska, N; Kempson, I; Maritz, MF; Thierry, B, 2022)	1.07
"Self-emulsifying drug-delivery systems (SEDDSs) are designed to improve the oral bioavailability of poorly water-soluble drugs."	( Development and Evaluation of Self-Emulsifying Drug-Delivery System-Based Tablets for Simvastatin, a BCS Class II Drug. Abbas, M; Bashir, MA; Goh, KW; Khan, A; Khuda, F; Ming, LC; Shah, SI; Ullah, M, 2023)	1.13
"Using commonly available excipients and machinery, SEDDS-based tablets with better dissolution profile and bioavailability can be prepared by direct compression."	( Development and Evaluation of Self-Emulsifying Drug-Delivery System-Based Tablets for Simvastatin, a BCS Class II Drug. Abbas, M; Bashir, MA; Goh, KW; Khan, A; Khuda, F; Ming, LC; Shah, SI; Ullah, M, 2023)	1.13

Dosage Studied

Simvastatin was administered at a dosage of 5 mg/day for 24 weeks to 38 HD patients with high serum total cholesterol (TC) levels (200 mg/dl) or low high-density lipoprotein choles. In rat liver slices, the dose-response curves for inhibition of [14C]acetate incorporation into cholesterol were similar for the active acid forms of lovastatin, simvstatin, and pravastatin.

Excerpt	Relevance	Reference
"Subjects were randomly assigned to receive either colestipol placebo or colestipol 5 g or 10 g each morning in fixed dosage for 18 weeks."	( Successful management of primary hypercholesterolaemia with simvastatin and low-dose colestipol. Parfitt, A; Simons, J; Simons, LA, 1992)	0.53
" Such combination therapy offers the possibility of improved cholesterol lowering without the need for full dosage of either drug."	( Successful management of primary hypercholesterolaemia with simvastatin and low-dose colestipol. Parfitt, A; Simons, J; Simons, LA, 1992)	0.53
" Various dosing regimens of 10, 20, and 40 mg/day were employed."	( Efficacy and tolerability of medium-term treatment with simvastatin in primary hypercholesterolaemia. Cattaneo, R; Colombo, F; Geroli, L; Marnini, P; Venco, A, 1992)	0.53
"The effects of age and of gender on the plasma profiles of HMG-CoA reductase inhibitors following separate once-a-day dosage regimens (17 days) of lovastatin (80 mg/day) and simvastatin (40 mg/day) were studied in hypercholesterolemic patients."	( Influence of age and gender on the plasma profiles of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitory activity following multiple doses of lovastatin and simvastatin. Amin, RD; Cheng, H; Dobrinska, MR; Quan, H; Rogers, JD; Stein, EA; Sweany, AE; Tate, AC, 1992)	0.67
" The mean dosage of the simvastatin at fourth month was of 25 mg/die."	( [Mid-term clinical study of the effectiveness of and tolerability to simvastatin ++ in dyslipidemic patients]. Aiello, C; De Lucia, R; Dragonetti, C; Irace, L; Papa, A; Petraglia, L; Sannino, A, 1992)	0.83
" The subjects selected for the study were suffering from uremia either complied with dosage prescribed or not."	( [Dyslipidemia in the uremic patient: the therapeutic role played by simvastatin]. Angelé, B; Bellinghieri, G; Savica, V, 1992)	0.52
" This original design allowed to define the most appropriate individual cholesterol-lowering drug dosage in FH patients."	( Lecithin: cholesterol acyltransferase activity in familial hypercholesterolemia treated with simvastatin and simvastatin plus low-dose colestipol. Desager, JP; Harvengt, C; Horsmans, Y, 1991)	0.5
" Adequate precision was obtained to reliably verify drug dosage levels."	( Rapid verification of identity and content of drug formulations using mid-infrared spectroscopy. Brooks, MA; Compton, DA; Compton, SV; Ryan, JA, 1991)	0.28
"The effects of long-term dosing with inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase on the rate of cholesterol biosynthesis were examined in the lens and liver of rats and hamsters."	( Effects of long-term administration of HMG-CoA reductase inhibitors on cholesterol synthesis in lens. Kalinowski, SS; Mosley, ST; Tanaka, RD, 1991)	0.28
"An extended-release osmotic dosage form was designed for gastrointestinal delivery of the water-soluble tromethamine salt of the beta-hydroxyacid form of simvastatin, a potent HMG-CoA reductase inhibitor and cholesterol lowering agent."	( Enhancement of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor efficacy through administration of a controlled-porosity osmotic pump dosage form. Fix, JA; McClelland, GA; Pogany, SA; Stubbs, RJ; Zentner, GM, 1991)	0.48
" Twenty-seven Japanese white rabbits were divided according to dosage of simvastatin into four groups as follows, group P (placebo, 5 rabbits), group MK 1 (simvastatin 1mg/kg, 5 rabbits), group MK 3 (simvastatin 3mg/kg, 6 rabbits) and group MK 5 (simvastatin 5mg/kg, 5 rabbits)."	( [Preventive effect of simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on coronary atherosclerosis in cholesterol-fed rabbits]. Oogushi, K, 1991)	0.83
" Patients were treated with progressively increasing doses of simvastatin (20, 40, and 80 mg day-1) taken in a twice-daily dosage for a period of 6 weeks on each dose."	( The effects of simvastatin on plasma lipoproteins and cholesterol homeostasis in patients with heterozygous familial hypercholesterolaemia. Hagemenas, FC; Illingworth, DR; Pappu, AS, 1990)	0.87
" Bezafibrate was administered as a 200 mg dose 3 times daily, while simvastatin dosage ranged from 10 mg to 40 mg once daily at night."	( Bezafibrate and simvastatin (MK-733) in the treatment of primary hypercholesterolaemia. Jankelow, D; Myburgh, DP; Neutel, JM; Smith, DH, 1990)	0.86
" The initial dosage of simvastatin was 10 mg/day; dosage was titrated up to 10 mg/day or to a minimum of 5 mg/day in intervals of at least 4 weeks, in order to maintain LDL-cholesterol below 140 mg/dl."	( [Simvastatin (MK-733), a new HMG-CoA reductase inhibitor, in the treatment of hypercholesterolemia in elderly patients with atherosclerosis]. de Góes, JM; Dereviack, BE; Diament, J; Forti, N; Giannini, SD; Machado, C, 1990)	1.5
" Analysis of lenses from dogs chronically dosed with various HMG-CoA reductase inhibitors revealed the presence of low drug levels in the lens (less than 500 ng equivalents g-1), but no correlation was observed between the amount of drug associated with the lens after chronic treatment and cataract development."	( On the etiology of subcapsular lenticular opacities produced in dogs receiving HMG-CoA reductase inhibitors. Alberts, AW; Bokelman, DL; Chen, J; Gerson, RJ; Greenspan, MD; MacDonald, JS; Rubin, LF; Yudkovitz, JB, 1990)	0.28
" Our phase I results were commensurate with those reported for the entire international cohort of 272 patients, indicating a clear dose-response relationship, with approximately 75% of the maximum reduction in LDL-C levels being achieved with 20 mg/day and over 90% of the maximum being achieved with 40 mg of simvastatin per day."	( Treatment of hypercholesterolemia with the HMG CoA reductase inhibitor, simvastatin. Baker, SG; Berger, GM; Joffe, BI; Marais, AD; Mendelsohn, D; Seftel, HC; Welsh, NH, 1989)	0.68
" In rat liver slices, the dose-response curves for inhibition of [14C]acetate incorporation into cholesterol were similar for the active acid forms of lovastatin, simvastatin, and pravastatin."	( Tissue-selective acute effects of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase on cholesterol biosynthesis in lens. Kalinowski, SS; Mosley, ST; Schafer, BL; Tanaka, RD, 1989)	0.47
" The initial dosage of simvastatin was a tablet of 10 mg/day, increased after a month to 20 mg and then to 40 mg/die."	( [Effect of a long-term treatment with simvastatin, an inhibitor of HMG-CoA reductase, in dyslipidemic patients at high risk]. Abrignani, MG; Alaimo, G; Averna, MR; Barbagallo, CM; Davì, G; Marino, G; Notarbartolo, A; Novo, S; Strano, A, 1989)	0.86
" Many of the toxicities produced by high dosage levels of simvastatin in animals are directly related to the drug's biochemical mechanism of action and are the result of a profound, sustained inhibition of the target enzyme that is not anticipated at clinical dosages."	( Animal safety and toxicology of simvastatin and related hydroxy-methylglutaryl-coenzyme A reductase inhibitors. Alberts, AW; Bokelman, DL; Gerson, RJ; Kornbrust, DJ; MacDonald, JS; Majka, JA; Stubbs, RJ, 1989)	0.8
" Gemfibrozil was given in a constant dosage of 600 mg twice daily in both strata."	( Comparison of low-dose simvastatin and gemfibrozil in the treatment of elevated plasma cholesterol. A multicenter study. The Simvastatin Study Group. Bocanegra, TS; Cook, T; Tikkanen, MJ; Walker, JF, 1989)	0.59
" Simvastatin at the dosage of 10 mg appeared to be at least as efficient as 12 g of cholestyramine and generally better tolerated."	( Comparison between low-dose simvastatin and cholestyramine in moderately severe hypercholesterolemia. Deslypere, JP, 1989)	1.48
" In the range of dosage from 10 to 40 mg once daily, therapy is associated with reductions of up to 30 percent in total cholesterol and 40 percent in low-density lipoprotein cholesterol levels, as well as with increases of approximately 10 percent in high-density lipoprotein cholesterol levels."	( Simvastatin: the clinical profile. Walker, JF, 1989)	1.72
" This difference is consistent throughout the dosage range."	( Pharmaco-economic assessment of the HMG-CoA reductase inhibitors. Smart, AJ; Walters, L, 1994)	0.29
"8% higher than an equivalent milligram dose of pravastatin, depending on the dosage used."	( Pharmaco-economic assessment of the HMG-CoA reductase inhibitors. Smart, AJ; Walters, L, 1994)	0.29
" Severe renal insufficiency may necessitate dosage modification in lovastatin recipients."	( Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Garnett, WR, 1995)	0.29
" Dose-response curves for serotonin-induced vasodilatation, an index of nitric oxide-dependent vasodilatation, showed a comparable and significant rightward shift after a medication-free period of 2 and 6 weeks compared with control subjects, indicating endothelial dysfunction, which was already maximum after 2 weeks."	( Vascular function in the forearm of hypercholesterolaemic patients off and on lipid-lowering medication. de Bruin, TW; Koomans, HA; Rabelink, TJ; Stroes, ES, 1995)	0.29
" The drugs were administered in dosages of 10 mg/kg from the fourth to seventh weeks; at the end of the seventh week, plasma cholesterol was determined, and the Pravastatin dosage adjusted to 15 mg/kg to obtain similar levels of plasma cholesterol for the two experimental groups."	( Effects of simvastatin and pravastatin on endothelium-dependent relaxation in hypercholesterolemic rabbits. Jorge, PA; Metze, K; Ozaki, MR, 1994)	0.68
" Micronized fenofibrate, a new formulation chemically identical to the parent compound, has improved pharmacokinetic parameters which increase absorption, provide more stable plasma levels, and thus dosage can be decreased."	( The fibrates in clinical practice: focus on micronised fenofibrate. Shepherd, J, 1994)	0.29
" Fourteen subjects were given simvastatin, and 12 were given pravastatin, both at the maximum therapeutic dosage of 40 mg/day."	( Sustained therapy with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors does not impair steroidogenesis by adrenals and gonads. Faccini, G; Moghetti, P; Muggeo, M; Negri, C; Tosi, F; Travia, D, 1995)	0.58
" Simvastatin should be administered in a reduced dosage to CS patients."	( Plasma concentration profiles of simvastatin 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin. Arnadottir, M; Eriksson, LO; Karkas, JD; Thysell, H, 1993)	1.48
"Seven sustained/controlled-release dosage forms were designed for gastrointestinal delivery of lovastatin or simvastatin, two potent HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia."	( Evaluation of sustained/controlled-release dosage forms of 3-hydroxy-3-methylglutaryl-coenzyme a (HMG-CoA) reductase inhibitors in dogs and humans. Amin, RD; Cheng, H; Grasing, K; Mitchel, YB; Pipkin, JD; Rogers, JD; Schwartz, JI; Schwartz, MS; Sutton, SC; Zentner, GM, 1993)	0.5
"Using various concentrations of the drugs, a dose-response curve was constructed for the inhibition of the cholesterol synthesis."	( Pravastatin and simvastatin differently inhibit cholesterol biosynthesis in human lens. Bloemendal, H; Cohen, LH; de Vries, AC; Vermeer, MA, 1993)	0.63
"The efficacy and safety profile of simvastatin and pravastatin across their most commonly recommended dosage ranges were compared in a double-blind, parallel, multicenter study in 550 patients with primary hypercholesterolemia."	( Comparison of the efficacy, safety and tolerability of simvastatin and pravastatin for hypercholesterolemia. The Simvastatin Pravastatin Study Group. , 1993)	0.81
" In posttransplant patients receiving cyclosporine, safety has been documented for low doses of lovastatin and simvastatin, but when a higher dosage of an HMG-CoA reductase inhibitor is warranted, pravastatin should be considered the drug of choice because of a lower incidence of myopathy."	( Comparative evaluation of the safety and efficacy of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. Hsu, I; Johnson, NE; Spinler, SA, )	0.34
" Reductions in serum levels of total cholesterol and LDL-cholesterol were similar between agents only when lovastatin or pravastatin were administered at a total daily dosage twice that of simvastatin and when fluvastatin was administered at a total daily dosage approximately 8 times that of simvastatin."	( Simvastatin. A reappraisal of its pharmacology and therapeutic efficacy in hypercholesterolaemia. McTavish, D; Plosker, GL, 1995)	1.92
" It is likely that the magnitude of risk reduction produced by lipid-lowering therapy is proportional to the degree of cholesterol lowering achieved, which is an important consideration when selecting an agent and deciding the dosage to use."	( Benefits and risks of HMG-CoA reductase inhibitors in the prevention of coronary heart disease: a reappraisal. Pedersen, TR; Tobert, JA, 1996)	0.29
" A metaanalysis of ten trials has shown a 25% decrease in vascular events in the long-term, irrespective of age, gender, blood pressure blood glucose level, and dosage whether low (75 to 160 mg) or moderate (160 to 325 mg/day)."	( [Secondary prevention after myocardial infarction; rôle of platelet antiaggregants and hypolipemic agents]. Aumont, MC; Seknadji, P, 1996)	0.29
" To evaluate the effectiveness of extending the dosage range, 156 subjects with LDL cholesterol >160 mg/dl and triglycerides (TG) <350 mg/dl were randomized to simvastatin at doses of 40, 80, and 160 mg/day in a 26 week, double-blind, 3-period, complete block crossover study."	( The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day. Amin, RD; Davidson, MH; Dobrinska, MR; Dujovne, CA; Hunninghake, DB; Illingworth, DR; Knopp, RH; Melino, MR; Mitchel, YB; Stein, EA; Tobert, JA; Weiss, SR; Zupkis, RV, 1997)	0.76
" Participants in the 4S were randomly assigned to double-blind treatment with simvastatin, 20 mg daily, with blinded dosage titration up to 40 mg daily, according to cholesterol response during the first 6-18 weeks, or placebo."	( Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S) Faergeman, O; Kjekshus, J; Olsson, AG; Pedersen, TR; Pyŏrälä, K; Thorgeirsson, G, 1997)	0.83
"52 mmol/L (400 mg/dl) received once-daily dosing with atorvastatin (Lipitor) 10 mg or simvastatin (Zocor) 10 mg."	( A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia. Best, J; Black, D; Bracs, P; d'Emden, M; Dart, A; Hamilton-Craig, I; Jerums, G; Nicholson, G; Sullivan, D; Tallis, G; West, M, 1997)	0.74
" The dosage consisted of 10 mg simvastatin daily during the 3-month trial."	( Short-term safety and efficacy of low-dose simvastatin in elderly patients with hypertensive hypercholesterolemia and fasting hyperinsulinemia. Chan, P; Huang, TY; Lee, C; Lee, YS; Tomlinson, B, 1997)	0.85
" Micronised fenofibrate has improved absorption characteristics compared with the standard preparation, allowing a lower daily dosage and once-daily administration."	( Micronised fenofibrate: a review of its pharmacodynamic properties and clinical efficacy in the management of dyslipidaemia. Adkins, JC; Faulds, D, 1997)	0.3
"To investigate the effects of lipid lowering therapy on the fraction unbound and dosage requirement of cyclosporine in heart transplant recipients."	( Effect of simvastatin on cyclosporine unbound fraction and apparent blood clearance in heart transplant recipients. Akhlaghi, F; Brown, KF; Keogh, AM; McLachlan, AJ, 1997)	0.7
" Cyclosporine daily dosage and total concentration (monoclonal FPIA method) were recorded for periods up to 6 months before and after simvastatin administration."	( Effect of simvastatin on cyclosporine unbound fraction and apparent blood clearance in heart transplant recipients. Akhlaghi, F; Brown, KF; Keogh, AM; McLachlan, AJ, 1997)	0.9
" The two drugs exhibited similar IC50's for inhibition of either rat or human reductase, and single oral dosing in rats showed the compounds to be nearly equipotent at inhibiting hepatic cholesterol synthesis."	( Hepatic responses to inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase: a comparison of atorvastatin and simvastatin. Bergstrom, JD; Bostedor, RG; Chao, YS; Geissler, WM; Rew, DJ; Wright, SD, 1998)	0.51
" Concomitant use of potent inhibitors of CYP3A with simvastatin should be avoided or its dosage should be greatly reduced."	( Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Kantola, T; Kivistö, KT; Neuvonen, PJ, 1998)	1.99
" In accordance with manufacturers' recommendations, maximum dosage was atorvastatin 80 mg daily or simvastatin 40 mg daily (+cholestyramine 4 g daily in 84% of cases)."	( Comparison of atorvastatin alone versus simvastatin +/- cholestyramine in the management of severe primary hypercholesterolaemia (the six cities study). Simons, LA, 1998)	0.78
" As an alternative, the dosage of simvastatin should be reduced considerably, that is, by about 50% to 80%, at least when a simvastatin dosage higher than 20 mg/day is used."	( Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations. Kantola, T; Kivistö, KT; Neuvonen, PJ, 1998)	0.83
"Phase IIa clinical studies with cerivastatin--including 2 pilot US and European dose-ranging studies, and 1 US dose-scheduling study--were conducted to establish a dosage regimen and effective therapeutic doses of cerivastatin in the treatment of hypercholesterolemia."	( Clinical efficacy of cerivastatin: phase IIa dose-ranging and dose-scheduling studies. Hunninghake, DB, 1998)	0.3
" Data collected were demographics, number of simvastatin refills, dosage distribution, baseline and posttreatment lipid profiles, and proportion of patients with low-density lipoprotein (LDL) levels below target as recommended by the National Cholesterol and Education Program."	( The outcome of very low dosages of simvastatin in patients with hypercholesterolemia. Rindone, JP, 1999)	0.84
"Simvastatin was administered at a dosage of 5 mg/day for 24 weeks to 38 HD patients with high serum total cholesterol (TC) levels (200 mg/dl) or low high-density lipoprotein cholesterol (HDL-C) levels (35 mg/dl)."	( Effect of simvastatin on the lipid profile of hemodialysis patients. Kimura, K; Kishino, M; Maeda, A; Maeda, T; Miyano, M; Mune, M; Nishide, I; Nishide, T; Nishikawa, O; Ogawa, A; Otani, H; Takahashi, T; Tone, Y; Yukawa, S, 1999)	2.15
" These results indicate that NK-104 and simvastatin at 10 times the dosage of the former, similarly enhances hepatic LDL receptor; however, only NK-104 with prolonged action suppresses VLDL secretion to show higher cholesterol-lowering potency and triglyceride-reducing effect."	( Hypolipidemic effect of NK-104, a potent HMG-CoA reductase inhibitor, in guinea pigs. Aoki, T; Kitahara, M; Saito, Y; Sato, F; Suzuki, H; Tamaki, T, 1999)	0.57
"The therapeutic regimens investigated in the analysis were the American Heart Association (AHA) step II diet plus simvastatin (titrated to a maximum dosage of 20 mg/day) and AHA step II diet alone."	( Simvastatin after orthotopic heart transplantation. Costs and consequences. Krobot, KJ; Reichart, B; Wenke, K, 1999)	1.96
" During the development of simvastatin solid dosage form, formulation compositions were constantly varied to define a suitable matrix."	( Second-derivative UV spectrometric determination of simvastatin in its tablet dosage form. Asgharnejad, M; Wang, L, 2000)	0.85
" In other experiments carried out on endothelium-removed preparations and in medium containing the calcium antagonist, diltiazem (10(-5) and 10(-6) M), the contraction dose-response curves were significantly reduced and the same happened in the presence of the inhibitor of sarcoplasmic reticulum Ca-2+-ATPase, cyclopiazonic acid (CPA) (3 x 10(-6) M)."	( Endothelium modulates contractile response to simvastatin in rat aorta. Alvarez de Sotomayor, M; Herrera, MD; Marhuenda, E; Pérez-Guerrero, C, )	0.39
" The 10-mg dosage (a fourth or half that used in studies) is the most frequently dispensed."	( Growth in use of statins after trials is not targeted to most appropriate patients. Feely, J; Kelly, A; McGettigan, P, 2000)	0.31
" The dosage used in humans is also significantly lower and therefore it is expected to have a good safety margin."	( Development of thyroid follicular adenoma on simvastatin therapy. Goenka, S; McCord, EL, 2000)	0.57
" A venous blood sample for a baseline analysis and another after 4 months of simvastatin therapy at a dosage of 20 mg per day were taken."	( Effect of simvastatin therapy on paraoxonase activity and related lipoproteins in familial hypercholesterolemic patients. Covas, M; García-Faria, F; Marrugat, J; Sentí, M; Tomás, M; Torrents, A; Vila, J, 2000)	0.94
" These data demonstrate that multiple dosing of simvastatin, at the highest recommended clinical dose, does not significantly alter the in vivo hepatic or intestinal CYP3A4/5 activity as measured by the commonly used EBT and oral midazolam probes."	( Simvastatin does not affect CYP3A activity, quantified by the erythromycin breath test and oral midazolam pharmacokinetics, in healthy male subjects. Brucker, MJ; Gagliano, K; Gillen, L; Greenberg, HE; McLoughlin, D; Prueksaritanont, T; Rogers, JD; Vega, JM; Waldman, SA; Wong, PH, 2000)	2.01
" Mice were dosed daily for 6 weeks with simvastatin (100 mg/kg body wt)."	( Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering. Burton, CA; Chao, YS; Detmers, PA; Hassing, H; Hermanowski-Vosatka, A; Hernandez, M; Mundt, S; Patel, S; Peterson, L; Rosa, R; Sparrow, CP; Wang, PR; Wright, SD; Zhang, D, 2001)	2.02
" Simvastatin was well tolerated across the dosage range."	( Attaining United States and European guideline LDL-cholesterol levels with simvastatin in patients with coronary heart disease (the GOALLS study). Adams, PC; Brown, AS; Garmendia, F; Reiber, I, 2000)	1.45
" The medication dosage was doubled after 4 weeks if a subject's LDL-C was not less than 130 mg/dL."	( Simvastatin treatment on postprandial hypertriglyceridemia in type 2 diabetes mellitus patients with combined hyperlipidemia. Chen, YT; Jeng, CY; Lee, WJ; Lin, SY; Pei, D; Sheu, WH, 2001)	1.75
" The calculated average annual maintenance cost was based on the distribution of the final daily dosing regimens and the public drug prices for each regimen."	( Cost-minimization analysis of simvastatin versus atorvastatin for maintenance therapy in patients with coronary or peripheral vascular disease. Allen, SE; Attanasio, E; Russo, P, 2001)	0.6
" After a 6-week washout period, patients were randomized to 18 weeks of treatment at an initial dosage of simvastatin 10 mg once daily or fluvastatin 20 mg once daily."	( A comparison of the efficacy and tolerability of titrate-to-goal regimens of simvastatin and fluvastatin: a randomized, double-blind study in adult patients at moderate to high risk for cardiovascular disease. Buirma, RJ; den Hartog, FR; Kastelein, JJ; Kragten, HA; Penn, HJ; Trip, MD; van Dam, MJ, 2001)	0.75
"Two randomized, two-period crossover studies were conducted to evaluate the effects of repeat oral dosing of troglitazone (Study I) and pioglitazone (Study II) on the pharmacokinetics of plasma HMG-CoA reductase inhibitors following multiple oral doses of simvastatin and of simvastatin on the plasma pharmacokinetics of troglitazone (Study I) in healthy subjects."	( Interactions between simvastatin and troglitazone or pioglitazone in healthy subjects. Amin, RD; Dilzer, S; Gagliano, K; Kuznetsova, O; Lasseter, KC; Liu, L; Musser, B; Prueksaritanont, T; Roadcap, BA; Rogers, JD; Vega, JM; Zhao, J, 2001)	0.81
" The area under the curve (AUC) of simvastatin after concomitant dosing with itraconazole was predicted to increase ca."	( Inhibition of in vitro metabolism of simvastatin by itraconazole in humans and prediction of in vivo drug-drug interactions. Ikeda, T; Inoue, S; Ishigam, M; Ito, K; Iwabuchi, H; Komai, T; Kondo, T; Sugiyama, Y; Takasaki, W; Uchiyama, M, 2001)	0.86
" The second issue is whether early use of an aggressively dosed statin is superior to a current trial-based "accepted care" regimen of a lower-dose statin started 3 to 6 months after an acute event."	( The A-to-Z Trial: Methods and rationale for a single trial investigating combined use of low-molecular-weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy. Bilheimer, D; Blazing, MA; Braunwald, E; Califf, RM; De Lemos, JA; Dyke, CK, 2001)	0.5
" The dosage of simvastatin was based on the additional percent reduction in LDL cholesterol needed to achieve the goal specified by the National Cholesterol Education Program."	( Effect of pravastatin-to-simvastatin conversion on low-density-lipoprotein cholesterol. Dresselhaus, TR; Henry, RR; Ito, MK; Lin, JC; Marcus, DB; Morreale, AP; Shabetai, R, 2001)	0.97
" Dose-response curves of simvastatin for bone formation and resorption differed."	( Effect of statins on bone mineral density and bone histomorphometry in rodents. Conradie, MM; Gopal, R; Hough, S; Hulley, PA; Maritz, FJ, 2001)	0.61
" Six product brands encompassing 20 dosage strengths have been available during the past two years."	( Managed care trends in statin usage. Bazalo, GR, 2001)	0.31
" Trends in market share, mean daily dose, and dosage distribution of the six current statin brands were examined."	( Managed care trends in statin usage. Bazalo, GR, 2001)	0.31
" Nelfinavir increased the steady-state area under the plasma concentration-time curve during one dosing period (AUC(tau)) of atorvastatin 74% and the maximum concentration (C(max)) of atorvastatin 122% and increased the AUC(tau) of simvastatin 505% and the C(max) of simvastatin 517%."	( Pharmacokinetic interactions between nelfinavir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and simvastatin. Hsyu, PH; Kerr, BM; Lewis, RH; Lillibridge, JH; Schultz-Smith, MD, 2001)	0.7
"The greater reduction of plasma concentrations of 24S-hydroxycholesterol compared with cholesterol indicates that simvastatin in a dosage of 80 mg/d reduces cholesterol turnover in the brain."	( Reduction of plasma 24S-hydroxycholesterol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia: evidence that simvastatin affects cholesterol metabolism in the human brain. Beisiegel, U; Locatelli, S; Lütjohann, D; Otto, C; Schmidt, HH; von Bergmann, K, 2002)	0.75
"The investigation showed that half-tablet dosing was as effective as whole-tablet dosing."	( Effect of tablet splitting on serum cholesterol concentrations. Castle, SS; Duncan, MC; Streetman, DS, 2002)	0.31
" In subjects carrying a receptor-defective mutation, however, we observed that 51% of the variability in LDL-cholesterol response was explained by variations in the dosage of simvastatin expressed in mg/kg/day (P=0."	( Influence of LDL receptor gene mutation and apo E polymorphism on lipoprotein response to simvastatin treatment among adolescents with heterozygous familial hypercholesterolemia. Bergeron, J; Couture, P; Gagné, C; Lelièvre, M; Lupien, PJ; Szots, F; Vohl, MC, 2002)	0.73
"01) in high dosage Sim treatment group (n = 9) compared with LVH group."	( Effects of simvastatin on activities of endogenous antioxidant enzymes and angiotensin-converting enzyme in rat myocardium with pressure-overload cardiac hypertrophy. Luo, JD; Ou, HJ; Zhang, GP; Zhang, WW; Zhong, BH, 2002)	0.7
" In a third, non-randomized treatment period after a second wash-out interval, each woman received a combination of simvastatin and postmenopausal hormone therapy in the same dosage regimens as above."	( Concurrent use of simvastatin and estrogen--progestin therapy compared with each therapy alone for hypercholesterolemia in postmenopausal women. Darling, GM; Davis, SR; Johns, JA; McCloud, PI, 1999)	0.85
" To evaluate this effect further, dose-response curves with noradrenaline were measured in the presence and absence of 20 micromol/l simvastatin, lovastatin, mevastatin and pravastatin."	( Inhibition of smooth muscle cell calcium mobilization and aortic ring contraction by lactone vastatins. Altieri, PI; Crespo, MJ; Escobales, N; Furilla, RA, 1996)	0.5
"Neural networks have been used in diagnosing and treating many diseases, including the diagnosis of myocardial infarction and insulin dosing in diabetes mellitus."	( A preliminary evaluation of neural network analysis for pharmacodynamic modeling of the dosing of the hydroxymethylglutaryl coenzyme A-reductase inhibitors simvastatin and atorvastatin. Moon, A; Smith, T, 2002)	0.51
"The goal of this study was to develop a preliminary pharmacodynamic model for dosing of the hydroxymethylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors simvastatin and atorvastatin using neural network analysis."	( A preliminary evaluation of neural network analysis for pharmacodynamic modeling of the dosing of the hydroxymethylglutaryl coenzyme A-reductase inhibitors simvastatin and atorvastatin. Moon, A; Smith, T, 2002)	0.71
"A neural network model for the dosing of the HMG-CoA-reductase inhibitors simvastatin and atorvastatin demonstrated an ability to predict appropriate dosing, but inclusion of other factors (eg, age, body weight, sex) and a larger sample size may be necessary for development of a more accurate model."	( A preliminary evaluation of neural network analysis for pharmacodynamic modeling of the dosing of the hydroxymethylglutaryl coenzyme A-reductase inhibitors simvastatin and atorvastatin. Moon, A; Smith, T, 2002)	0.74
"A micellar electrokinetic chromatographic (MEKC) method was developed for the quantification of lovastatin and simvastatin, cholesterol lowering agents in pharmaceutical dosage forms."	( Determination of lovastatin and simvastatin in pharmaceutical dosage forms by MEKC. Raju, AN; Reddy, GO; Srinivasu, MK, 2002)	0.81
" However, atorvastatin had a different dose-response effect from simvastatin on both lipid parameters."	( Dose-response effects of atorvastatin and simvastatin on high-density lipoprotein cholesterol in hypercholesterolaemic patients: a review of five comparative studies. Mikhailidis, DP; Wierzbicki, AS, 2002)	0.82
" Seventeen per cent of the patients who were evaluated at 8 weeks increased the simvastatin dosage to 40 mg per day in the second month of treatment."	( Dose-expanded study in the reinforcement of efficacy of simvastatin. Vichayanrat, A, 2002)	0.79
"To avoid severe myopathy, cyclosporine levels should be monitored sooner than weekly intervals and statins should be discontinued or their dosage should be reduced, as long as azoles need to be prescribed in transplant recipients."	( Itraconazole-induced rhabdomyolysis and acute renal failure in a heart transplant recipient treated with simvastatin and cyclosporine. Alivizatos, PA; Chilidou, D; Manginas, A; Vlahakos, DV; Zamanika, C, 2002)	0.53
" The first group was the original product (Zocor), dosage 10 mg, Lot No IC4/36(N) from Merck Sharp & Dohme Company and the second group was a generic product, dosage 10 mg, Lot No T05/080 and T06/109 from Unison Company."	( A randomized crossover study to evaluate LDL-cholesterol lowering effect of a generic product of simvastatin (Unison Company) compared to simvastatin (Zocor) in hypercholesterolemic subjects. Assawawitoontip, S; Wiwanitkit, V, 2002)	0.53
"The simvastatin regimen for patients with a low-density lipoprotein cholesterol (LDL) level at their established National Cholesterol Education Program goal was converted from daily dosing to double the daily dose given every other day for 8 weeks."	( Daily dosing versus alternate-day dosing of simvastatin in patients with hypercholesterolemia. Copher, HR; Stewart, RD, 2002)	1.13
" The LDL-lowering effect of the daily dosing regimen was compared with that of the alternate-day dosing regimen."	( Daily dosing versus alternate-day dosing of simvastatin in patients with hypercholesterolemia. Copher, HR; Stewart, RD, 2002)	0.58
"Alternate-day dosing of simvastatin may be an effective alternative to daily dosing."	( Daily dosing versus alternate-day dosing of simvastatin in patients with hypercholesterolemia. Copher, HR; Stewart, RD, 2002)	0.88
" The four cases illustrate the importance of considering the potential for drug interactions and making appropriate dosage adjustments for renal insufficiency in patients receiving HMG CoA reductase therapy."	( HMG CoA reductase-inhibitor-related myopathy and the influence of drug interactions. Bagnall, F; Choy, T; Cordato, D; Dunn, R; Hitchens, N; Huynh, T; Johnstone, K; Yang, F, )	0.13
" A clinical pharmacist was responsible for laboratory monitoring, patient counseling, and the initiation and dosage adjustment of an appropriate 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) using a dosing algorithm and monitoring guidelines."	( A multidisciplinary program for achieving lipid goals in chronic hemodialysis patients. Abbott, KC; McMillan, RJ; Sheikh, AM; Viola, RA; Welch, PG; Yuan, CM, 2002)	0.31
" In addition, the low incidence of drug-related adverse events in this study may be also related to the low dosage of simvastatin."	( Sustained reduction of serum cholesterol in low-dose 6-year simvastatin treatment with minimum side effects in 51,321 Japanese hypercholesterolemic patients. Itakura, H; Kita, T; Mabuchi, H; Matsuzaki, M; Matsuzawa, Y; Nakaya, N; Oikawa, S; Saito, Y; Sasaki, J; Shimamoto, K, 2003)	0.77
" According to baseline levels of low density lipoprotein (LDL)-C, girls and boys were divided into two groups, one group (with LDL-C <220 mg/dl) starting with a simvastatin dosage of 5 mg/day, the other (with LDL-C >220 mg/dl) 10 mg/day with the possibility to increase dosages up to a daily maximum of 20 mg, if not reaching LDL-C concentrations of <170 mg/dl within the first period."	( The effect of low-dose simvastatin in children with familial hypercholesterolaemia: a 1-year observation. Bucek, RA; Dirisamer, A; Hachemian, N; Reiter, M; Widhalm, K; Wolf, F, 2003)	0.83
" Profiles of blood glucose concentration following repaglinide dosing were altered by less than 8% by both ketoconazole and rifampicin."	( Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide. Hansen, KT; Hatorp, V; Thomsen, MS, 2003)	0.32
" It also indicates that the clinical dosage of simvastatin are relatively smaller than that for satisfactory lipid control in patients with acute coronary syndromes."	( Lipid-lowering efficacy and safety of varying doses of Simvastatin in patients with early stage acute coronary syndromes: one-year follow-up study. Cui, L; Gao, M; Hu, D; Liu, X; Wei, Y; Xu, Z; Yang, X; Zou, Y, 2003)	0.82
"A 67-year-old man receiving a stable maintenance dosage of warfarin experienced an increased international normalized ratio (INR) without bleeding when his atorvastatin therapy was switched to fluvastatin."	( Oral anticoagulant drug interactions with statins: case report of fluvastatin and review of the literature. Andrus, MR, 2004)	0.32
" In treatment B, subjects received a 160-mg micronized fenofibrate capsule in the morning for 7 days, followed by a 160-mg micronized fenofibrate capsule dosed together with an 80-mg simvastatin tablet on days 8 to 14."	( Simvastatin does not have a clinically significant pharmacokinetic interaction with fenofibrate in humans. Bergman, AJ; Burke, J; Hartford, A; He, W; Lasseter, KC; Liu, L; Murphy, G; Paolini, JF; Prueksaritanont, T; Qiu, Y; Valesky, R; Vega, JM; Zhao, JJ, 2004)	1.96
" In both studies, simvastatin was generally well tolerated by all patients across the dosage range of 20 mg-80 mg."	( Efficacy and safety of simvastatin in Asian and non-Asian coronary heart disease patients: a comparison of the GOALLS and STATT studies. Bilheimer, D; Chung, N; Davies, MJ; Lee, K; Loeys, T; Morales, D; Sangwatanaroj, S; Shah, A; Yin, WH; Zhu, JR, 2004)	0.97
" 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg) and hence, the dosage may be adjusted to suit the individual patient's needs."	( Ezetimibe/Simvastatin: a review of its use in the management of hypercholesterolemia. Murdoch, D; Scott, LJ, 2004)	0.73
"0 mg/day, dosage was dependent on an initial level of total cholesterol)."	( The effect of simvastatin therapy on hemorheological profile in coronary heart desease (CHD) patients. Muravyov, AV; Petrochenko, A; Surovaya, L; Yakusevich, VV, 2004)	0.68
" Because of its long record of safety and demonstrated ability to reduce cardiovascular risk, simvastatin has recently become available without a prescription in the UK at the 10 mg dosage level."	( Simvastatin: a review. Pedersen, TR; Tobert, JA, 2004)	1.99
" Next, using the quantitative in vivo angiogenesis ELISA, we generated dose-response curves for each compound."	( Use of a monoclonal antibody specific for activated endothelial cells to quantitate angiogenesis in vivo in zebrafish after drug treatment. Eng, K; Lee, J; McGrath, P; Seng, WL, 2004)	0.32
" Instructions for dosage adjustment are seldom provided in the Japanese package inserts."	( A literature search on pharmacokinetic drug interactions of statins and analysis of how such interactions are reflected in package inserts in Japan. Hasegawa, R; Hirata-Koizumi, M; Miyake, S; Saito, M; Urano, T, 2005)	0.33
" This was similar for both statins and was treatment-duration dependent, only occurring after 10 days had elapsed even if the dose was increased, and still occurring after this time when dosing was terminated earlier as a result of morbidity."	( Statin-induced muscle necrosis in the rat: distribution, development, and fibre selectivity. Bigley, A; Marsden, AM; Randall, K; Scott, RC; Westwood, FR, 2005)	0.33
" Group I-treated with pravastatin, group II--with simvastatin--both drugs in a dosage of 40 mg/kg daily, 5 days/week for a total of 3 weeks."	( Effect of pravastatin, simvastatin and atorvastatin on the phagocytic activity of mouse peritoneal macrophages. Bergman, M; Bessler, H; Djaldetti, M; Salman, H, 2006)	0.9
" On the day of the experiment the kidney was prepared for videomicroscopy and dose-response curves were done with acetylcholine and sodium nitroprusside (10(-10) M to 10(-5) M) in simvastatin-fed rats ??(n=8) and control rats (n=13)."	( Enhanced acetylcholine-induced dilation in afferent arterioles in simvastatin-fed rats. Caprio, TW; Drummond, E; Entenman, K; Inman, SR; Mueller, M, 2006)	0.76
" Simvastatin was administered, in both groups, at a dosage of 20 mg/day, while l-carnitine was administered at a dosage of 2g/day once daily."	( Efficacy and tolerability of combined treatment with L-carnitine and simvastatin in lowering lipoprotein(a) serum levels in patients with type 2 diabetes mellitus. Capurso, A; Capurso, C; Capurso, SA; Colacicco, AM; D'Introno, A; Fontana, C; Gadaleta, AM; Koverech, A; Panza, F; Solfrizzi, V; Torres, F, 2006)	1.48
" No meaningful changes in the body weight were detected in all dosing groups compared to that of vehicle control group."	( Hypolipemic effect of water extracts of Picrorrhiza rhizoma in PX-407 induced hyperlipemic ICR mouse model with hepatoprotective effects: a prevention study. Ahn, HC; Ku, SK; Lee, HS, 2006)	0.33
"We searched Medline, the international medical database, to conduct a systematic review of the literature on the efficacy and tolerability of statins in CKD and renal transplant patients and on specific recommendations for dosage adjustments in this population."	( [Statins in patients with kidney failure: efficacy, tolerance, and prescription guidelines in patients with chronic kidney disease and renal transplant]. Deray, G; Isnard-Bagnis, C; Karie, S; Launay-Vacher, V, 2006)	0.33
" Although most statins are not excreted by the kidneys, the dosage of some must be adapted in CKD patients because of pharmacokinetic modifications induced by renal impairment."	( [Statins in patients with kidney failure: efficacy, tolerance, and prescription guidelines in patients with chronic kidney disease and renal transplant]. Deray, G; Isnard-Bagnis, C; Karie, S; Launay-Vacher, V, 2006)	0.33
"The lowest and highest dosage strengths of EZE/SIMVA tablet were bioequivalent to the individual drug components administered together."	( Bioequivalence of an ezetimibe/simvastatin combination tablet and coadministration of ezetimibe and simvastatin as separate tablets in healthy subjects. Bergman, A; Gambale, J; Gottesdiener, K; Groff, M; Hreniuk, D; Johnson-Levonas, AO; Kosoglou, T; Lasseter, KC; Laurent, A; Liu, L; Matthews, N; Migoya, EM; Murphy, G; Musson, DG; Paolini, JF; Riffel, K; Roadcap, B; Statkevich, P; Valesky, R; Yi, B; Zhao, JJ, 2006)	0.62
"Physicians' and pharmacists' ability to correctly identify three commonly used oral dosage forms was assessed."	( Ability of practitioners to identify solid oral dosage tablets. Bates, DW; Bult, J; Kim, S; Schiff, GD; Seger, AC, 2006)	0.33
" Participants were also asked about their experiences and views on current resources and alternatives for identifying oral dosage forms."	( Ability of practitioners to identify solid oral dosage tablets. Bates, DW; Bult, J; Kim, S; Schiff, GD; Seger, AC, 2006)	0.33
" Overall, 77% expressed dissatisfaction with the current system and 91% favored a universal imprint coding system for oral dosage forms."	( Ability of practitioners to identify solid oral dosage tablets. Bates, DW; Bult, J; Kim, S; Schiff, GD; Seger, AC, 2006)	0.33
" Differential pulse and square wave voltammetric methods for the quantitative determination of SMV in pharmaceutical dosage forms and spiked serum samples were developed based on the linear relationship between the peak current and the concentration."	( Determination of the antihyperlipidemic simvastatin by various voltammetric techniques in tablets and serum samples. Coruh, O; Ozkan, SA, 2006)	0.6
" After 14 days of dosing to achieve steady state, no significant differences were found in either the extent (AUC(tau)) or rate (Cmax) of exposure to simvastatin or its major beta-hydroxy metabolite after coadministration of P-OM3 with simvastatin compared with administration of simvastatin alone."	( Study of the pharmacokinetic interaction between simvastatin and prescription omega-3-acid ethyl esters. Di Spirito, M; Doyle, R; Kling, D; McKenney, JM; Pantaleon, C; Shalwitz, RA; Swearingen, D, 2006)	0.79
"Although previous studies have demonstrated that various "statins" decrease levels of high-sensitivity C-reactive protein (hs-CRP), the dose-response relation for lowering hs-CRP by the clinically important drug simvastatin compared with lipid lowering is unclear."	( Comparison of effects of high (80 mg) versus low (20 mg) dose of simvastatin on C-reactive protein and lipoproteins in patients with angiographic evidence of coronary arterial narrowing. Anderson, JL; Horne, BD; Lappe, DL; Maycock, CA; Meredith, KG; Muhlestein, JB; Pearson, RR, 2007)	0.76
" The steady-state pharmacokinetics of valsartan, simvastatin beta-hydroxy acid (active metabolite of simvastatin) and simvastatin (pro-drug) were determined on day 7 of each dosing period."	( Evaluation of a pharmacokinetic interaction between valsartan and simvastatin in healthy subjects. Humbert, H; Pommier, F; Prasad, P; Reynolds, CV; Sunkara, G; Yeh, C, 2007)	0.83
"Based on the wide therapeutic dosage ranges of valsartan and simvastatin, and the highly variable pharmacokinetics of three analytes, the observed differences in the exposure and C(max) of valsartan, simvastatin beta-hydroxy acid and simvastatin in the combination treatment are unlikely to be of clinical relevance."	( Evaluation of a pharmacokinetic interaction between valsartan and simvastatin in healthy subjects. Humbert, H; Pommier, F; Prasad, P; Reynolds, CV; Sunkara, G; Yeh, C, 2007)	0.82
" Statins were replaced with an equal dosage of fluvastatin."	( Fluvastatin as co-medication in heart transplant recipients with elevated creatine-kinase. Delgado, O; Kaczmarek, I; Meiser, B; Reichart, B; Sadoni, S; Schmöckel, M, 2007)	0.34
" The decline in motor functions associated with scrapie infection was delayed in mice receiving (1 mg/kg) simvastatin, a dosage used to treat hypercholesterolemia in humans."	( Simvastatin treatment prolongs the survival of scrapie-infected mice. Bate, C; Kempster, S; Williams, A, 2007)	2
" Canadian data on statin dosing were combined with efficacy data from a published meta-analysis to determine the proportion of patients who would be expected to achieve LDL-C targets after treatment with atorvastatin or generic simvastatin."	( A model for assessing the cost-effectiveness of atorvastatin and simvastatin in achieving Canadian low-density lipoprotein cholesterol targets. Lachaine, J; Merikle, E; Montpetit, M; Rinfret, S; Tarride, JE, 2007)	0.76
" This has lead to a series of international and national recommendations for a further reduction in target values for LDL-cholesterol, which is often difficult to achieve with the usual dosage of statins."	( [Dual inhibition of cholesterol using the drug combination ezetimibe/simvastatin?]. Vaverková, H, 2007)	0.57
" The results suggest that the effect of hydrophobic statins on the engulfing capacity of human peripheral blood phagocytes and apoptosis is dependent on their dosage and physiochemical properties."	( Hydrophobic but not hydrophilic statins enhance phagocytosis and decrease apoptosis of human peripheral blood cells in vitro. Bergman, M; Bessler, H; Djaldetti, M; Salman, H, 2008)	0.35
" The proposed method can be useful in the quality control of bulk manufacturing and pharmaceutical dosage forms."	( Stability-indicating reversed-phase liquid chromatographic method for simultaneous determination of simvastatin and ezetimibe from their combination drug products. Chaudhari, BG; Patel, NM; Shah, PB, )	0.35
" By blocking both synthesis and absorption of cholesterol, the fixed combination exerts a cholesterol-lowering effect as important as, or even greater than, that observed with the highest dosage of simvastatin and other statins, with a good tolerance profile."	( [Drug of the month. Ezetimibe/simvastatin tablet (Inegy)]. Radermecker, RP; Scheen, AJ, 2007)	0.82
" Our objective was to explore how differences in prevalences of use, dosing characteristics, choice of statin and continuity of therapy in individual patients adds new information to previous results."	( Aspects of statin prescribing in Norwegian counties with high, average and low statin consumption - an individual-level prescription database study. Eggen, AE; Engeland, A; Furu, K; Hartz, I; Njølstad, I; Sakshaug, S; Skurtveit, S, 2007)	0.34
"A reversed-phase liquid chromatographic (LC) method was developed and validated for the simultaneous determination of ezetimibe and simvastatin in pharmaceutical dosage forms."	( Simultaneous liquid chromatographic determination of ezetimibe and simvastatin in pharmaceutical products. Barth, T; Dalmora, SL; Oliveira, PR; Todeschini, V, )	0.57
"To target drug release and to assess regional gastrointestinal absorption of the CYP 3A substrate simvastatin from the distal parts of the intestine, delayed release film coated tableted oral dosage forms were developed."	( Pharmacokinetics of the CYP 3A substrate simvastatin following administration of delayed versus immediate release oral dosage forms. Amidon, GL; Hilfinger, JM; Kijek, P; Kim, JS; Langguth, P; Staubach, P; Tubic-Grozdanis, M, 2008)	0.83
" The overall metabolite levels from the immediate release capsules tended to be higher throughout the period studied than the metabolite levels following administration of Zocor and simvastatin delayed release dosage form."	( Pharmacokinetics of the CYP 3A substrate simvastatin following administration of delayed versus immediate release oral dosage forms. Amidon, GL; Hilfinger, JM; Kijek, P; Kim, JS; Langguth, P; Staubach, P; Tubic-Grozdanis, M, 2008)	0.8
" Unlike the majority of pharmacists, most GPs thought that current dosing guidelines were inappropriate, but there was consensus that long-term nonadherence would probably curtail any treatment benefit."	( Lifestyle or life-saving medicines? A primary healthcare professional and consumer opinion survey on over-the-counter statins. Greenfield, SM; Kountouri, M; Marshall, T; Vamvakopoulos, JE, 2008)	0.35
" Patients were randomized to an 8- or 12-week niacin titration scheme to a maximum NER/S dosage of 2,000/40 mg/day."	( Long-term safety and efficacy of a combination of niacin extended release and simvastatin in patients with dyslipidemia: the OCEANS study. Bajorunas, DR; Davidson, MH; Karas, RH; Kashyap, ML; Keller, LH; Knopp, RH, 2008)	0.57
" Statin dosage should be judiciously monitored in patients who are diabetic or are at risk of developing other forms of proliferative retinopathy."	( The pleiotropic effects of simvastatin on retinal microvascular endothelium has important implications for ischaemic retinopathies. Devine, AB; Gardiner, TA; Medina, RJ; O'Neill, CL; Stitt, AW, 2008)	0.64
"A dosing algorithm including genetic (VKORC1 and CYP2C9 genotypes) and nongenetic factors (age, weight, therapeutic indication, and cotreatment with amiodarone or simvastatin) explained 51% of the variance in stable weekly warfarin doses in 390 patients attending an anticoagulant clinic in a Brazilian public hospital."	( Pharmacogenetics of warfarin: development of a dosing algorithm for brazilian patients. Dias-Neto, E; Ojopi, EB; Perini, JA; Rangel, F; Santana, IS; Silva-Assunção, E; Struchiner, CJ; Suarez-Kurtz, G, 2008)	0.54
"Eligible patients had a 6-month period of no statin use prior to the initial statin prescription, an initial statin dosage of either 20 or 40 mg of simvastatin or 10 or 20 mg of atorvastatin (the most commonly used doses of both drugs), a 0 to 3-month 'qualifying period' after the first prescription to allow for varying minimum lengths of statin use, and no statin switches."	( Differences in cardiovascular event rates between atorvastatin and simvastatin among new users: managed-care experience. Vogel, RA; Willke, RJ; Zhou, S, 2008)	0.78
"The authors conducted a prospective, controlled, open-label trial examining the effectiveness and safety of high-dose fluvastatin or a standard dosage of simvastatin plus ezetimibe, both with an intensive guideline-oriented cardiac rehabilitation program, in achieving the new ATP III LDL-C targets in patients with proven coronary artery disease."	( Simvastatin and ezetimibe in addition to nonpharmacological risk factor modification for achieving new low-density lipoprotein cholesterol targets. Abdel-Wahab, M; Geist, V; Herrmann, L; Khattab, AA; Liska, B; Richardt, G; Tölg, R; Westphal, R, 2008)	1.99
" The direct application of study observations to clinical practice is limited by patient selection criteria and dosage regime, which randomly applied relatively high doses rather than titration which often occurs in clinical practice."	( Long-term (48-week) safety of ezetimibe 10 mg/day coadministered with simvastatin compared to simvastatin alone in patients with primary hypercholesterolemia. Bays, H; Capece, R; Liu, J; Sapre, A; Taggart, W; Tershakovec, A, 2008)	0.58
" The initial dose administered to patients in the extension was ezetimibe 10 mg coadministered with simvastatin 10 mg with the option to up-titrate statin dosage if LDL-C goals were not met."	( Long-term safety and tolerability of ezetimibe coadministered with simvastatin in hypercholesterolemic patients: a randomized, 12-month double-blind extension study. Hanson, ME; Strony, J; Veltri, EP; Yang, B, 2008)	0.8
" dosing with SV alone."	( Effect of oral ketoconazole on oral and intravenous pharmacokinetics of simvastatin and its acid in cynomolgus monkeys. Fukuzaki, K; Kume, T; Nii, K; Ogasawara, A; Ueda, A; Utoh, M; Yoshikawa, T, 2009)	0.59
" Animals were dosed daily with 80 mg kg(-1) day(-1) simvastatin for 4 (n = 6) and 12 days (n = 5), 88 mg kg(-1) day(-1) simvastatin for 12 days (n = 4), or vehicle (0."	( Blunted Akt/FOXO signalling and activation of genes controlling atrophy and fuel use in statin myopathy. Constantin-Teodosiu, D; Greenhaff, PL; Mallinson, JE; Sidaway, J; Westwood, FR, 2009)	0.6
"The drugs were given to the diabetic rats for 2 weeks; oxidative stress was measured by dosage of total plasma antioxidant capacity (TRAP) and malondialdehyde (MDA)."	( [Effects of ramipril and simvastatin on the oxidative stress of diabetic rats]. Barbosa, DS; Delfino, VD; Elias, JA; Fabris, BA; Matsuo, T, 2008)	0.65
"022) compared with no treatment, and there was an apparent dose-response effect with the lowest levels of total testosterone seen in men treated with >or=20 mg atorvastatin (9."	( Statin therapy is associated with lower total but not bioavailable or free testosterone in men with type 2 diabetes. Channer, KS; Jones, TH; Kapoor, D; Stanworth, RD, 2009)	0.35
" In a case of predisposition to RML statin therapy and dosage can only be performed under continuous supervision."	( [Maximal initial dose of simvastatin causing acute renal failure through rhabdomyolysis: risk factors, pathomechanism and therapy related to a case]. Al-Hadad, A; Deme, D; Rakonczai, E; Sándor, K; Szántó, E; Varga, T, 2009)	0.66
" The aims of this pilot study were to find the dosage and short-term efficacy of simvastatin and potential adverse events in children with chronic kidney diseases."	( Efficacy of simvastatin in children with hyperlipidemia secondary to kidney disorders. Arredondo-García, JL; Bojorquez-Ochoa, A; García-de-la-Puente, S; Gutiérrez-Castrellón, P; Maya, ER; Pérez-Martínez, Mdel P, 2009)	0.96
" The effects of simvastatins based on different methods of administration, dosage and carriers were also described."	( The use of simvastatin in bone regeneration. Park, JB, 2009)	1.09
" The impact of T2 on the dose-response to IGF-I (0, 3, 10 and 30 ng/mL) was also evaluated; T2 blunted the stimulatory effect of 3-30 ng/mL of IGF-I on steroid production and cell proliferation."	( Effects of a trichothecene, T-2 toxin, on proliferation and steroid production by porcine granulosa cells. Caloni, F; Cremonesi, F; Ranzenigo, G; Spicer, LJ, 2009)	0.35
" Test substances (either simvastatin low- or high dosed or BMP-2) were incorporated into a biodegradable layer of poly(d,l-lactide)."	( Simvastatin locally applied from a biodegradable coating of osteosynthetic implants improves fracture healing comparable to BMP-2 application. Haas, NP; Luttosch, F; Morawski, M; Pauly, S; Schmidmaier, G; Wildemann, B, 2009)	2.1
" The observation that simvastatin inhibited the apoptosis of HG-treated LECs in its therapeutic concentration suggests that daily dosage of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor used by diabetic patients may increase PCO formation."	( Apoptosis of lens epithelial cells induced by high concentration of glucose is associated with a decrease in caveolin-1 levels. Jin, C; Yao, K; Zhang, Z, 2009)	0.67
" The practical opportunity to reduce the risk of acute vascular events, improvement of vascular endothelium function and relative safety of application of the preparation in the specified dosage at persons of senile age is shown."	( [Pleiotropic effects of small dozes simvastatin in patients of senile age with chronic heart failure]. Al'tman, DA; Davydova, EV; Ermak, EM; Pirogov, AL, 2009)	0.63
"5 mg/dl) mainly regardless of previous statin therapy (rosuvastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, and lovastatin) and dosing (pooled median values)."	( [Achievement of blood lipid target levels with Ezetimibe/Simvastatin in patients with atherosclerosis and/or diabetes mellitus--an Austrian observational study]. Slany, J, 2009)	0.82
" The Entero-Test was used to collect bile from six fasted dogs that had been dosed either orally with simvastatin (SV) or intravenously with simvastatin hydroxy acid (SVA), compounds that have been previously reported to undergo extensive metabolism and biliary secretion in the dog."	( Use of the entero-test, a novel approach for the noninvasive capture of biliary metabolites in dogs. Beaumont, C; Guiney, WJ; Thomas, SR, 2010)	0.58
" Patients switched to an equivalent simvastatin dose had lower LDL-C levels and were more likely to achieve LDL-C targets than patients switched to a non-equivalent dose, suggesting physicians must consider dosage equivalence when switching statins, and should measure LDL-C and titrate statins as necessary to achieve LDL-C control."	( LDL-C goal attainment in patients who remain on atorvastatin or switch to equivalent or non-equivalent doses of simvastatin: a retrospective matched cohort study in clinical practice. Burke, JP; Rublee, DA, 2010)	0.85
" Multivariate analysis showed that statin dosage was independently associated with MD (OR:1."	( Mitochondrial dysfunction induced by statin contributes to endothelial dysfunction in patients with coronary artery disease. Chan, HT; Dai, YL; Fong, B; Lau, CP; Lee, SW; Li, SW; Luk, TH; Siu, CW; Tam, S; Tse, HF; Yiu, KH, 2010)	0.36
" Eight male subjects (BMI 25 +/- 3 kg/m(2)) with mild hypercholesterolemia (LDL cholesterol 135 +/- 30 mg/dL) and normal triglycerides (111 +/- 44 mg/dL) were examined under no treatment (A), under chronic treatment with simvastatin 40 mg/day (B) and after an acute-on-chronic dosage of 80 mg simvastatin under chronic simvastatin treatment (C)."	( Influence of simvastatin on apoB-100 secretion in non-obese subjects with mild hypercholesterolemia. Barrett, PH; Berthold, HK; Birnbaum, J; Brämswig, S; Gouni-Berthold, I; Mertens, J; Sudhop, T; von Bergmann, K, 2010)	0.91
" Furthermore, the following trends of interest were calculated for each calendar year: the percentage of statin users prescribed simvastatin or atorvastatin, the median dose of simvastatin and atorvastatin prescribed, and the percentage of simvastatin users prescribed a dosage of 40 mg/day (which is recommended by the Dutch multidisciplinary guideline)."	( Statin prescribing in the elderly in the Netherlands: a pharmacy database time trend study. Geleedst-De Vooght, M; Jansen, P; Maitland-van der Zee, AH; Mantel-Teeuwisse, A; Schalekamp, T, 2010)	0.57
"To explore if non-concurrent amlodipine dosing results in less drug interaction, the pharmacokinetic profiles, safety and efficacy endpoints were assessed following repeated doses of simvastatin, co-administered concurrently or non-concurrently with amlodipine in patients with coexisting hypertension and hyperlipidemia."	( Non-concurrent dosing attenuates the pharmacokinetic interaction between amlodipine and simvastatin. Choi, JW; Kim, SH; Lee, H; Lee, SJ; Lim, HE; Park, CG, 2010)	0.77
"The Cmax and AUClast and of simvastatin acid in the non-concurrent amlodipine dosing group were 63."	( Non-concurrent dosing attenuates the pharmacokinetic interaction between amlodipine and simvastatin. Choi, JW; Kim, SH; Lee, H; Lee, SJ; Lim, HE; Park, CG, 2010)	0.88
"Non-concurrent dosing may be a useful and safe therapeutic option for patients who require two or more drugs administered concomitantly, but who are likely to develop unwanted drug interactions."	( Non-concurrent dosing attenuates the pharmacokinetic interaction between amlodipine and simvastatin. Choi, JW; Kim, SH; Lee, H; Lee, SJ; Lim, HE; Park, CG, 2010)	0.58
" These results suggest that more research needs to be done to fully ascertain the therapeutic potential and optimal dosing paradigm of a post-ischemic treatment with a statin."	( Comparison of the post-embolization effects of tissue-plasminogen activator and simvastatin on neurological outcome in a clinically relevant rat model of acute ischemic stroke. Guluma, KZ; Lapchak, PA, 2010)	0.59
"Two spectrophotometric methods are presented for the simultaneous determination of ezetimibe/simvastatin and ezetimibe/atorvastatin binary mixtures in combined pharmaceutical dosage forms without prior separation."	( Enhanced spectrophotometric determination of two antihyperlipidemic mixtures containing ezetimibe in pharmaceutical preparations. Barary, MA; El-Kimary, EI; Hassan, EM; Maher, HM; Youssef, RM, 2011)	0.59
" The dosage administrated were 250 mg niacin-ER plus 10 mg SV in the first two weeks, 500 mg/20 mg in the next two weeks, and 750 mg/20 mg in the final four weeks."	( Effects of low-dose of niacin associated to simvastatin in the treatment of mixed dyslipidemia Salgad. Casulari, LA; Dos Santos, AM; Salgado, BJ; Salgado, JV, 2010)	0.62
"A 63-year-old man with a history of chronic renal impairment on a stable dosage of simvastatin developed rhabdomyolysis after the addition of ranolazine to his medication regimen."	( Rhabdomyolysis in a patient receiving ranolazine and simvastatin. Ezekiel, TO; Hylton, AC, 2010)	0.84
" The decrease can be prevented by the suggested dosage scheme."	( Use of ultra high performance liquid chromatography-tandem mass spectrometry to demonstrate decreased serum statin levels after extracorporeal LDL-cholesterol elimination. Bláha, M; Bláha, V; Lánská, M; Malý, J; Nováková, L; Solich, P; Solichová, D; Vlcková, H, 2011)	0.37
" On post burn day 7 cecal ligation and puncture with a 21-gauge needle (CLP) was performed under ketamine/xylazine anesthesia, the two different dosing schedules were continued and survival was monitored."	( Simvastatin treatment improves survival in a murine model of burn sepsis: Role of interleukin 6. Beffa, DC; Carter, EA; Fagan, SP; Fischman, AJ; Hamrahi, VF; Kaneki, M; Paul, KW; Tompkins, RG; Yu, YM, 2011)	1.81
"Simple, accurate, sensitive, and precise UV spectrophotometric, chemometric, and HPLC methods were developed for simultaneous determination of a two-component drug mixture of ezetimibe (EZ) and simvastatin (SM) in laboratory-prepared mixtures and a combined tablet dosage form."	( Quantitative analysis of the cholesterol-lowering drugs ezetimibe and simvastatin in pure powder, binary mixtures, and a combined dosage form by spectrophotometry, chemometry, and high-performance column liquid chromatography. Aboul Alamein, AM; Hegazy, MA; Lotfy, HM, )	0.55
"Numerous metabolites of simvastatin were detected, and the major metabolites were consistent with those reported from studies where bile was collected using invasive techniques from patients dosed with [(14) C]-simvastatin."	( Use of Entero-Test, a simple approach for non-invasive clinical evaluation of the biliary disposition of drugs. Beaumont, C; Guiney, WJ; Koch, A; McHugh, SM; Richards, D; Robertson, DC; Thomas, SR, 2011)	0.68
" The objectives of the present study were to develop a population pharmacokinetic-pharmacodynamic (PK-PD) model for simvastatin and to evaluate its usefulness in predicting the dose-response relationship of simvastatin in patients with hyperlipidaemia."	( A population pharmacokinetic-pharmacodynamic model for simvastatin that predicts low-density lipoprotein-cholesterol reduction in patients with primary hyperlipidaemia. Ahn, BJ; Chae, HS; Choi, J; Doh, K; Han, S; Jun, YK; Kim, J; Lee, YW; Yim, DS, 2011)	0.83
" To optimize the dose regimens of these inducers for use in DDI studies, their effect at various doses and dosing durations on the area under the curve (AUC) of multiple probe substrates was simulated using a population-based simulator."	( Simulation of clinical drug-drug interactions from hepatocyte CYP3A4 induction data and its potential utility in trial designs. Hayashi, M; Shou, M; Skiles, GL; Xu, Y; Zhou, Y, 2011)	0.37
" Simvastatin was discontinued and dosage of cholinesterase inhibitor was temporarily increased."	( Statin-associated myasthenic weakness. Pasutharnchat, N; Phanthumchinda, K, 2011)	1.28
" The incidence ofstatin-associated myasthenic weakness should be clearly investigated Challenge with other brands of statin or with reduced dosage is not beneficial in these patients."	( Statin-associated myasthenic weakness. Pasutharnchat, N; Phanthumchinda, K, 2011)	0.37
"Data were pooled from eight NER studies (administered as NER with a maximum dosage of 1000, 1500, and 2000 mg/day, either as monotherapy or in combination with simvastatin 20 or 40 mg/day [NER/S], or lovastatin 20 or 40 mg/day [NER/L]) to evaluate rates of study discontinuation due to flushing or any treatment-related adverse events."	( Niacin extended-release therapy in phase III clinical trials is associated with relatively low rates of drug discontinuation due to flushing and treatment-related adverse events: a pooled analysis. Brinton, EA; Jiang, P; Kashyap, ML; Padley, RJ; Thakkar, RB; Vo, AN, 2011)	0.57
" We proposed a systematic classification scheme using FDA-approved drug labeling to assess the DILI potential of drugs, which yielded a benchmark dataset with 287 drugs representing a wide range of therapeutic categories and daily dosage amounts."	( FDA-approved drug labeling for the study of drug-induced liver injury. Chen, M; Fang, H; Liu, Z; Shi, Q; Tong, W; Vijay, V, 2011)	0.37
"9% saline (control group) or lipid emulsion (high fat group) at the daily dosage of 15 ml/kg body weight, respectively."	( Effects of simvastatin on apolipoprotein M in vivo and in vitro. Berggren-Söderlund, M; Luo, G; Mao, S; Nilsson-Ehle, P; Wei, J; Xu, N; Zhang, X, 2011)	0.76
" Evening dosing resulted in significant dose-dependent improvement in latency to persistent sleep, total sleep time and wake after sleep onset as measured by polysomnography."	( Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist. Alexander, R; Bettica, P; Gomeni, R; Nucci, G; Pyke, C; Ratti, E; Squassante, L; Zamuner, S, 2012)	0.38
"The aim of this study was to explore the influence of simvastatin dosing time, variable compliance and circadian cholesterol production on the reduction of low-density lipoprotein (LDL)."	( The influence of dosing time, variable compliance and circadian low-density lipoprotein production on the effect of simvastatin: simulations from a pharmacokinetic-pharmacodynamic model. Al-Sallami, HS; Duffull, SB; Pavan Kumar, VV; Wright, DF, 2011)	0.83
" No subject discontinued dosing due to adverse events."	( Open-label phase 1b pilot study to assess the antiviral efficacy of simvastatin combined with sertraline in chronic hepatitis C patients. Altmeyer, R; Cheng, CW; Chopra, N; Lawitz, E; Lim, SG; McHutchison, JG; Patel, K; Randle, JC; Tillmann, HL, 2011)	0.6
" However, at these dosage levels HDL-cholesterol showed respective percent increase of 42, 48 and 53."	( Lipid lowering effect of Cinnamomum zeylanicum in hyperlipidaemic albino rabbits. Ahmad, M; Aslam, B; Faisal, I; Javed, I; Khan, MZ; Muhammad, F; Rahman, Z; Shahzadi, A, 2012)	0.38
" To facilitate translation to clinical practice, we now characterize the optimal statin and dosing paradigm in murine models of ICH and TBI."	( Statins improve outcome in murine models of intracranial hemorrhage and traumatic brain injury: a translational approach. Dawson, HN; Indraswari, F; James, ML; Kernagis, D; Laskowitz, DT; Lei, B; Wang, H; Warner, DS, 2012)	0.38
"The dose-response of the pleiotropic effects of statins on airway inflammation has not yet been established and may differ from that of their cholesterol-lowering effects."	( Simvastatin delivery via inhalation attenuates airway inflammation in a murine model of asthma. Cao, R; Dong, XW; Jiang, JX; Li, FF; Shen, HJ; Shen, LL; Sun, Y; Xie, QM; Xu, L; Yao, HY, 2012)	1.82
" In rhesus monkeys, subcutaneous (SC) dosing of 1B20 dose-dependently induces robust LDL-C lowering (maximal ~70%), which is correlated with increases in target engagement and total antibody-bound PCSK9 levels."	( An anti-PCSK9 antibody reduces LDL-cholesterol on top of a statin and suppresses hepatocyte SREBP-regulated genes. An, Z; Ansbro, F; Blom, D; Chilewski, S; Chin, J; Condra, JH; Cumiskey, AM; Ernst, R; Geoghagen, N; Hammond, H; Hampton, R; Hansen, BC; Haytko, P; Huang, L; Hubbard, B; Jensen, K; Johns, DG; Lewis, D; McCabe, T; Mendoza, V; Mitnaul, LJ; Ni, YG; Pandit, S; Pellacani, A; Peterson, LB; Plump, AS; Rosa, R; Shen, X; Sitlani, A; Sparrow, CP; Strack, AM; Strohl, W; Wang, F; Wang, W; Wietecha, K; Wisniewski, D; Wood, D; Zhang, L; Zhao, JZ; Zhu, L, 2012)	0.38
" The strong inductive effect of TNF-α on VCAM-1 was counteracted by simvastatin and shear stress in an additive dose-response dependent way."	( Effect of shear stress, statins and TNF-α on hemostatic genes in human endothelial cells. Bergh, N; Jern, S; Larsson, P; Ulfhammer, E, 2012)	0.61
" Patients were stratified according to statin and dosage to identify against-label combination use (e."	( Persistent use of against-label statin-fibrate combinations from 2003-2009 despite United States Food and Drug Administration dose restrictions. Alford, JC; Allen, RR; Nair, KV; Saseen, JJ, 2012)	0.38
"2%, usually atorvastatin), or increasing atorvastatin dosage (59."	( Effectiveness of lipid-lowering therapy with statins for secondary prevention of atherosclerosis--guidelines vs. reality. Bożentowicz-Wikarek, M; Chudek, J; Kocełak, P; Olszanecka-Glinianowicz, M; Smertka, M, 2012)	0.38
"In the absence of clinical studies, the ability to project the direction and the magnitude of changes in bioavailability of drug therapy, using evidence-based mechanistic pharmacokinetic in silico models would be of significant value in guiding prescribers to make the necessary adjustments to dosage regimens for an increasing population of patients who are undergoing bariatric surgery."	( A mechanistic pharmacokinetic model to assess modified oral drug bioavailability post bariatric surgery in morbidly obese patients: interplay between CYP3A gut wall metabolism, permeability and dissolution. Ammori, BJ; Ashcroft, DM; Darwich, AS; Jamei, M; Pade, D; Rostami-Hodjegan, A, 2012)	0.38
" This study shows a simple and fast method validation by reversed-phase high-performance liquid chromatography in the linear range 28 to 52 µg/mL to quantify lovastatin, pravastatin sodium or simvastatin in bulk drug or dosage forms."	( Development and validation of a simple and fast HPLC method for determination of lovastatin, pravastatin and simvastatin. de Oliveira, RB; Oliveira, MA; Silva, TD; Vianna-Soares, CD, 2012)	0.78
"Muscular symptoms associated with average dosage statin therapy are more frequent than in clinical trials and have a greater impact on patients' life than usually thought."	( Discontinuation of statin therapy due to muscular side effects: a survey in real life. Bruckert, E; Dallongeville, J; Rosenbaum, D; Sabouret, P, 2013)	0.39
" There may be a direct relationship between the dosage of wenxiao II decoction and its therapeutic efficacy."	( Effects of Wenxiao II decoction on the expression of MCP-1 and VCAM-1 in atherosclerotic rabbits. Huo, QP; Liu, HY; Wang, YX, 2012)	0.38
" Thus, most exigent phase of drug development practice particularly for oral dosage forms is the enhancement of drug solubility and thereby its oral bioavailability."	( Solubility enhancement of simvastatin: a review. Murtaza, G, )	0.43
" The main objective is to improve solubility of simvastatin beta-CD complex (1:2) by co-precipitation method and then to deliver the same in sustained release dosage form."	( Preparation and statistical optimization of alginate based stomach specific floating microcapsules of simvastatin. Barik, BB; Premchandani, TA, )	0.6
" The justifications and benefits of combination therapy are far-reaching, including but not limited to addressing unmet medical needs such as cancer, malaria, and HIV/AIDS, improved clinical efficacy and safety with reduced dosage of a single medication, understanding the underlying science of the disease, alleviating pharmaco-economic impacts, and better drug life-cycle management."	( A case study of single-pill combination therapy: the ezetimibe/simvastatin combination for treatment of hyperlipidemia. Chen, DY; Huang, X, 2012)	0.62
"014) compared to the dosing of two capsules of (dose equivalent) 75% drug-loaded SNEDDS."	( Supersaturated self-nanoemulsifying drug delivery systems (Super-SNEDDS) enhance the bioavailability of the poorly water-soluble drug simvastatin in dogs. Garmer, M; Holm, R; Karlsson, JJ; Müllertz, A; Rades, T; Thomas, N, 2013)	0.59
" An additional aim is to assess the effect of the polypill on LDL-c and BP compared to the administration of separate pills of identically dosed components of the polypill."	( The evening versus morning polypill utilization study: the TEMPUS rationale and design. Bots, ML; Grobbee, DE; Lafeber, M; Rodgers, A; Spiering, W; Thom, S; Visseren, FL; Webster, R, 2014)	0.4
"5 mg) in the evening; (2) the polypill in the morning; and (3) the use of the identically dosed agents in separate pills taken at different time points during the day."	( The evening versus morning polypill utilization study: the TEMPUS rationale and design. Bots, ML; Grobbee, DE; Lafeber, M; Rodgers, A; Spiering, W; Thom, S; Visseren, FL; Webster, R, 2014)	0.4
" Moreover, inappropriate statin dosing restrictions (underdosing of simvastatin and lovastatin) were deliberately utilized in PLATO, potentially contributing to the beneficial effect of ticagrelor."	( Exploring the ticagrelor-statin interplay in the PLATO trial. Dinicolantonio, JJ; Serebruany, VL, 2013)	0.63
" Without the appropriate dosage of simvastatin, the therapeutic effects on bone growth will be significantly reduced."	( The effectiveness of the controlled release of simvastatin from β-TCP macrosphere in the treatment of OVX mice. Ben-Nissan, B; Chou, J; Ito, T; Milthorpe, B; Otsuka, M, 2016)	0.97
" The results showed that a major component of the cytotoxicity of therapeutic levels of etoposide is mediated by gap junctions composed of connexin 43(Cx43) and simvastatin at the dosage which does not induce cytotoxicity enhances etoposide toxicity by increasing gap junction coupling."	( Simvastatin-induced up-regulation of gap junctions composed of connexin 43 sensitize Leydig tumor cells to etoposide: an involvement of PKC pathway. Fu, Y; Peng, J; Tao, L; Wang, L; Wang, Q; Wu, D; Xu, C; Yu, M, 2013)	2.03
" Most of the patients on more potent statins were not advised by their cardiologists to change the type or dosage of statin, which was more common in patients on less potent statins."	( Prevalence and types of persistent dyslipidemia in patients treated with statins. Reiner, Ž; Tedeschi-Reiner, E, 2013)	0.39
" The results were better in patients treated with more potent statins and cardiologists advised them much less frequently to change the type and dosage of statin."	( Prevalence and types of persistent dyslipidemia in patients treated with statins. Reiner, Ž; Tedeschi-Reiner, E, 2013)	0.39
"Flexibility in the recommended dosing time for a statin may improve patient compliance."	( Efficacy and safety of morning versus evening dose of controlled-release simvastatin tablets in patients with hyperlipidemia: a randomized, double-blind, multicenter phase III trial. Cho, SW; Han, KR; Hoon Park, S; Hyun, MS; Kim, MK; Kim, SH; Kim, YK; Seo, HS, 2013)	0.62
" We leveraged electronic medical records (EMRs) to extract potency (ED50) and efficacy (Emax) of statin dose-response curves and tested them for association with 144 preselected variants."	( Characterization of statin dose response in electronic medical records. Berg, RL; Davis, RL; Denny, JC; Feng, Q; Iwuchukwu, OF; Jiang, L; Jiang, M; Krauss, RM; McCarty, CA; Nickerson, DA; Peissig, PL; Roden, DM; Rotter, JI; Waitara, MS; Wei, WQ; Wilke, RA; Xu, H, 2014)	0.4
"Simvastatin has low aqueous solubility resulting in low oral bioavailability (5%) and thus presents a challenge in formulating a suitable dosage form."	( Preparation and characterization of Simvastatin solid dispersion using skimmed milk. Banerjee, SK; Behera, AL; Gaikwad, DD; Harer, SL; Sonar, PA, 2015)	2.13
" Patients prescribed simvastatin before June 8, 2011, requiring dosage adjustment based on labeling changes were evaluated for study inclusion."	( Impact of pharmacists' interventions and simvastatin dose restrictions. Barlow, PB; Farland, MZ; Franks, AS; Shoulders, BR; Williams, JD, 2014)	0.99
"Following FDA labeling changes for simvastatin, patient-specific recommendations made by pharmacists correlated with a greater likelihood of appropriate simvastatin dosing compared with a one-time didactic education session."	( Impact of pharmacists' interventions and simvastatin dose restrictions. Barlow, PB; Farland, MZ; Franks, AS; Shoulders, BR; Williams, JD, 2014)	0.95
" The osteogenic effect of simvastatin-loaded bone cement was in a critical sized defect in vivo to test the hypothesis the biologic response would be different depending on the dosage of simvastatin applied to bone cement."	( The effect of simvastatin-loaded polymeric microspheres in a critical size bone defect in the rabbit calvaria. Coelho, PG; Galli, S; Ichikawa, T; Jimbo, R; Kozai, Y; Naito, Y; Ozeki, T; Tagami, T; Terukina, T; Vandeweghe, S, 2014)	1.06
" 18/49 HNSCC qualified for FLAVINO-based dose-response analyses, and Sim significantly suppressed CF in 18/18 primary HNSCC."	( Simvastatin suppresses head and neck squamous cell carcinoma ex vivo and enhances the cytostatic effects of chemotherapeutics. Aigner, A; Boehm, A; Dietz, A; Mozet, C; Stoehr, M; Wichmann, G, 2014)	1.85
" Experimental time and dosage effects were observed for most bone values in the study group."	( Topical application of slow-release simvastatin as a bone substitute in bone defects in the rat tibia: a pilot study. Alterman, M; Casap, N; Friedman, M; Laviv, A; Rushinek, H; Weiss, EI, )	0.41
" Dosage and the methodology of administration require further calibration."	( Topical application of slow-release simvastatin as a bone substitute in bone defects in the rat tibia: a pilot study. Alterman, M; Casap, N; Friedman, M; Laviv, A; Rushinek, H; Weiss, EI, )	0.41
" The geometric mean AUC0-24h ratio of simvastatin acid for the two combined dosing regimens (B/C) and 90% confidence interval were 111% (102-121)."	( Pharmacokinetic interaction between simvastatin and fenofibrate with staggered and simultaneous dosing: Does it matter? Ansquer, JC; Aubonnet, P; Beckmann, K; Driessen, S; Lehnick, D; Mihara, K; Olbrich, M; Piskol, G; van Amsterdam, P; van Assche, H; Winsemius, A, 2014)	0.95
" After the dosing period of 8 days the animals were sacrificed and the blood was collected for the analysis of ST, its active metabolite simvastatin acid (STA), total cholesterol, triglyceride and liver enzymes including aspartate transaminase and alanine transaminase."	( Effect of vitamin D on bioavailability and lipid lowering efficacy of simvastatin. Al-Asmari, AK; Al-Eid, A; Al-Omani, SF; Al-Sabaan, F; Tariq, M; Ullah, Z, 2015)	0.85
" Statins exhibit a class-wide side effect of muscle toxicity and weakness, which has led regulators to impose both dosage limitations and a recall."	( Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review. Austin, MA; Canestaro, WJ; Thummel, KE, 2014)	0.4
" However, further studies to identify the optimal statin and dosing are required."	( Simvastatin increases the in vivo activity of the first-line tuberculosis regimen. Bruiners, N; Gennaro, ML; Karakousis, PC; Pine, R; Pinn, ML; Skerry, C, 2014)	1.85
" The described method was robust and successfully applied in quality control laboratories for routine analysis to determine the butylhydroxyanisol and simvastatin with its impurities content in tablet dosage forms."	( Development and validation of a reversed-phase HPLC method for simultaneous analysis of butylhydroxyanisol, simvastatin and its impurities in tablet dosage forms. Amood A L-Kamarany, M; Azougagh, M; Bouchafra, H; Bouklouze, A; Cherrah, Y; El Karbane, M, 2014)	0.81
" Pregnant Sprague Dawley rats were dosed orally with SMV, dipentyl phthalate (DPeP), or SMV plus DPeP from gestational days 14-18, and fetuses were evaluated on GD18."	( Simvastatin and dipentyl phthalate lower ex vivo testicular testosterone production and exhibit additive effects on testicular testosterone and gene expression via distinct mechanistic pathways in the fetal rat. Beverly, BE; Foster, PM; Furr, JR; Gray, LE; Lambright, CS; McIntyre, BS; Sampson, H; Travlos, G; Wilson, VS, 2014)	1.85
" This article reviews updated FDA warnings on capping the dose of simvastatin, recent package insert labeling changes of particular statins that address combinations with potent cytochrome P450 inhibitors, and current renal dosing recommendations for statins."	( Avoiding patient morbidity: Updated statin drug interactions and risks for patient harm. Campbell, JD; Finks, SW, 2014)	0.64
"Opportunity to increase simvastatin dosing through education, prescribing targets and incentives."	( Quality and efficiency of statin prescribing across countries with a special focus on South Africa: findings and future implications. Bishop, I; Campbell, SM; Godman, B; Malmström, RE; Truter, I, 2015)	0.72
" In June 2011, the US FDA released a Drug Safety Communication that provided updated product labeling with dosing restrictions for simvastatin to minimize the risk of myopathies."	( Simvastatin prescribing patterns before and after FDA dosing restrictions: a retrospective analysis of a large healthcare claims database. Ghushchyan, V; Nair, K; Saseen, JJ; Tuchscherer, RM, 2015)	2.06
"Our objective was to describe prescribing patterns of simvastatin in combination with medications known to increase the risk of myopathies following updated product labeling dosing restrictions in June 2011."	( Simvastatin prescribing patterns before and after FDA dosing restrictions: a retrospective analysis of a large healthcare claims database. Ghushchyan, V; Nair, K; Saseen, JJ; Tuchscherer, RM, 2015)	2.11
" To improve dosing accuracy and facilitate the determination of dosing regimens in function of the body weight, the proposed study aims at preparing transdermal niosomal gels of simvastatin as possible transdermal drug delivery system for pediatric applications."	( Assessment of simvastatin niosomes for pediatric transdermal drug delivery. Ahmed, OA; Fahmy, UA; Hosny, KM; Zidan, AS, 2016)	0.99
"To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System (SUS) perspective."	( Cost-effectiveness of high, moderate and low-dose statins in the prevention of vascular events in the Brazilian public health system. Duncan, BB; Polanczyk, CA; Restelatto, LM; Ribeiro, RA; Stella, SF; Vieira, JL; Ziegelmann, PK, 2015)	0.42
" SMV dosage was set as control group and had two different dosages in this group on the basis of the concentration of SMV."	( [Effects of simvastatin nano-liposomes on osteogenic differentiation of bone marrow stromal cells]. Qi, R; Shen, WW; Wang, C; Xu, L, 2014)	0.78
" Compared with the same dosage of SMV in these groups, control group and experimental group had significantly elevated the specific activity of ALP, the staining of BCIP/NBTKit as well as the protein expression of BMP-2."	( [Effects of simvastatin nano-liposomes on osteogenic differentiation of bone marrow stromal cells]. Qi, R; Shen, WW; Wang, C; Xu, L, 2014)	0.78
" Dosing was designed to produce comparable low-density lipoprotein cholesterol reductions, while enabling assessment of potential simvastatin-associated pleiotropic effects."	( High-dose simvastatin exhibits enhanced lipid-lowering effects relative to simvastatin/ezetimibe combination therapy. D'Alexandri, FL; Fiehn, O; Grapov, D; Haeggström, JZ; Hyötyläinen, T; Newman, JW; Orešič, M; Pedersen, TL; Pernow, J; Settergren, M; Snowden, SG; Wheelock, CE, 2014)	1.01
" Further research is necessary to determine the optimal dosage and the safety of simvastatin."	( Reduction of epidural scar adhesion by topical application of simvastatin after laminectomy in rats. Cao, XJ; Li, XL; Liang, Y; Lu, C; Sun, Y; Yan, LQ, 2015)	0.88
" In addition, the reduced dosage rate of SMV-zein nanoparticles improves patient tolerability and compliance."	( Optimization of caseinate-coated simvastatin-zein nanoparticles: improved bioavailability and modified release characteristics. Ahmed, OA; Al-Sawahli, MM; Fahmy, UA; Hosny, KM, 2015)	0.7
" It is a major determinant of half-life and dosing frequency of a drug."	( Volume of Distribution in Drug Design. Beaumont, K; Di, L; Maurer, TS; Smith, DA, 2015)	0.42
" The administration of simvastatin also prevented the morphine-induced shift to the right of the 50% effective dose (ED50) in the dose-response curve."	( Simvastatin prevents morphine antinociceptive tolerance and withdrawal symptoms in rats. Ghasemi, F; Hassanzadeh, K; Izadpanah, E; Moloudi, MR; Moradi, A; Rahimmi, A, 2015)	2.17
" Low-density lipoprotein receptor-knockout (LDLR(-/-)) mice fed an atherogenic diet were dosed daily with H(2) and/or simvastatin."	( Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice. Jiao, P; Qin, S; Song, G; Sun, X; Tian, H; Tian, S; Wu, Y; Yao, S; Yu, Y; Zhai, L; Zhang, X; Zhang, Z; Zhao, H; Zong, C, 2015)	0.63
" The guideline identifies four cohorts of patients with proven benefits from statin therapy and streamlines the dosing and monitoring recommendations based on evidence from published, randomized controlled trials."	( Implementation of the 2013 American College of Cardiology/American Heart Association Blood Cholesterol Guideline Including Data From the Improved Reduction of Outcomes: Vytorin Efficacy International Trial. Dinkler, J; Watson, K; Ziaeian, B, 2015)	0.42
" Primary PK and PD parameters were AUCs on dosing days."	( Lack of Potential Pharmacokinetic and Pharmacodynamic Interactions Between Piragliatin, a Glucokinase Activator, and Simvastatin in Patients With Type 2 Diabetes Mellitus. Boldrin, M; Georgy, A; Liang, Z; Zhai, S; Zhi, J, 2016)	0.64
" All of the incorrect interpretations were for patients with test results indicating a dosing or drug change (6/19; 32%)."	( Community pharmacists' experience with pharmacogenetic testing. Haga, SB; Mills, R; Moaddeb, J, )	0.13
" Thus, the patch may serve as an alternative therapy to oral dosage form of simvastatin with outmost patient compliance."	( Application of Response Surface Methodology for Design and Optimization of Reservoir-type Transdermal Patch of Simvastatin. Parhi, R; Patnaik, S; Suresh, P, 2016)	0.88
" Thus, the film may serve as an alternative therapy to oral dosage form of SS."	( Formulation optimization and characterization of transdermal film of simvastatin by response surface methodology. Parhi, R; Suresh, P, 2016)	0.67
"In order to achieve better in-vivo performance of the final dosage form comprising a poorly soluble drug the physicochemical properties of the active pharmaceutical ingredient can be altered not only by changing the solid state form but also through the conversion of their crystal habits."	( Influence of Crystal Habit on the Dissolution of Simvastatin Single Crystals. Bukovec, P; Meden, A; Smrkolj, M; Vrečer, F, 2015)	0.67
" Model application can be of advantage for dosing adjustment to avoid serious adverse effects resulted from concomitant use of both drugs."	( Pharmacokinetic model for the inhibition of simvastatin metabolism by itraconazole. Chan-Im, D; Chiang-Ngernthanyakool, R; Lohitnavy, M; Methaneethorn, J; Phaohorm, S; Tongpeng, W, 2015)	0.68
" Duration and dosage of statin use were obtained from pharmaceutical claims."	( Statin use associated with a reduced risk of pneumonia requiring hospitalization in patients with myocardial infarction: a nested case-control study. Chang, YH; Chien, LN; Chuang, MT; Lin, CF; Liu, JC, 2016)	0.43
" After 6 months, a subset of HC rats began daily oral simvastatin dosing (HC+S) at 20 mg/kg."	( Effect of simvastatin on rat supraspinatus tendon mechanical and histological properties in a diet-induced hypercholesterolemia model. Soslowsky, LJ; Tucker, JJ, 2016)	1.09
" Controversial results between the in vivo studies are mostly due to the differences in the route of administration, dose, dosage and carrier type."	( Role of Simvastatin on fracture healing and osteoporosis: a systematic review on in vivo investigations. Moshiri, A; Oryan, A; Sharifi, AM, 2016)	0.87
" Concentrations required for effective simvastatin- or resveratrol-induced inhibition of mitochondrial respiration were found much higher than concentrations achieved under standard dosing of these drugs."	( Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration. Fišar, Z; Hroudová, J; Kopřivová, A; Macečková, D; Singh, N, 2016)	1.11
" No significant associations were observed in dose-response analyses or in analysis of all-cause mortality."	( Statin use and breast cancer survival: a nationwide cohort study in Scotland. Cardwell, CR; Hughes, CM; Mc Menamin, ÚC; Murray, LJ, 2016)	0.43
" This work aimed at developing an innovative solid dosage form for oral administration based on tableting nanostructured lipid carriers (NLC), coated with conventional polymer agents."	( Can lipid nanoparticles improve intestinal absorption? Arnaut, LG; Mendes, M; Pais, AACC; Soares, HT; Sousa, JJ; Vitorino, C, 2016)	0.43
" We considered any type and dosage of statin as eligible, as long as the control and experimental arms differed only in the timing of the administration of the same statin."	( Chronotherapy versus conventional statins therapy for the treatment of hyperlipidaemia. Añino Alba, A; Fernandez-Esteban, I; Fernandez-Tabera, JM; Gómez Álvarez, P; Izquierdo-Palomares, JM; Martin-Carrillo, P; Pinar López, Ó; Plana, MN; Saiz, LC, 2016)	0.43
" In vivo, low continuous dosing of ezetimibe, delivered by food, or simvastatin, delivered via an osmotic pump had no effect on tumor growth compared to control mice."	( Evidence for Feedback Regulation Following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model. Alfaqih, MA; Barry, WT; Dambal, SK; Dewhirst, MW; Freedland, AR; Freedland, SJ; Freeman, MR; Macias, E; Masko, EM; Muehlbauer, MJ; Newgard, CB; Phillips, TE; Pizzo, SV; Poulton, SH; Sanders, SE; Solomon, KR; Sun, S; Valilis, NA, 2017)	0.69
" Electronic pharmacy records were used to abstract information on the type, length, and dosage of statin exposures starting in the year prior to diagnosis."	( Influence of Statins and Cholesterol on Mortality Among Patients With Pancreatic Cancer. Chang, JI; Huang, BZ; Li, E; Wu, BU; Xiang, AH, 2017)	0.46
" Vitamin D (25-OHD) dosing was performed by chemiluminescence method through the LIAISON® Vitamin D assay (Diasorin Inc)."	( Impact of high-dose statins on vitamin D levels and platelet function in patients with coronary artery disease. Barbieri, L; Bellomo, G; Daffara, V; De Luca, G; Marino, P; Nardin, M; Pergolini, P; Rolla, R; Schaffer, A; Suryapranata, H; Verdoia, M, 2017)	0.46
" Also, preoperative adjustment of statin dosage may be recommended."	( Laparoscopic partial nephrectomy in a patient on simvastatin : Delayed recovery from neuromuscular blockade. Abd El-Hakeem, EE; Almazlom, SA; Alsayyad, AJ; Kaki, AM, 2017)	0.71
" When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose."	( Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs. Awasthi, R; Dhiman, N; Dua, K; Jindal, S; Khatri, S, )	0.13
"Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms."	( Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs. Awasthi, R; Dhiman, N; Dua, K; Jindal, S; Khatri, S, )	0.37
" Metformin hydrochloride (MTF), sitagliptin phosphate (SIT), simvastatin (SIM) and ezetimibe (EZB) were simultaneously determined with a simple reversed-phase LC method in which a SIT-SIM binary mixture, present in a dosage form brand, was considered central for its development."	( A Versatile Liquid Chromatographic Method for the Simultaneous Determination of Metformin, Sitagliptin, Simvastatin, and Ezetimibe in Different Dosage Forms. El-Zaher, AA; Elkady, EF; Elwy, HM; Saleh, MAEM, 2018)	0.94
"Chemometric spectrophotometric methods have been developed in the present study for the simultaneous determination of simvastatin and nicotinic acid in their synthetic binary mixtures and in their mixtures with possible excipients present in tablet dosage form."	( Development and Validation of Chemometric Spectrophotometric Methods for Simultaneous Determination of Simvastatin and Nicotinic Acid in Binary Combinations. Alahmad, S; Elfatatry, HM; Hammad, SF; Mabrouk, MM; Mansour, FR, 2018)	0.9
" The developed SV-specific PBPK model could potentially be used to assess the influence of formulation factors on drug absorption and disposition when developing SV oral dosage forms."	( In vitro/in silico approach in the development of simvastatin-loaded self-microemulsifying drug delivery systems. Ćetković, Z; Cvijić, S; Vasiljević, D, 2018)	0.73
" Therefore, the combination of low dosage simvastatin and NF-PLLA scaffolds appears to be a promising strategy for dentin regeneration with inflamed dental pulp tissue, by minimizing the inflammatory reaction and increasing the regenerative potential of resident stem cells."	( Simvastatin and nanofibrous poly(l-lactic acid) scaffolds to promote the odontogenic potential of dental pulp cells in an inflammatory environment. de Souza Costa, CA; Eyster, TW; Ma, PX; Mohamed, F; Soares, DG; Zhang, Z, 2018)	2.19
"First, we performed a dose-response assay to select the bioactive dose of SIM capable of inducing an odontoblastic phenotype in dental pulp cells (DPCs); after which we evaluated the synergistic effect of this dosage with the CHSC/DPC construct."	( Biological Analysis of Simvastatin-releasing Chitosan Scaffold as a Cell-free System for Pulp-dentin Regeneration. Anovazzi, G; Basso, FG; Bordini, EAF; de Souza Costa, CA; Hebling, J; Silva Leite, MLA; Soares, DG; Zuta, UO, 2018)	0.79
" Globally, SIM induced several effects that did not follow a dose-response relationship; embryonic development, biochemical and molecular markers, were significantly impacted in the lower concentrations, 8 ng/L, 40 ng/L and/or 200 ng/L, whereas no effects were recorded for the highest tested SIM levels (1000 ng/L)."	( Chronic environmentally relevant levels of simvastatin disrupt embryonic development, biochemical and molecular responses in zebrafish (Danio rerio). André, A; Barros, S; Capitão, A; Montes, R; Neuparth, T; Quintana, JB; Rodil, R; Santos, MM; Soares, J, 2018)	0.74
"We observed that a low dosage of simvastatin accelerated cell proliferation , whereas its high dosage (>15 μg/mL) suppressed propagation."	( Simvastatin increases cell viability and suppresses the expression of cytokines and vascular endothelial growth factor in inflamed human dental pulp stem cells in vitro. Gong, Z; Li, X; Qiu, Y; Xue, D; Zhu, F, 2018)	2.2
"Fifty-two patients in the CYP3A study (pharmacokinetic [PK] analysis, n = 49), and 44 patients in the BCRP study were dosed (PK analysis, n = 44)."	( Effect of multiple-dose osimertinib on the pharmacokinetics of simvastatin and rosuvastatin. Aransay, NR; Arkenau, T; Bui, K; Dickinson, PA; Harvey, RD; Isambert, N; Lee, JS; So, K; Thomas, K; Vansteenkiste, J; Vishwanathan, K; Weilert, D, 2018)	0.72
"All patients with age ≤75 years undergoing PCI between January 2011 and May 2016 at an urban, tertiary care center and discharged with available statin dosage data were included."	( Temporal trends, determinants, and impact of high-intensity statin prescriptions after percutaneous coronary intervention: Results from a large single-center prospective registry. Aquino, M; Baber, U; Barman, N; Camaj, A; Chandrasekhar, J; Claessen, B; Dangas, G; Faggioni, M; Farhan, S; Guedeney, P; Kalkman, DN; Kini, A; Kovacic, JC; Mehran, R; Moreno, P; Shah, S; Sharma, S; Sorrentino, S; Sweeny, J; Vijay, P; Vogel, B, 2019)	0.51
"The drug in a solid dosage form must undergo dissolution before it is available for absorption from the gastrointestinal tract."	( Liquisolid systems: Understanding the impact of drug state (solution or dispersion), nonvolatile solvent and coating material on simvastatin apparent aqueous solubility and flowability. Anzilaggo, D; O'Reilly Beringhs, A; Pezzini, BR; Sonaglio, D; Stulzer, HK, 2019)	0.72
" The optimal drug dosage was determined by examining the proliferative activity and ALP activity of the MG63 cells."	( The role of the ERK1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in MG63 cells. Feng, X; Niu, M; Zhou, L, 2018)	0.76
" The results of this study confirmed that a simple method of extrusion-spheronization can be employed to enhance the dissolution of simvastatin in multi particulates dosage form which can also be employed for other poorly water-soluble drugs."	( Synergistic effect of polyethylene glycol and superdisintegrant on dissolution rate enhancement of simvastatin in pellet formulation. Afrasiabi Garekani, H; Aftabi, SF; Javidi, M; Nia, FF; Nokhodchi, A; Sadeghi, F, 2019)	0.93
" This joint simvastatin metabolite model is envisaged to facilitate optimisation of simvastatin dosing in children/adolescents."	( A population pharmacokinetic model for simvastatin and its metabolites in children and adolescents. Abdel-Rahman, S; Galetin, A; Leeder, JS; Ogungbenro, K; Wagner, JB, 2019)	1.16
" Our findings contribute towards the design of controlled release with low drug dosing bone grafts: i-CPFs loaded with PITA as osteogenic and angiogenic agent."	( Injectable calcium phosphate foams for the delivery of Pitavastatin as osteogenic and angiogenic agent. Canal, C; Ginebra, MP; Guillem-Marti, J; Khurana, K; Mücklich, F; Soldera, F, 2020)	0.56
" Those who terminated statin medication or reduced statin dosage had a higher mortality (34% and 20%, respectively; P < 0."	( Adherence to statin therapy favours survival of patients with symptomatic peripheral artery disease. Adam, L; Baumgartner, I; Dopheide, JF; Drexel, H; Kaspar, M; Papac, L; Ramadani, H; Rastan, A; Veit, J; Vonbank, A, 2021)	0.62
" Low-density lipoprotein cholesterol (LDL-C) levels and intensity of statin therapy (based on dosage and type of statin) were assessed from all available hospital records."	( Treatment Patterns of Lipid-Lowering Therapy in Patients with Coronary Artery Disease Aged Above and Below 75 Years: A Retrospective Cross-Sectional Study of 1500 Patients in a Tertiary Care Referral Center in Germany. Al-Rashid, F; Dykun, I; Hendricks, S; Jánosi, RA; Mahabadi, AA; Rassaf, T; Totzeck, M; Wiefhoff, D, 2020)	0.56
" The present study demonstrated that there was an association between the therapeutic effect and dosage of simvastatin within a definitive range."	( Effects of simvastatin on iNOS and caspase‑3 levels and oxidative stress following smoke inhalation injury. Chang, C; Cui, ZJ; Gao, Y; Guo, PF; Khan, I; Ma, Z; Meng, QN; Wang, XB; Yang, RQ, 2020)	1.16
" Due to MI alone, simvastatin dosage was reduced in 23."	( Safety of Chronic Simvastatin Treatment in Patients with Decompensated Cirrhosis: Many Adverse Events but No Liver Injury. Álvarez, D; Cartier, M; Marino, M; Míguez, C; Muñoz, AE; Pollarsky, F; Romero, G; Salgado, P; Vázquez, H, 2021)	1.29
"Chronic treatment with simvastatin 40 mg/day in patients with decompensated cirrhosis was associated with several adverse events, being MI the only clinically significant one, which appears to be related to the simvastatin dosage and the degree of cirrhosis severity."	( Safety of Chronic Simvastatin Treatment in Patients with Decompensated Cirrhosis: Many Adverse Events but No Liver Injury. Álvarez, D; Cartier, M; Marino, M; Míguez, C; Muñoz, AE; Pollarsky, F; Romero, G; Salgado, P; Vázquez, H, 2021)	1.27
" Simvastatin therapy for 6 months in patients with the initial stage of heart failure at a daily dosage of 20 mg does not impair glomerular function in the form of reduced glomerular filtration rate (GFR)."	( Сhanges in the functional state of the epithelium of the proximal renal tubules in patients with the initial stage of chronic heart failure during simvastatin therapy. Kopylov, VY, 2020)	1.67
" Most importantly, benefit from the effective in situ calcium supplement and targeted Sim delivery, this therapeutic regime (TMA/Sim) achieved better synergetic effects than conventional combination strategies with promising osteoporosis reversion performance under low calcium dosage (1/10 of commercial calcium carbonate tablet) and significantly attenuated side effects."	( Water/pH dual responsive in situ calcium supplement collaborates simvastatin for osteoblast promotion mediated osteoporosis therapy via oral medication. Hu, F; Lv, J; Song, Y; Tao, S; Wang, C; Yu, F; Yuan, H; Zhao, R; Zhou, W, 2021)	0.86
" Because physiologically based pharmacokinetic (PBPK) modeling has demonstrated to be a valuable tool to improve pharmacotherapy affected by DDIs or DGIs, it might also be useful for precision dosing in extensive interaction network scenarios."	( Physiologically Based Precision Dosing Approach for Drug-Drug-Gene Interactions: A Simvastatin Network Analysis. Lehr, T; Schwab, M; Selzer, D; Wojtyniak, JG, 2021)	0.85
" Only rosuvastatin was assessed in a repeated dosing PK study."	( A systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis. Abraldes, JG; Al-Karaghouli, M; Cabrera Garcia, L; Kalainy, S; Sung, S, 2021)	0.62
" Because pharmacodynamic interaction between statins and bempedoic acid is complex, a dose-response model was developed to predict LDL-C pharmacodynamics following administration of statins combined with bempedoic acid."	( Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose-response model. Amore, BM; Barrett, PHR; Catapano, AL; Chapel, S; Crass, RL; Emery, MG; Jadhav, SB; Kerschnitzki, M; Sasiela, WJ; Watts, GF, 2022)	0.72
"Bempedoic acid and statin dosing and LDL-C data were pooled from 14 phase 1-3 clinical studies."	( Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose-response model. Amore, BM; Barrett, PHR; Catapano, AL; Chapel, S; Crass, RL; Emery, MG; Jadhav, SB; Kerschnitzki, M; Sasiela, WJ; Watts, GF, 2022)	0.72
" However, because of its narrow therapeutic index, dosing can be challenging."	( Stable warfarin dose prediction in sub-Saharan African patients: A machine-learning approach and external validation of a clinical dose-initiation algorithm. Asiimwe, IG; Blockman, M; Cohen, K; Cupido, C; Hutchinson, C; Jacobson, B; Jorgensen, AL; Lamorde, M; Morgan, J; Mouton, JP; Nakagaayi, D; Okello, E; Pirmohamed, M; Schapkaitz, E; Sekaggya-Wiltshire, C; Semakula, JR; Waitt, C; Zhang, EJ, 2022)	0.72
" Among the two technologies, fluid bed layering provided dry emulsion products with higher relative bioavailability and better product characteristics for further processing into final dosage forms."	( Relative bioavailability enhancement of simvastatin via dry emulsion systems: Comparison of spray drying and fluid bed layering technology. Aguiar Zdovc, J; Dreu, R; Gosenca Matjaž, M; Grabnar, I; Mravljak, J; Pohlen, M; Snoj, T; Trontelj, J, 2022)	0.99
" Ten patients were instructed to interrupt simvastatin dosing and return for blood sampling for the subsequent 3 days."	( Monitoring Simvastatin Adherence in Patients With Coronary Heart Disease: A Proof-of-Concept Study Based on Pharmacokinetic Measurements in Blood Plasma. Andersen, AM; Bergan, S; Fagerland, MW; Husebye, E; Kristiansen, O; Munkhaugen, J; Vethe, NT, 2022)	1.37
" Peak and trough drug plasma concentrations were collected based on the dosing interval and pharmacokinetics of the drugs and quantified using high performance liquid chromatography."	( Simvastatin, but Not Atorvastatin, Is Associated with Higher Peak Rivaroxaban Serum Levels and Bleeding: an Asian Cohort Study from Singapore. Chan, ECY; Soh, XQ; Tan, DS, 2023)	2.35
" Here, four-week-old mice expressing KrasG12D in all pancreatic lineages (KC mice) and fed an obesogenic high fat, high calorie diet that promotes early PDAC development were randomized onto low dosage metformin, simvastatin, or both drugs in combination administered orally."	( Low dosage combination treatment with metformin and simvastatin inhibits obesity-promoted pancreatic cancer development in male KrasG12D mice. Eibl, G; Hines, OJ; Lugea, A; Pandol, SJ; Rozengurt, E; Sinnett-Smith, J; Sun, X; Teper, Y; Waldron, RT; Ye, L, 2023)	1.35
" The most optimal simvastatin cubosomal formulation was then included in a cubogel dosage form using different gelling agents."	( Formulation and evaluation of simvastatin cubosomal nanoparticles for assessing its wound healing effect. Ahmed, LM; Elfaham, TH; Hassanein, KMA; Mohamed, FA, 2023)	1.53