valproic acid

Research Excerpts

Overview

Valproic acid (VPA, 1) is a major broad spectrum antiepileptic and central nervous system drug. It is widely used to treat epilepsy, bipolar disorder, and migraine. Its use is limited by two life-threatening side effects: teratogenicity and hepatotoxicity.

Excerpt	Reference	Relevance
"Valproic acid (VPA) is a major antiepileptic drug (AED); however, its use is limited by two life-threatening side effects: teratogenicity and hepatotoxicity. "	( Potent anticonvulsant urea derivatives of constitutional isomers of valproic acid. Bialer, M; Finnell, RH; Shimshoni, JA; Wlodarczyk, B; Yagen, B, 2007)	2.02
"Valproic acid (VPA, 1) is a major broad spectrum antiepileptic and central nervous system drug widely used to treat epilepsy, bipolar disorder, and migraine. "	( Synthesis and evaluation of antiallodynic and anticonvulsant activity of novel amide and urea derivatives of valproic acid analogues. Bialer, M; Devor, M; Kaufmann, D; Shimshoni, JA; Yagen, B, 2009)	2.01
"Valproic acid (VPA) is an anticonvulsant agent prescribed for the treatment of epilepsy and seizure."	( Valproic acid suppresses cuprizone-induced hippocampal demyelination and anxiety-like behavior by promoting cholesterol biosynthesis. Gan, G; He, Y; Hu, Y; Liu, X; Yang, J; Yao, Y; Zhang, A; Zhang, C; Zhu, X, 2021)	2.79
"Valproic acid (VPA) is an approved drug for managing epileptic seizures, bipolar disorders, and migraine. "	( Hidden pharmacological activities of valproic acid: A new insight. Ahmed, AF; Gupta, S; Morsy, MA; Nair, AB; Singh, D; Verma, I, 2021)	2.34
"Valproic acid (VPA) is a drug used to treat epilepsy, bipolar disorders and headaches. "	( Valproic acid during pregnancy decrease the number of spermatogenic cells and testicular volume in the offspring of mice: Stereological quantification. Conei, D; Risopatrón, J; Rojas, M; Santamaría, L, 2021)	3.51
"Valproic acid (VPA) is an antiepileptic drug found to induce mitochondrial dysfunction and autophagy in cancer cell lines. "	( Acute Valproate Exposure Induces Mitochondrial Biogenesis and Autophagy with FOXO3a Modulation in SH-SY5Y Cells. Jang, EH; Kim, SA; Lee, JH, 2021)	2.06
"Valproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. "	( Effect of CYP2C19 polymorphisms on serum valproic level acid in Chinese Han patients with schizophrenia. Ju, X; Li, J; Liu, J; Shi, J; Song, M; Wang, C; Wang, S; Yan, P, 2021)	2.06
"Valproic acid (VPA) is an antiepileptic drug with a pronounced teratogenic effect associated with a high risk of ASD, and its administration to rats during the gestation is used for autism modeling."	( Assessment of behavioral, morphological and electrophysiological changes in prenatal and postnatal valproate induced rat models of autism spectrum disorder. Chavushyan, V; Danielyan, M; Fereshetyan, K; Yenkoyan, K, 2021)	1.34
"Valproic acid (VPA) is a well-established anticonvulsant drug discovered serendipitously and marketed for the treatment of epilepsy, migraine, bipolar disorder and neuropathic pain. "	( Insights into Structural Modifications of Valproic Acid and Their Pharmacological Profile. Bora, S; Hasija, Y; Kukal, S; Kukreti, R; Kukreti, S; Mishra, MK; Muthusamy, K; Paul, PR; Saso, L; Singh, A, 2021)	2.33
"Valproic acid (VPA) is a frequently prescribed anti-epileptic drug. "	( Assessment of need for hemostatic evaluation in patients taking valproic acid: A retrospective cross-sectional study. Beckers, EAM; Henskens, YMC; Heubel-Moenen, FCJI; Klinkenberg, S; Post, DS; Rijkers, K; Schijns, OEMG; van der Veer, A; van Kranen-Mastenbroek, VHJM; Verhezen, PWM; Wagner, GL; Willems, PCPH, 2022)	2.4
"Valproic acid (VPA) is a well-known histone deacetylase inhibitor (HDACi), which due to its epigenetic focus needs to be studied in depth to understand the effects it might elicit in BC cells."	( Untargeted LC-MS/MS Metabolomics Study on the MCF-7 Cell Line in the Presence of Valproic Acid. Bakalara, N; Correa-Basurto, J; Estrada-Pérez, AR; Fromager, B; García-Vázquez, JB; Rosales-Hernández, MC, 2022)	1.67
"Valproic acid (VPA) is a widely used antiepileptic drug not recommended in pregnancy because it is teratogenic. "	( Transcriptome meta-analysis of valproic acid exposure in human embryonic stem cells. Gomes, JDA; Kowalski, TW; Lord, VO; Mariath, LM; Recamonde-Mendoza, M; Sgarioni, E; Vianna, FSL, 2022)	2.45
"Valproic acid (VPA) is a drug used for the treatment of epilepsy, seizures, migraines, and bipolar disorders. "	( Valproic Acid-Induced Anxiety and Depression Behaviors are Ameliorated in p39 Cdk5 Activator-Deficient Mice. Ando, K; Hisanaga, SI; Kawakami, A; Ohshima, T; Takahashi, M; Takasugi, T; Wei, R, 2022)	3.61
"Valproic acid (VPA) is a HDACI that shows promising chemotherapeutic effect in a number of tumor cells."	( Enhanced antitumor activity of combined methotrexate and histone deacetylase inhibitor valproic acid on mammary cancer in vitro and in vivo. Badary, OA; El Said, HH; El-Khatib, AS; Elmazar, MM; Shouman, SA, 2022)	1.67
"Valproic acid (VPA) is a widely prescribed drug to treat epilepsy, bipolar disorder, and migraine. "	( Aberrant induction of p19Arf-mediated cellular senescence contributes to neurodevelopmental defects. Keyes, WM; Klein, A; Knauer-Meyer, T; Plassat, JL; Rhinn, M; Zapata-Bodalo, I, 2022)	2.16
"Valproic acid (VA) is a proven inhibitor of human histone deacetylases (HDACs). "	( Evaluation of the inhibitory potential of Valproic acid against histone deacetylase of Chandra, S; Joshi, T; Pant, M; Prasanna, P; Pundir, H, )	1.84
"Valproic acid (VPA) is a clinically used antiepileptic drug, but it is associated with a significant risk of a low verbal intelligence quotient (IQ) score, attention-deficit hyperactivity disorder and autism spectrum disorder in children when it is administered during pregnancy. "	( A CCR5 antagonist, maraviroc, alleviates neural circuit dysfunction and behavioral disorders induced by prenatal valproate exposure. Honda, T; Ishihara, N; Ishihara, Y; Itoh, K; Namba, K; Taketoshi, M; Tominaga, T; Tominaga, Y; Tsuji, M; Vogel, CFA; Yamazaki, T, 2022)	2.16
"Valproic acid is a frequently used antiepileptic drug and known pediatric hepatotoxic agent. "	( Potential of the zebrafish (Danio rerio) embryo test to discriminate between chemicals of similar molecular structure-a study with valproic acid and 14 of its analogues. Braunbeck, T; Brotzmann, K; Escher, SE; Walker, P, 2022)	2.37
"Valproic acid (VPA) is a well-known drug prescribed as anti-epileptic. "	( Valproic acid determination by liquid chromatography coupled to mass spectrometry (LC-MS/MS) in whole blood for forensic purposes. Barone, R; Fais, P; Giorgetti, A; Pascali, JP; Pelletti, G, 2023)	3.8
"Valproic acid (VPA) is an anti-seizure drug that causes idiosyncratic liver injury. "	( Valproic acid induced liver injury: An insight into molecular toxicological mechanism. Ezhilarasan, D; Mani, U, 2022)	3.61
"Valproic acid (VPA) is a common antiepileptic drug that is also used routinely for various psychiatric disorders. "	( Valproic Acid Overdose: Case Report and Literature Review. Berezowski, I; Frasure, SE; Mazer-Amirshahi, M; Patel, J; Pourmand, A; Tran, QK, 2022)	3.61
"Valproic acid (VPA) is an effective first-line anticonvulsant that is associated with several side effects including bone marrow suppression and subsequent cytopenia. "	( Valproic Acid Induced Thrombocytopenia and Dysmegakaryopoiesis in a Pediatric Patient. Akgun, Y; Baykara, Y; Langlie, J; Poveda, J; Van Truong, L, 2022)	3.61
"Valproic acid (VPA) is a widely used antiepileptic drug, and the herbal extract of Gastrodia elata exerts an anticonvulsant effect. "	( Neuroprotective effect and herbal-drug pharmacokinetic interaction of Gastrodia elata extract on valproic acid. Tsai, TH; Yang, L, 2022)	2.38
"Valproic acid (VPA) is a potential teratogenic agent, and prenatal exposure can cause autism-like symptoms including repetitive behaviors and defective sociability."	( Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model. Feng, Y; Gao, C; Guo, B; Huo, X; Jiang, S; Li, W; Liu, C; Sun, T; Sun, Y; Wang, A; Wang, C; Wang, F; Wang, Y; Xiao, L, 2022)	1.66
"Valproic acid (VPA) is a classic medication for several types of epilepsy and mood disorders, and some of its effectiveness and toxicity is associated with metabolites. "	( Determination of valproic acid and its six metabolites in human serum using LC-MS/MS and application to interaction with carbapenems in epileptic patients. Chen, R; Dong, L; Hu, N; Jiang, Y; Jiang, Z; Ling, J; Yang, X; Zou, S, 2023)	2.69
"Valproic acid is an effective mood stabilizer, registered for the treatment of bipolar disorder and epilepsy. "	( [A severe, reversible encephalopathy after prolonged use of valproic acid]. Bloemkolk, D; Gerritse, FL; Rundervoort, RS; van Haaren, PCF, 2023)	2.6
"Valproic acid (VPA) is a short-chain fatty acid widely prescribed in the treatment of seizure disorders and epilepsy syndromes, although its therapeutic value may be undermined by its toxicity. "	( Quantitative systems pharmacology Model to characterize valproic acid-induced hyperammonemia and the effect of L-carnitine supplementation. Fagiolino, P; Ibarra, M; Maldonado, C; Schiavo, A; Trocóniz, IF; Vázquez, M, 2023)	2.6
"Valproic acid (VPA) is an anti-epileptic drug used alone or in combination with other medications to treat seizures, mania, and bipolar disorder. "	( Sodium valproate exposure influences the expression of pparg in the zebrafish model. Benedetti, E; Caioni, G; Cimini, A; Merola, C; Perugini, M, 2023)	2.35
"Valproic acid (VPA) is an important and commonly used histone deacetylase (HDAC) inhibitor for class I (HDAC1, 2, 3, and 8) and class IIa (HDAC4, 5, 7, and 9)."	( Valproic Acid Inhibits Progressive Hereditary Hearing Loss in a KCNQ4 Variant Model through HDAC1 Suppression. Cho, HH; Choi, YM; Lee, S; Nam, YS, 2023)	3.07
"Valproic acid (VPA) is a known drug for treating epilepsy and mood disorders; however, it is not recommended for pregnant women because of its possible teratogenicity. "	( Neonatal Exposure to Valproate Induces Long-Term Alterations in Steroid Hormone Levels in the Brain Cortex of Prepubertal Rats. Cho, SH; Jang, EH; Kim, SA; Lee, J, 2023)	2.35
"Valproic acid (VA) is a clinically available histone deacetylase inhibitor with a well-documented side effect profile."	( Valproic acid radiosensitizes anaplastic thyroid cells through a decrease of the DNA damage repair capacity. Campos-Haedo, M; Cremaschi, G; Dagrosa, MA; Durán, HA; Grissi, C; Ibañez, IL; Juvenal, GJ; Oglio, R; Perona, M; Rosemblit, C; Thomasz, L; Villaverde, MS, 2023)	3.07
"Valproic acid (VPA) is an anticonvulsant drug that, when administered during pregnancy, causes various birth defects."	( Social deficits in mice prenatally exposed to valproic acid are intergenerationally inherited and rescued by social enrichment. Barrios, CD; Depino, AM; Zappala, C, 2023)	1.89
"Valproic acid (VPA) is a prevalent antiseizure medication (ASM) used to treat epilepsy. "	( Valproate-related hyperammonemic encephalopathy with generalized suppression EEG: a case report. Liu, X; Peng, X, 2023)	2.35
"Valproic acid (VPA) is a relatively safe drug widely used for the treatment of epileptic seizures and mania in bipolar disorder, as well as the prevention of migraine headaches. "	( Acute pancreatitis during valproic acid administration in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms: a case report. Harada, M; Hashimoto, R; Igata, R; Ikenouchi, A; Isomoto, N; Konishi, Y; Okamoto, N; Shinkai, T; Yanaga, M; Yoshimura, R, 2023)	2.65
"Valproic acid (VPA) is a well-documented contributor to liver injury, which is likely caused by the formation of its toxic metabolites. "	( Successful LC-MS/MS assay development and validation for determination of valproic acid and its metabolites supporting proactive pharmacovigilance. Chen, F; Dai, HR; Ding, XS; Guo, HL; Wang, J; Wang, WJ; Zhang, YY; Zhao, YT, 2023)	2.58
"Valproic acid (VPA) is a well-known anti-epileptic drug, but its prenatal exposure to animals causes social impairment, neurotransmitters imbalance, and neuroinflammation with ASD-like phenotypes."	( Syringic acid alleviates valproic acid induced autism via activation of p38 mitogen-activated protein kinase: Possible molecular approach. Mallan, S; Singh, S, 2023)	1.93
"Valproic acid (VPA) is an anti-epileptic medication that increases the risk of neural tube defect (NTD) outcomes in infants exposed during gestation. "	( Spatiotemporal protein dynamics during early organogenesis in mouse conceptuses treated with valproic acid. Colacino, JA; Harris, C; Lapehn, S, )	1.79
"Valproic acid (VPA) is a widely prescribed antiepileptic drug with various medicinal efficacies. "	( Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder. Azmai, MNA; Bakar, NA; Chong, SG; Fadzar, MSIM; Fahmi, MSAM; Faudzi, SMM; Hamid, NNAZZ; Ibrahim, WNW; Mastuki, SN; Norazhar, AI; Ramlan, NF; Saleh Hodin, NA; Zulkifli, AR, 2023)	2.62
"Valproic acid (VPA) is an effective drug, which is preferred for the treatments of epilepsy and various kinds of seizures. "	( The effects of valproic acid neurotoxicity on aggressive behavior in zebrafish autism model. Feng, T; Li, X; Lu, W, 2024)	3.24
"Valproic acid (VPA) is a widely used antiepileptic drug for epilepsy. "	( Association of UGT2B7 and CaMK4 with response of valproic acid in Chinese children with epilepsy. Li, Z; Wang, Y, )	1.83
"Valproic acid is an antiepileptic drug with more than 50 years of clinical use. "	( El ácido valproico como agente sensibilizador al tratamiento anticáncer. Correa-Basurto, J; Luna-Palencia, GR; Vásquez-Moctezuma, I, 2019)	1.96
"Valproic acid (VPA) is a anticonvulsant and mood-stabilizing agent used to treat epilepsy in patients of all ages. "	( Melatonin ameliorates sodium valproate-induced hepatotoxicity in rats. Buyuk, B; Coskun, O; Ovali, MA; Oztopuz, O; Sehitoglu, MH; Turkon, H; Uzun, M, 2020)	2
"Valproic acid (VPA) is a broad-spectrum antiepileptic drug indicated for monotherapy and adjunctive therapy of seizures, and complex manic episodes associated with bipolar disorder [1]. "	( Meropenem as an antidote for intentional valproic acid overdose. Priano, J; Smith, TL; Thomas, C, 2020)	2.27
"Valproic acid is a commonly used drug for many psychiatric disorders, particularly for epilepsy. "	( Ellagic acid attenuates liver toxicity induced by valproic acid in rats. Abdelkader, NF; Assaf, N; Elesawy, WH; Elyamany, M; Fawzy, HM; Gad, AM, 2020)	2.25
"Valproic acid (VPA) is a compound currently used in clinical practice for the treatment of epilepsy as well as bipolar and mood disorders. "	( Exploring the inhibitory activity of valproic acid against the HDAC family using an MMGBSA approach. Bello, M; Correa-Basurto, J; Sixto-López, Y, 2020)	2.27
"Valproic acid (VPA) is a widely used antiepileptic drugs. "	( Autophagy associated with the efficacy of valproic acid in PTZ-induced epileptic rats. Hu, L; Li, Q; Li, X; Li, Y; Li, Z; Lu, J; Tao, J; Wang, G; Wang, Y, 2020)	2.27
"Valproic acid (VPA) is a HDACI with reported controversial effects on the EMT."	( Evaluation of the Effects of Valproic Acid Treatment on Cell Survival and Epithelial-Mesenchymal Transition-Related Features of Human Gastric Cancer Cells. Jahani, M; Khanahmad, H; Nikpour, P, 2021)	1.63
"Valproic acid (VPA) is a frequently prescribed anti-epileptic drug which is known to cause liver toxicity and steatosis through mitochondrial dysfunction. "	( Valproic acid promotes mitochondrial dysfunction in primary human hepatocytes in vitro; impact of C/EBPα-controlled gene expression. Caiment, F; Kleinjans, J; Schrooders, Y; Smit, E; van den Beucken, T; Wolters, J, 2020)	3.44
"Valproic acid (VPA) is an effective drug, which is preferred for the treatments of epilepsy and various kinds of seizures. "	( Alpha-lipoic acid prevents brain injury in rats administered with valproic acid. Bilgin Sokmen, B; Turkyilmaz, IB; Yanardag, R, 2020)	2.24
"Valproic acid (VPA) is an anti-epileptic drug known to cause congenital craniofacial abnormalities, including orofacial clefts (OFC). "	( The anti-epileptic drug valproic acid causes malformations in the developing craniofacial skeleton of zebrafish larvae. Carels, CEL; Gebuijs, IGE; Metz, JR; Von den Hoff, JW; Wagener, FADTG; Zethof, J, 2020)	2.31
"Valproic acid (VPA) is a branched short-chain fatty acid primarily used in epilepsy, but is also used in bipolar disorder, migraine, and psychotic disorders. "	( Heart malformation is an early response to valproic acid in developing zebrafish. Anitha, V; Deepan, N; Ganesan, V; Jayaseelan, S; Kalaiselvan, D; Rajesh, V; Sivakumar, P, 2020)	2.26
"Valproic acid (VPA) is an HDAC inhibitor (HDACI) with an anticancer activity, but is hepatotoxic. "	( Epigenetic Evaluation of N-(2-hydroxyphenyl)-2-Propylpentanamide, a Valproic Acid Aryl Derivative with Activity Against HeLa Cells. Correa-Basurto, J; Luna-Palencia, GR; Meraz-Ríos, MA; Trujillo-Ferrara, J; Vásquez- Moctezuma, I, 2021)	2.3
"Valproic acid is an alternative treatment option."	( Prescribing Practices of Valproic Acid for Agitation and Delirium in the Intensive Care Unit. Duggal, A; Hohlfelder, B; Quinn, NJ; Torbic, H; Wanek, MR, 2021)	1.65
"Valproic acid (VPA) is a remarkably safe and effective antiepileptic drug."	( The changes of serum zinc, copper, and selenium levels in epileptic patients: a systematic review and meta-analysis. Boczek, T; Guo, F; He, Z; Hu, H; Jia, W; Kong, J; Shao, D; Song, Y; Tang, H; Wang, Y; Xia, L; Xu, X; Yang, L; Zhang, X, 2020)	1.28
"Valproic acid (VPA) is a broad spectrum anticonvulsant drug, which could be partially metabolised by cytochrome P450 (CYP) 2C9 and 2C19 enzymes. "	( Impact of CYP2C19 and CYP2C9 gene polymorphisms on sodium valproate plasma concentration in patients with epilepsy. Li, X; Liu, L; Mao, P; Song, C; Song, W; Zhang, Y, 2022)	2.16
"Valproic acid (VPA) is a potential pharmacologic agent that can be utilized to treat ICU delirium, though there is a paucity of evidence for its use, especially in patients with a history of substance abuse."	( Prolonged Refractory ICU Delirium Successfully Treated With Valproic Acid: Case Report and Literature Review. Louzon, PR; Masood, A; Recksieck, S; Subedi, B, 2021)	1.58
"Valproic acid (VPA) is a widely used anti-epileptic drug (AED) of demonstrated efficacy. "	( Risk-benefit assessment of treatment of epileptic women of childbearing age with valproic acid. Baraldés-Rovira, M; Gallego, Y; Mauri-Capdevila, G; Purroy, F; Quílez, A; Sanahuja, J, 2020)	2.23
"Valproic acid (VPA) is a drug commonly used for epileptic seizure control. "	( Valproic acid inhibits interferon-γ production by NK cells and increases susceptibility to Listeria monocytogenes infection. Chacón-Salinas, R; Chávez-Blanco, AD; Estrada-García, I; Estrada-Parra, S; Flores-Borja, F; Flores-Mejía, R; García-Pérez, BE; Serafín-López, J; Soria-Castro, R; Wong-Baeza, I, 2020)	3.44
"Valproic acid (VPA) is a broad-spectrum anticonvulsant drug. "	( The Effect of Sample Handling on Free Valproic Acid Levels. Babic, N; Bohm, N; Caddell, B; Champion-Lyons, E; Neyens, R; Wang, D, 2021)	2.34
"Valproic acid (VPA) is a branched short-chain fatty acid clinically used as a broad-spectrum antiepileptic drug in the treatment of neurological disorders, which has shown promising antiviral activity against some herpesviruses."	( Valproic Acid and Its Amidic Derivatives as New Antivirals against Alphaherpesviruses. Andreu, S; Bello-Morales, R; López-Guerrero, JA; Ripa, I, 2020)	2.72
"Valproic acid is a highly protein-bound drug."	( Valproic Acid-Induced Thrombocytopenia-Related Spontaneous Systemic Bleeding. Johnston, JP; Nerenberg, SF, 2020)	2.72
"Valproic acid (VPA) is a selective histone deacetylation (HDAC) inhibitor and exerts anti-cancer properties in different types of cancer. "	( Regulation of valproic acid induced EMT by AKT/GSK3β/β-catenin signaling pathway in triple negative breast cancer. Deveci Ozkan, A; Guney Eskiler, G; Kaleli, S; Ozbek Iptec, B; Ozman, Z; Sahin, E, 2021)	2.42
"Valproic acid (VA) is a drug widely used on the treatment of epilepsy and bipolar affective disorders, with stablished therapeutic concentration ranges in serum. "	( Simple determination of valproic acid serum concentrations using BioSPME followed by gas chromatography-mass spectrometric analysis. Antunes, MV; de Lima Feltraco Lizot, L; Hahn, RZ; Linden, R; Schaefer, VD; Schneider, A, 2021)	2.37
"Valproic acid is a medication most commonly used in the treatment of emotional and neurological depression, psychological imbalances, epilepsy, and bipolar disorder. "	( Protective Effect of Thyme Honey against Valproic Acid Hepatotoxicity in Wistar Rats. Boroujeni, MB; Omidipour, R; Rajabzadeh, A; Zarei, L, 2021)	2.33
"Valproic acid (VPA) is a broad-spectrum, antiepileptic drug, and it is also a potent teratogen."	( Emerging mechanisms of valproic acid-induced neurotoxic events in autism and its implications for pharmacological treatment. Fukunaga, K; Han, F; Lin, W; Meng, F; Naveed, M; Taleb, A; Xu, X; Zhang, G; Zhou, QG, 2021)	1.65
"Valproic acid (VPA) is a powerful antiepileptic drug that was associated with several neurological and hepatic problems especially with increasing its dose and duration. "	( Chronic valproic acid administration enhances oxidative stress, upregulates IL6 and downregulates Nrf2, Glut1 and Glut4 in rat's liver and brain. Abbas, KM; Awadalla, A; Elghaba, R; Helal, GM; Hussein, AM; Mokhtar, N; Othman, G; Sakr, HF, 2021)	2.5
"Valproic acid (VPA) is a well-known histone deacetylase inhibitor."	( A valproic acid-modified platinum diimine complex as potential photosensitizer for photodynamic therapy. Liu, Z; Wang, H; Zhang, Z, 2021)	2.06
"Valproic acid (VPA) is a teratogenic antiepileptic, causing alterations in oxidative stress in prenatal development, being altered the development of the male reproductive system. "	( Protective role of vitamin E in testicular development of mice exposed to valproic acid. Conei, D; Risopatrón, J; Rojas, M; Santamaría, L, 2021)	2.29
"Valproic acid (VPA) is a widely used antiepileptic drug for the treatment of epilepsy, seizures, and bipolar and psychiatric disorders. "	( Factors associated with blood carnitine levels in adult epilepsy patients with chronic valproic acid therapy. Miyaoka, H; Saito, M; Takizawa, T, 2021)	2.29
"Valproic acid is a carboxylic acid derivative commonly prescribed for several types of seizure disorders or for acute manic episodes in patients with bipolar disorder. "	( Clinical and pathophysiological characteristics of valproate-induced pleural effusion. Georgopoulou, A; Ismailos, G; Papadopoulou, E; Saroglou, M; Serasli, E; Tryfon, S; Vlachopoulos, D, 2021)	2.06
"Valproic acid (VPA) is an effective anti-epileptic drug clinically used to treat seizures, bipolar disorders and neuropathic pain in women of reproductive age. "	( Characterizing the effects of in utero valproic acid exposure on murine fetoplacental development. Shafique, S; Winn, LM, 2021)	2.33
"Valproic acid (VPA) is a widely prescribed broad-spectrum antiepileptic drug. "	( Influence of age and co-medication on the steady-state pharmacokinetics of valproic acid in Tunisian patients with epilepsy. Atheymen, R; Ben Mahmoud, L; Ghozzi, H; Hakim, A; Sahnoun, Z; Zeghal, K, 2017)	2.13
"Valproic acid (VPA) is a broad-spectrum antiepileptic drug, which is widely used as a first line treatment for idiopathic and symptomatic generalized epilepsy, as well as in non-epileptic psychiatric disorders in adult and pediatric patients. "	( The effect of VPA on bone: From clinical studies to cell cultures-The molecular mechanisms revisited. Pitetzis, DA; Spilioti, MG; Yavropoulou, MP; Yovos, JG, 2017)	1.9
"Valproic acid (VPA) is an anti-epileptic drug (AED) which is currently being investigated for its potential application in the treatment of several types of cancers, including solid and non-solid tumor. "	( Teratology of valproic acid: an updated review of the possible mediating mechanisms. Ponzano, A; Tiboni, GM, 2018)	2.28
"Valproic acid is a broad-spectrum anticonvulsant that has also gained attention in the psychiatric setting. "	( L-Carnitine supplementation to reverse hyperammonemia in a patient undergoing chronic valproic acid treatment: A case report. Fagiolino, P; Guevara, N; Maldonado, C; Silveira, A; Vázquez, M, 2017)	2.12
"Valproic acid (VPA) is an effective antiepileptic drug and mood stabilizer. "	( Monitoring Protein-Unbound Valproic Acid Serum Concentrations in Clinical Practice. de Jong, K; de Maat, M; Essink, G; Klok, B; Stalpers-Konijnenburg, S; van Erp, N; van Luin, M; Wallenburg, E, 2017)	2.19
"Valproic acid (VPA) is an antiepileptic drug, used for focal and generalized seizure. "	( The impact of valproic acid treatment on weight gain in pediatric patients with epilepsy. Battaglia, D; Blasi, V; DI Ruscio, F; Ferrara, P; Gatto, A, 2022)	2.52
"Valproic acid (VPA) is a widely prescribed medicine, and acute toxicity is possible. "	( Challenges for Detecting Valproic Acid in a Nontargeted Urine Drug Screening Method. Black, MJ; Drummer, OH; Pope, JD; Schneider, HG, 2017)	2.2
"Valproic acid (VPA) is a short-chain, fatty acid type histone deacetylase inhibitor (HDACi), which can cause growth arrest and induce differentiation of transformed cells. "	( Valproic Acid-Functionalized Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents. Cao, JJ; Ji, LN; Mao, ZW; Tan, CP; Ye, RR, 2017)	3.34
"Valproic acid (VPA) is a first-line antiepileptic drug, though its metabolism is affected by genetic polymorphisms and varies between individuals."	( Early post-traumatic seizures are associated with valproic acid plasma concentrations and UGT1A6/CYP2C9 genetic polymorphisms in patients with severe traumatic brain injury. Hu, J; Sun, Y; Wu, X; Yu, J; Yuan, Q, 2017)	1.43
"Valproic acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. "	( The pharmacogenomics of valproic acid. Chen, XP; Li, HL; Luo, J; Shi, LH; Zhang, ZL; Zhu, MM, 2017)	2.2
"Valproic Acid is a commonly used psychiatric drug primarily used as a mood stabilizer. "	( Sudden valproate-induced hyperammonemia managed with L-carnitine in a medically healthy bipolar patient: Essential review of the literature and case report. Ballabio, M; Cattaneo, CI; D'Innella, P; Fornaro, M; Ressico, F; Valsesia, R, 2017)	1.9
"Valproic acid overdose is a relatively rare and electrocardiographic changes usually consist of tachycardia and nonspecific changes, but ischemic changes may occur and usually transient and require only recognition."	( Valproic Acid Overdose Review of a Case With Electrocardiographic Changes. Muñiz, AE, 2017)	3.34
"Valproic acid (VPA) is an older first-line antiepileptic drug with a complex pharmacokinetic (PK) profile, currently under investigation for several novel neurologic and non-neurologic indications. "	( Physiologically based pharmacokinetic modeling of disposition and drug-drug interactions for valproic acid and divalproex. Alam, HB; Conner, TM; Georgoff, PE; Nikolian, VC; Pai, MP; Reed, RC; Sun, D; Zhang, T, 2018)	2.14
"Valproic acid (VPA) is a drug mainly used to treat epilepsy. "	( [Treatment of encephalopathy by means of valproic acid with carglumic acid: two case reports and a review of the literature]. Ceberio-Hualde, L; Cebrian-Novella, D; Diaz Alvarez-Mediavilla, J; Gomez-Del Olmo, V; Nava-Mateos, JJ; Roiz-Rey, P, 2017)	2.16
"Valproic acid (VPA) is a very potent anti-cancer and neuro-protective drug probably by its HDAC inhibiting properties, which may cause steatosis in the liver. "	( Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Claessen, SMH; de Kok, TMCM; Jennen, DGJ; Kleinjans, JCS; Theunissen, DHJ; van Breda, SGJ; van Herwijnen, M, 2018)	2.16
"Valproic acid (VPA) is a short-chain branched fatty acid with anti-epileptic, neuro-protective and anti-inflammatory effects."	( Valproic acid attenuates inflammation of optic nerve and apoptosis of retinal ganglion cells in a rat model of optic neuritis. Li, H; Liu, Q; Niu, X; Wang, Z; Yang, J; Zhao, C; Zhao, L, 2017)	2.62
"Valproic acid (VPA) is a well-established therapeutic used in treatment of seizure and mood disorders as well as migraines and a known hepatotoxicant. "	( Valproic acid disrupts the oscillatory expression of core circadian rhythm transcription factors. Griggs, CA; Jaime-Frias, R; Malm, SW; Smith, CL, 2018)	3.37
"Valproic acid (VPA) is a histone deacetylase inhibitor that improves outcomes in large animal models of trauma. "	( Valproic acid induces prosurvival transcriptomic changes in swine subjected to traumatic injury and hemorrhagic shock. Alam, HB; Athey, B; Chtraklin, K; Eidy, H; Georgoff, PE; Ghandour, MH; Higgins, G; Nikolian, VC; Williams, A, 2018)	3.37
"Valproic acid (VA) is an antiepileptic that is also used for the treatment of bipolar disorders. "	( Neuroprotective effects of valproic acid on brain ischemia are related to its HDAC and GSK3 inhibitions. Correia, AO; Costa, RO; da Silva Ribeiro, AE; de Barros Viana, GS; de Siqueira, KP; Dos Santos, GCA; Lima, DGS; Lucetti, DL; Lucetti, ECP; Moura, JA; Neves, KRT; Parente, LLT; Silva, MR, 2018)	2.22
"Valproic acid (VPA) is a commonly used drug for clinical treatment of seizure disorders."	( Valproic Acid Promotes Apoptosis and Cisplatin Sensitivity Through Downregulation of H19 Noncoding RNA in Ovarian A2780 Cells. Amini-Farsani, Z; Ghasemi-Dehkordi, P; Sajadpoor, Z; Sangtarash, MH; Shamsara, M; Teimori, H; Yadollahi, F, 2018)	2.64
"Valproic acid (VPA) is a widely used anti‑epileptic and anti‑convulsant drug."	( Valproic acid prevents glucocorticoid‑induced osteonecrosis of the femoral head of rats. Chen, YX; Feng, Y; Guo, SC; Tao, SC; Wei, ZY; Yin, JH; Zhang, CQ; Zhou, D, 2018)	2.64
"Valproic acid (VPA) is an anticonvulsive drug commonly used for epilepsy treatment and its use is associated to increased risk of neuropsychiatric disorders."	( Deformation of Mitochondrial Cristae in Human Neural Progenitor Cells Exposed to Valproic Acid. Costa, RMD; Karmirian, K; Rehen, SK, 2018)	1.43
"Valproic acid (VPA) is a first-line anti-epileptic drug that is used in the treatment of generalized and partial seizures. "	( Population pharmacokinetics of valproic acid in epileptic children: Effects of clinical and genetic factors. Chen, Y; Guo, Y; Wang, Z; Xu, S; Zhao, L; Zhao, M, 2018)	2.21
"Valproic acid (VPA) is an anticonvulsant and mood stabilizer that, when used during the gestational period, increases the risk of ASD in the offspring."	( Neuroimmune Alterations in Autism: A Translational Analysis Focusing on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid. Bambini-Junior, V; Deckmann, I; Fontes-Dutra, M; Gottfried, C; Schwingel, GB, 2018)	1.41
"Valproic acid (VPA) is an inhibitor of histone deacetylases (HDACs) that can regulate differentiation and proliferation of stem cells by epigenetic mechanisms. "	( Immunocytochemical analysis of valproic acid induced histone H3 and H4 acetylation during differentiation of rat adipose derived stem cells into neuron-like cells. Abdanipour, A; Hassoun, HK; Rezaei, F; Taheri, T; Tiraihi, T, 2018)	2.21
"Valproic acid (VPA) is a recently emerged antineoplastic histone deacetylase inhibitor."	( Synergistic antitumor activity of oridonin and valproic acid on HL-60 leukemia cells. Li, W; Ma, L, 2019)	1.49
"Valproic acid (VPA) is an anticonvulsant drug in both human and rodents with teratogenic effects during pregnancy."	( Benefits of Fenofibrate in prenatal valproic acid-induced autism spectrum disorder related phenotype in rats. Mirza, R; Sharma, B, 2019)	1.51
"Valproic acid (VPA) is a histone deacetylase (HDAC) inhibitor that has shown positive results on SMA both in experimental and cohort studies."	( Efficacy and Safety of Valproic Acid for Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis. Abo-Elghar, H; Doheim, MF; ELdoadoa, MF; Elshafay, A; Hieu, TH; Hirayama, K; Holloway, SK; Huy, NT; Kassem, MAM, 2019)	1.55
"Valproic acid (VPA) is a commonly used antiepileptic drug (AED). "	( Valproic acid and Stevens-Johnson syndrome: a systematic review of descriptive studies. Kashyap, A; Rashid, M; Undela, K, 2019)	3.4
"Valproic acid is an established structural and neurodevelopmental teratogen. "	( The effects of valproic acid on early pregnancy human placentas: Pilot ex vivo analysis in cultured placental villi. Eisenberg, I; Eyal, S; Imbar, T; Shmuel, M; Tetro, N; Wohl, D; Yagel, S, 2019)	2.31
"Valproic acid (VPA) is a clinical medicine primarily prescribed to control epileptic symptoms. "	( Potential biomarker of fibroblast growth factor 21 in valproic acid-treated livers. Chen, J; Guo, C; Li, R; Liang, X; Xu, X, 2019)	2.21
"Valproic acid (VPA) is an antiepileptic drug with narrow therapeutic window."	( A Chinese herb formula decreases the monocarboxylate transporter-mediated absorption of valproic acid in rats. Chao, PD; Hou, YC; Kao, LJ; Tsai, SY; Yu, CP, 2013)	1.33
"Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). "	( Valproic acid use during radiation therapy for glioblastoma associated with improved survival. Barker, CA; Beal, K; Bishop, AJ; Chan, TA; Chang, M, 2013)	3.28
"Valproic acid (VPA) is a blocker of histone deacetylase widely used to treat epilepsy, bipolar disorders, and migraine; its administration during pregnancy increases the risk of autism spectrum disorder (ASD) in the child. "	( Rearrangement of the dendritic morphology in limbic regions and altered exploratory behavior in a rat model of autism spectrum disorder. Atzori, M; Bringas, ME; Carvajal-Flores, FN; Flores, G; López-Ramírez, TA, 2013)	1.83
"Valproic acid (VA) is a major antiepileptic drug, used for several therapeutic indications. "	( Valproic acid: an anticonvulsant drug with potent antinociceptive and anti-inflammatory properties. Correia, AO; da Graça Naffah-Mazzacorati, M; de Castro Brito, GA; de Oliveira Gonçalves, D; Félix, FH; Leal, LK; Neves, KR; Santos Cerqueira, G; Siqueira, RM; Viana, GS; Ximenes, JC, 2013)	3.28
"Valproic acid is a drug used for the treatment of a variety of psychiatric and neurological disorders. "	( Valproic acid-induced parkinsonism: levodopa responsiveness with dyskinesia. Factor, SA; Silver, M, 2013)	3.28
"Valproic acid (VPA) is a histone deacetylase inhibitor that may decrease cellular metabolic needs following traumatic injury. "	( Beneficial effects of histone deacetylase inhibition with severe hemorrhage and ischemia-reperfusion injury. Alam, H; Causey, MW; Hempel, J; Hoffer, Z; Jin, G; Martin, M; Miller, S; Stallings, JD, 2013)	1.83
"Valproic acid (VPA) is a branched-chain saturated fatty acid with a long history of clinical use as an antiepileptic drug (AED). "	( A proapoptotic effect of valproic acid on progenitors of embryonic stem cell-derived glutamatergic neurons. Fujiki, R; Fujitani, M; Sato, A; Yamashita, T, 2013)	2.14
"Valproic acid is a widely-used first-generation antiepileptic drug, prescribed predominantly in epilepsy and psychiatric disorders. "	( Adverse drug reactions induced by valproic acid. Nanau, RM; Neuman, MG, 2013)	2.11
"Valproic acid is an anticonvulsant and a mood-stabilizing drug that has been used for decades."	( Valproic acid promotes human hair growth in in vitro culture model. Choi, SJ; Eun, HC; Jo, SJ; Kim, KH; Kwon, O; Lee, JY; Park, PJ; Park, WS; Yoon, SY, 2013)	2.55
"Valproic acid (VPA) is a widely used antiepileptic drug, which has recently been reported to affect ADSC differentiation in mice and rats; however, few studies have been performed on dogs."	( Valproic acid, a histone deacetylase inhibitor, decreases proliferation of and induces specific neurogenic differentiation of canine adipose tissue-derived stem cells. Aoki, T; Fujii, Y; Hisasue, M; Kurihara, Y; Miyazaki, Y; Murayama, O; Onuki, A; Saito, M; Sakaue, M; Suzuki, T; Takizawa, T; Tanaka, K, 2014)	2.57
"Valproic acid (VPA) is a widely prescribed anticonvulsant for the treatment of epilepsy. "	( Valproic acid is a novel activator of AMP-activated protein kinase and decreases liver mass, hepatic fat accumulation, and serum glucose in obese mice. Avery, LB; Bumpus, NN, 2014)	3.29
"Valproic acid is an anticonvulsant and mood-stabilizing drug used to treat epilepsy, bipolar disorder and migraines."	( Developmental exposure to valproic acid alters the expression of microRNAs involved in neurodevelopment in zebrafish. Aluru, N; Deak, KL; Hahn, ME; Jenny, MJ, )	1.15
"Valproic acid (VPA) is an effective antiepileptic drug that may induce progressive microvesicular steatosis. "	( Valproyl-CoA inhibits the activity of ATP- and GTP-dependent succinate:CoA ligases. de Almeida, IT; Duran, M; IJlst, L; Luís, PB; Ruiter, J; Silva, MF; Wanders, RJ, 2014)	1.85
"Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar disorders. "	( Valproic acid causes proteasomal degradation of DICER and influences miRNA expression. Andres, DA; Convertini, P; de la Grange, P; Lemoine, F; Shen, M; Stamm, S; Xu, X; Zhang, Z, 2013)	3.28
"Valproic acid (VPA) is a broad-spectrum inhibitor of class I and II histone deacetylases and shows great anticancer activity in a variety of human cancers."	( VPA inhibits renal cancer cell migration by targeting HDAC2 and down-regulating HIF-1α. Che, J; Li, W; Li, X; Liu, M; Wang, GC; Yang, FP; Yang, FQ; Zhai, W; Zheng, JH, 2014)	1.12
"Valproic acid (VPA) is an anticonvulsant that is a known risk factor for autism in prenatally exposed children."	( Degraded auditory processing in a rat model of autism limits the speech representation in non-primary auditory cortex. Borland, MS; Carraway, RS; Centanni, TM; Engineer, CT; Im, KW; Kilgard, MP; Moreno, NA; Wilson, LG, 2014)	1.12
"Valproic acid (VPA) is a widely used antiepileptic drug and also prescribed to treat migraine, chronic headache and bipolar disorder. "	( Valproic acid triggers increased mitochondrial biogenesis in POLG-deficient fibroblasts. Chinnery, PF; Elliott, HR; Horvath, R; Karaman, BS; Relton, C; Sitarz, KS, 2014)	3.29
"Valproic acid (VA) is a drug widely used to treat epilepsy and bipolar disorder, at recommended serum concentrations ranging form 50 to 100μg ml(-1). "	( Simple procedure for determination of valproic acid in dried blood spots by gas chromatography-mass spectrometry. Álvares da Silva, C; Antunes, MV; Hidalgo, P; Linden, R; Rhoden, L, 2014)	2.12
"Valproic acid (VPA) is an inhibitor of PE and could possibly have an effect on the severity of chronic inflammation."	( Targeting prolyl endopeptidase with valproic acid as a potential modulator of neutrophilic inflammation. Abdul Roda, M; Blalock, JE; Braber, S; Folkerts, G; Gaggar, A; Hardison, MT; Jablonsky, MJ; Jackson, PL; Redegeld, FA; Sadik, M, 2014)	1.4
"Valproic acid (VPA) is an anti-epileptic drug that also acts as a class I histone deacetylase inhibitor."	( Dasatinib accelerates valproic acid-induced acute myeloid leukemia cell death by regulation of differentiation capacity. Heo, SK; Jo, JC; Kim, H; Noh, EK; Park, JH; Yoon, DJ, 2014)	1.44
"Valproic acid (VPA) acts as a specific inhibitor of class I HDACs and it use has been proven to be safe since a long time."	( Valproic acid enhances the anti-tumor effect of pegylated interferon-α towards pancreatic cancer cell lines. Ikemoto, T; Imura, S; Iwahashi, S; Morine, Y; Shimada, M; Sugimoto, K; Utsunomiya, T, 2014)	3.29
"Valproic acid is an anti-convulscant drug that is widely used in the treatment of different types of epilepsy and since its introduction the clinical use has increased rapidly both as a sole agent and in combination therapies. "	( A physiologically based pharmacokinetic model for Valproic acid in adults and children. Aarons, L; Ogungbenro, K, 2014)	2.1
"Valproic acid is an inhibitor of class I histone deacetylases. "	( Could valproic acid be an effective anticancer agent? The evidence so far. Brandes, JC; Brodie, SA, 2014)	2.33
"Valproic acid (VPA) is a commonly prescribed drug for those affected by epilepsy and bipolar disorders. "	( Brief report novel mechanism for valproate-induced teratogenicity. Fathe, K; Finnell, RH; Palacios, A, 2014)	1.85
"Valproic acid (VPA) is a known teratogenic drug. "	( Middle and inner ear malformations in two siblings exposed to valproic acid during pregnancy: a case report. Casselman, J; De Kegel, A; Dhooge, I; Janssens, S; Maes, L; Van Houtte, E, 2014)	2.09
"Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. "	( Biological screening of novel derivatives of valproic acid for anticancer and antiangiogenic properties. Baabbad, A; El-Faham, A; Elkayal, AM; Farooq, M; Hamed, EA; Ibrahim, MF; Khattab, SN; Taha, NA; Wadaan, MA, 2014)	2.1
"Valproic acid is an effective first line drug for the treatment of epilepsy. "	( Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase. Choonara, I; Edwards, IR; Star, K, 2014)	3.29
"Valproic acid (VPA) is a drug used for the treatment of epilepsy, bipolar psychiatric disorders, and migraine. "	( Edaravone ameliorates the adverse effects of valproic acid toxicity in small intestine. Alev, B; Emekli-Alturfan, E; Koc-Ozturk, L; Oktay, S; Tunali, S; Tunali-Akbay, T; Yanardag, R; Yarat, A, 2015)	2.12
"Valproic acid (VPA) is an anti-epileptic drug with HDACi and anticancer activity."	( Phase 1/2 study of valproic acid and short-course radiotherapy plus capecitabine as preoperative treatment in low-moderate risk rectal cancer-V-shoRT-R3 (Valproic acid--short Radiotherapy--rectum 3rd trial). Aloj, L; Avallone, A; Bianco, F; Botti, G; Budillon, A; Caracò, C; Cavalcanti, E; D'Angelo, V; Daniele, G; Delrio, P; Di Gennaro, E; Di Maio, M; Gallo, C; Granata, C; Iaffaioli, VR; Lastoria, S; Maiolino, P; Marone, P; Maurea, N; Montano, M; Muto, P; Pecori, B; Perrone, F; Petrillo, A; Piccirillo, MC; Roca, MS; Romano, G; Silvestro, L; Tatangelo, F; Terranova Barberio, M, 2014)	1.45
"Valproic acid (VA) is a branch chain fatty acid that is widely used to treat epilepsy and convulsion. "	( Derivatization oriented strategy for enhanced detection of valproic acid and its metabolites in human plasma and detection of valproic acid induced reactive oxygen species associated protein modifications by mass spectrometry. Lu, CY; Wu, CY, 2014)	2.09
"Valproic acid (VPA) is a first-line drug used for the treatment of epilepsy and migraine as well as established as a HDAC inhibitor."	( Sodium valproate ameliorates diabetes-induced fibrosis and renal damage by the inhibition of histone deacetylases in diabetic rat. Jena, G; Khan, S; Tikoo, K, 2015)	1.14
"Valproic acid is an anticonvulsant that also inhibits histone deacetylase (HDAC), a property that could worsen pulmonary function in patients with chronic obstructive pulmonary disease (COPD). "	( Safety of valproic acid in patients with chronic obstructive pulmonary disease: a population-based cohort study. Antoniou, T; Camacho, X; Gomes, T; Juurlink, DN; Mamdani, MM; Yao, Z, 2015)	2.26
"Valproic acid is an effective anti-epileptic drug; however, when taken by pregnant women to treat epilepsy, it can produce cardiac developmental defects in fetuses."	( The Phosphorylation State of GSK3β Serine 9 Correlated to the Development of Valproic Acid-Associated Fetal Cardiac Teratogenicity, Fetal VPA Syndrome, Rescued by Folic Acid Administration. Chu, SL; Ho, YL; Huang, PT; Liou, HH; Tsai, HJ; Yu, WH, 2016)	1.38
"Valproic acid (VPA) is a widely prescribed drug for seizures and bipolar disorder in clinic."	( Wnt signaling pathway participates in valproic acid-induced neuronal differentiation of neural stem cells. Li, S; Liu, Y; Long, ZY; Wang, L; Wu, YM, 2015)	1.41
"Valproic acid (VPA) is an antiepileptic drug that has been associated with impaired hemostasis and increased risk for postsurgical bleeding. "	( Effects of chronic administration of valproic acid to epileptic patients on coagulation tests and primary hemostasis. Canevini, MP; Cattaneo, M; Chiesa, V; Fontana, G; Lussana, F; Vignoli, A; Zighetti, ML, 2015)	2.13
"Valproic acid (VA) is a widely used antiepileptic drug. "	( [Therapeutic Drug Monitoring of Valproic Acid in Children: A Prospective Study of The Effect of The Compliance and The Economic Level on the Trough Plasmatic Concentrations and Epileptic Seizures]. Charfi, R; Klouz, A; Lakhal, M; Salouage, I; Trabelsi, S, )	1.86
"Valproic acid (VPA) is a well-known drug used to treat seizure disorders and epilepsy, and has been shown to inhibit HDACs."	( Inhibitory effects of valproic acid in DNA double-strand break repair after irradiation in esophageal squamous carcinoma cells. Fushida, S; Harada, S; Hayashi, H; Kinoshita, J; Makino, I; Makita, N; Miyashita, T; Nakagawara, H; Nakanuma, S; Ninomiya, I; Ohta, T; Okamoto, K; Oyama, K; Sakai, S; Tajima, H; Takamura, H; Tsukada, T, 2015)	1.45
"Valproic acid (VPA) is a widely used antiepileptic drug and first-line treatment in bipolar disorder, although the mechanisms underlying its therapeutic effects are largely unknown. "	( Valproic acid exposure leads to upregulation and increased promoter histone acetylation of sepiapterin reductase in a serotonergic cell line. Balasubramanian, D; Deng, AX; Doudney, K; Hampton, MB; Kennedy, MA, 2015)	3.3
"Valproic acid (VPA) is a histone deacetylase inhibitor, and lithium (Li) may have downstream epigenetic actions."	( Search for common targets of lithium and valproic acid identifies novel epigenetic effects of lithium on the rat leptin receptor gene. Ewald, ER; Gould, TD; Guintivano, J; Lee, RS; Ly, M; Moran, TH; Pirooznia, M; Potash, JB; Tamashiro, KL, 2015)	1.4
"Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models. "	( A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma. Camphausen, K; Chang, MG; Fine, HA; Holdford, DJ; Krauze, AV; Myrehaug, SD; Shih, J; Smith, S; Tofilon, PJ, 2015)	2.08
"Valproic acid (VPA) is a useful antiepileptic drug for controlling different types of epilepsy. "	( [The prevalence of obesity and metabolic syndrome in paediatric patients with epilepsy treated in monotherapy with valproic acid]. Carmona-Vazquez, CR; Diaz-Garcia, L; Greenawalt, SR; Pena-Landin, DM; Ruiz-Garcia, M, 2015)	2.07
"Valproic acid (VPA) is a widely used antiepileptic drug, which has recently been reported to modulate the neuronal differentiation of adipose tissue-derived stem cells (ASCs) in humans and dogs. "	( Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid, a histone deacetylase inhibitor. Fujita, Y; Hayashi, D; Lynch, J; Miyazaki, Y; Murayama, O; Okubo, T; Sakaue, M; Suzuki, T; Takizawa, T; Tanaka, K; Tsukamoto, A; Yaguchi, T, 2016)	2.1
"Valproic acid (VPA) is an anticonvulsant drug used for the treatment of epilepsy and bipolar disorder. "	( Ultrasound-assisted dispersive liquid-liquid microextraction followed by GC-MS/MS analysis for the determination of valproic acid in urine samples. Chauhan, A; Gupta, MK; Jain, R; Pandey, V; Reddy Mudiam, MK, 2015)	2.07
"Valproic acid (VPA) is a neurotherapeutic drug prescribed for seizures, bipolar disorder, and migraine, including women of reproductive age. "	( Valproic acid stimulates proliferation of glial precursors during cortical gliogenesis in developing rat. DiCicco-Bloom, E; Dreyfus, C; Lee, HJ, 2016)	3.32
"Valproic acid (VPA) is an anti-convulsant drug that is recently shown to have neuroregenerative therapeutic actions. "	( Valproic acid mediates miR-124 to down-regulate a novel protein target, GNAI1. Goh, WW; Lim, VK; Oikawa, H; Sng, JC; Wong, L, 2015)	3.3
"Valproic acid (VPA) is a broad-spectrum antiepileptic drug (AED) that is also used for migraine prophylaxis, but its clinical use is limited by its side effect profile."	( sec-Butylpropylacetamide (SPD) has antimigraine properties. Bates, EA; Bialer, M; Brennan, KC; Kaufmann, D; Saunders, GH; White, HS; Wilcox, K; Yagen, B, 2016)	1.16
"Valproic acid (VPA) is a potential alternative or adjunct treatment."	( Valproic Acid for Treatment of Hyperactive or Mixed Delirium: Rationale and Literature Review. Ament, A; Lolak, S; Maldonado, JR; Miller Cramer, AC; Sher, Y, )	2.3
"Valproic acid is a versatile antiepileptic drug that is often used in the acute care setting. "	( Pharmacokinetics and Clinical Utility of Valproic Acid Administered via Continuous Infusion. Albuja, AC; Baumann, RJ; Bensalem-Owen, M; Cook, AM; Kapoor, S; Mathias, S; Stewart, AM; Zafar, MS, 2016)	2.14
"Valproic acid (VPA) is an anti-epileptic drug used in patients with convulsive seizures and psychic disorders. "	( High-calorie diet inflates steatogenic effects of valproic acid in mice. Anuradha, CV; Bhavani, K; Sathiya Priya, C, 2016)	2.13
"Valproic acid (VPA) is a short-chain fatty acid, widely used for the treatment of seizures and bipolar mood disorder."	( Protective effect of valproic acid on cultured motor neurons under glutamate excitotoxic conditions. Ultrastructural study. Matyja, E; Nagańska, E; Rafałowska, J; Taraszewska, A, 2015)	1.46
"Valproic acid (VPA) is a small fatty acid used for treatment of different neurologic diseases such as epilepsy, migraines or bipolar disorders. "	( Inhibition of herpes virus infection in oligodendrocyte cultured cells by valproic acid. Bello-Morales, R; Crespillo, AJ; Lerma, L; López-Guerrero, JA; Martín-Acebes, MA; Praena, B; Sobrino, F; Tabarés, E; Vázquez-Calvo, A, 2016)	2.11
"Valproic acid (VPA) is an anti-epileptic drug with properties of a histone deacetylase inhibitor (HDACi). "	( Valproic acid, compared to other antiepileptic drugs, is associated with improved overall and progression-free survival in glioblastoma but worse outcome in grade II/III gliomas treated with temozolomide. Dietrich, J; Le, A; McDonnell, E; Nahed, BV; Redjal, N; Reinshagen, C; Walcott, BP, 2016)	3.32
"Valproic acid (VPA) is a widely prescribed anticonvulsant drug."	( Improvement of oral contraceptive-induced glucose dysregulation and dyslipidemia by valproic acid is independent of circulating corticosterone. Kim, I; Olatunji, LA; Omolekulo, TE; Usman, TO, 2016)	1.38
"Valproic acid (VPA) is a pan-HDAC inhibitor used clinically to treat bipolar and seizure disorders."	( Safety and efficacy of valproic acid treatment in SCA3/MJD patients. Chuang, DM; Jiang, H; Lei, LF; Song, WH; Tang, BS; Wang, JL; Yang, GP, 2016)	1.47
"Valproic acid (VPA) is a broad spectrum antiepileptic drug (AED) that is generally regarded as a first-choice agent for most forms of idiopathic and symptomatic generalised epilepsies. "	( Valproic Acid Metabolism and its Consequences on Sexual Functions. Belcastro, V; Castagnino, M; Cofini, M; Leo, A; Mencaroni, E; Russo, E; Verrotti, A, 2016)	3.32
"Valproic acid (VPA) is a multi-target drug and an inhibitor of histone deacetylase (HDAC). "	( Prenatal Exposure to Histone Deacetylase Inhibitors Affects Gene Expression of Autism-Related Molecules and Delays Neuronal Maturation. Ago, Y; Hasebe, S; Hashimoto, H; Inoue, A; Kawanai, T; Matsuda, T; Onaka, Y; Takuma, K; Taruta, A; Watanabe, R, 2016)	1.88
"Valproic acid (VA) is a histone deacetylase (HDAC) inhibitor that has antiproliferative effects on several types of cancer, including thyroid cancer. "	( A phase II trial of valproic acid in patients with advanced, radioiodine-resistant thyroid cancers of follicular cell origin. Kebebew, E; Merkel, R; Neychev, V; Nilubol, N; Patel, D; Reynolds, JC; Sadowski, SM; Yang, L, 2017)	2.22
"Valproic acid is a first-line anti-epileptic drug and a proven HDAC inhibitor."	( Anti-fibrotic effects of valproic acid: role of HDAC inhibition and associated mechanisms. Ahirwar, K; Jena, G; Khan, S, 2016)	1.46
"Valproic acid (VPA) is a broad-spectrum antiepileptic drug used for a variety of neurologic disorders. "	( Steady-state pharmacokinetic simulation of intermittent vs. continuous infusion valproic acid therapy in non-critically ill and critically ill patients. Cook, AM; Van Matre, ET, 2016)	2.1
"Valproic acid (VPA) is an anti-epileptic drug with teratogenicity activity that has been related to autism. "	( Prenatal exposure to sodium valproate alters androgen receptor expression in the developing cerebellum in a region and age specific manner in male and female rats. Brug, B; Hernandez, ME; Manzo, J; Miquel, M; Perez-Pouchoulen, M; Saft, P; Toledo, R, 2016)	1.88
"Valproic acid (VPA) is a drug widely use for the treatment of epilepsy in both children and adults. "	( Resveratrol prevents oxidative damage and loss of sperm motility induced by long-term treatment with valproic acid in Wistar rats. Baldisserotto, B; Barreto, KP; Finamor, IA; Glanzner, WG; Gonçalves, PB; Ourique, GM; Pavanato, MA; Pês, TS; Saccol, EM, 2016)	2.09
"Valproic acid (VPA) is an effective treatment in juvenile myoclonic epilepsy (JME), but concerns on its use during pregnancy are remarkable. "	( Levetiracetam and Valproate Retention Rate in Juvenile Myoclonic Epilepsy. González-Cuevas, M; Quintana, M; Raspall-Chaure, M; Sala-Padró, J; Salas-Puig, X; Santamarina, E; Sueiras-Gil, M; Toledo, M, )	1.57
"Valproic acid (VPA) is a HDAC inhibitor that has antitumor activity at mM range."	( N-(2-hydroxyphenyl)-2-propylpentanamide, a valproic acid aryl derivative designed in silico with improved anti-proliferative activity in HeLa, rhabdomyosarcoma and breast cancer cells. Bermúdez-Lugo, JA; Chávez-Blanco, A; Correa-Basurto, AM; Correa-Basurto, J; Dueñas-González, A; Fragoso-Vázquez, MJ; García-Sánchez, JR; Méndez-Luna, D; Mendieta-Wejebe, JE; Padilla-Martínez, II; Pérez-González, OA; Prestegui-Martel, B; Trujillo-Ferrara, J, 2016)	1.42
"Valproic acid (VPA) is a histone deacetylase inhibitor that apart from its anticonvulsive effects in some retrospective studies has been suggested to lead to a superior outcome of glioblastoma patients."	( Molecular dissection of the valproic acid effects on glioma cells. Hau, P; Herold-Mende, C; Hoja, S; Proescholdt, M; Rehli, M; Riemenschneider, MJ; Schulze, M, 2016)	1.45
"Valproic acid (VPA) is a drug recently has been appreciated for its neuroprotective and neurotrophic properties in various SCI models."	( Valproic acid preserves motoneurons following contusion in organotypic spinal cord slice culture. Dargahi, L; Nabiuni, M; Pandamooz, S; Salehi, MS, 2017)	2.62
"Valproic acid (VPA), which is an anti-epileptic and anti-depressive drug, is one of the teratogens to cause ASD onset."	( Downregulation of glutamatergic and GABAergic proteins in valproric acid associated social impairment during adolescence in mice. Chan, CW; Chau, DK; Choi, AY; Leung, WN; Yang, W, 2017)	1.18
"Valproic acid (VPA) is a well-known antiepileptic drug that exhibits antitumor activities through its action as a histone deacetylase inhibitor. "	( Valproic Acid Increases CD133 Positive Cells that Show Low Sensitivity to Cytostatics in Neuroblastoma. Doktorová, H; Eckschlager, T; Groh, T; Hraběta, J; Khalil, MA; Procházka, P, 2016)	3.32
"Valproic acid (VA) is a pharmacologically important histone deacetylase inhibitor that recently garnered attention as an anticancer agent. "	( Combined Transcriptomics and Chemical-Genetics Reveal Molecular Mode of Action of Valproic acid, an Anticancer Molecule using Budding Yeast Model. Golla, U; Joseph, D; Tomar, RS, 2016)	2.1
"Valproic acid is a mood-stabilizing anticonvulsant. "	( Valproic Acid and Hepatic Steatosis: A Possible Link? About a Case Report. Masmoudi, J; Mnif, L; Sellami, R, 2016)	3.32
"Valproic acid (VPA) is a widely used antiepileptic drug with acceptable safety and efficacy in treating pediatric patients with various kinds of seizures. "	( Effects of UGT1A6 and GABRA1 on Standardized Valproic Acid Plasma Concentrations and Treatment Effect in Children With Epilepsy in China. Fang, F; Feng, W; Gao, B; Mei, S; Wu, X; Yang, W; Yu, Y; Zhao, Z; Zhu, L, 2016)	2.14
"Valproic acid (VPA) is a medication used to treat multiple neuroscience conditions. "	( Valproic Acid: Special Considerations and Targeted Monitoring. Collins-Yoder, A; Lowell, J, 2017)	3.34
"Valproic acid (VPA) is an antiepileptic drug, which its usage is limited due to its hepatotoxicity. "	( Zinc Deficiency and Oxidative Stress Involved in Valproic Acid Induced Hepatotoxicity: Protection by Zinc and Selenium Supplementation. Ahangar, N; Ghasemi, M; Naderi, M; Noroozi, A; Shaki, F; Zamani, E, 2017)	2.15
"Valproic acid (VPA) is an FDA-approved medication widely prescribed for seizures, migraines, and mixed or manic episodes in bipolar disorder. "	( Reversible Encephalopathy due to Valproic Acid Induced Hyperammonemia in a Patient with Bipolar I Disorder: A Cautionary Report. Birur, B; Fargason, RE; Landry, KB; Patel, N, 2017)	2.18
"Valproic acid (VPA) is a first-line antiepileptic drug. "	( Population pharmacokinetic modelling of valproic acid and its selected metabolites in acute VPA poisoning. Jawień, W; Kłys, M; Piekoszewski, W; Wilimowska, J, 2017)	2.17
"Valproic acid (VPA) is a widely used antiepileptic drug (AED). "	( Drug interaction between valproic acid and carbapenems in patients with epileptic seizures. Chen, NC; Chen, SD; Chuang, YC; Hsiao, SC; Huang, CR; Lin, CH; Lu, YT; Tsai, WC, 2017)	2.2
"Valproic acid (VPA) is a major antiepileptic drug (AED) with efficacy against multiple seizure types. "	( Increase in antiepileptic efficacy during prolonged treatment with valproic acid: role of inhibition of histone deacetylases? Czapp, M; Hoffmann, K; Löscher, W, 2008)	2.02
"Valproic acid (VPA) is a widely used and well-tolerable antiepileptic drug in epileptic patients. "	( The effects of biotin supplementation on serum and liver tissue biotinidase enzyme activity and alopecia in rats which were administrated to valproic acid. Akin, R; Arslan, M; Balamtekin, N; Kurt, I; Ozcan, O; Unay, B; Vurucu, S, 2009)	2
"Valproic acid is a histone deacetylase inhibitor."	( Phase I study of epigenetic modulation with 5-azacytidine and valproic acid in patients with advanced cancers. Alexander, S; Braiteh, F; Garcia-Manero, G; Hong, D; Johnson, MM; Kurzrock, R; Silva, Lde P; Soriano, AO; Wolff, J; Yang, H, 2008)	1.31
"Valproic acid (VPA) is a widely used anticonvulsant that is also approved for mood disorders, bipolar depression, and migraine. "	( Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Argikar, UA; Remmel, RP, 2009)	2.07
"Valproic acid (VPA) is a short-chain branched fatty with anti-inflammatory, neuro-protective and axon-remodeling effects. "	( Valproic acid attenuates inflammation in experimental autoimmune neuritis. Fauser, U; Schluesener, HJ; Zhang, Z; Zhang, ZY, 2008)	3.23
"Valproic acid (VPA) is a well-tolerated anticonvulsant that exerts anti-tumour activity as a histone deacetylase inhibitor. "	( In vivo anti-myeloma activity and modulation of gene expression profile induced by valproic acid, a histone deacetylase inhibitor. Amodio, N; Anderson, KC; Arbitrio, M; Bulotta, A; Calimeri, T; Caraglia, M; Di Martino, MT; Eramo, PO; Munshi, NC; Neri, P; Rossi, M; Tagliaferri, P; Tassone, P; Ventura, M; Viscomi, C, 2008)	2.01
"Valproic acid (VPA) is a histone deacetylase inhibitor previously shown to promote the proliferation and self-renewal of CD34(+) hematopoietic cells. "	( Valproic acid enhances the engraftability of human umbilical cord blood hematopoietic stem cells expanded under serum-free conditions. Chan, SL; Kraus, M; Lai, YS; Laning, J; Merchav, S; Seet, LF; Teng, E; Wnendt, S, 2009)	3.24
"Valproic acid (VPA) is a HDAC inhibitor used for the treatment of epilepsy."	( Valproic acid enhances bosutinib cytotoxicity in colon cancer cells. Boschelli, F; Cleris, L; Formelli, F; Gambacorti-Passerini, C; Magistroni, V; Mologni, L; Piazza, R, 2009)	2.52
"Valproic acid (VPA) is an HDACi and has been known as anti-epileptic agent for many years."	( Valproic acid and all-trans retinoic acid: meta-analysis of a palliative treatment regimen in AML and MDS patients. Bellos, F; Mahlknecht, U, 2008)	2.51
"Valproic acid (VPA) is a broad-spectrum antiepileptic drug that is now used commonly for several other neurological and psychiatric indications. "	( Carnitine in the treatment of valproic acid-induced toxicity. Hantson, P; Lheureux, PE, 2009)	2.08
"Valproic acid is a clinically relevant HDAC inhibitor, and PBMCs may serve as a surrogate for tumor histone acetylation in solid tumor malignancies. "	( Clinical and biological effects of valproic acid as a histone deacetylase inhibitor on tumor and surrogate tissues: phase I/II trial of valproic acid and epirubicin/FEC. Bicaku, E; Centeno, B; Daud, A; Kim, J; Lacevic, M; Marchion, D; Minton, S; Munster, P; Neuger, A; Sullivan, D, 2009)	2.07
"Valproic acid (VPA) is a known human teratogen. "	( Valproic acid in pregnancy: how much are we endangering the embryo and fetus? Ornoy, A, 2009)	3.24
"Valproic acid (VPA) is an antiepileptic drug that is now used for a variety of neurological and psychiatric indications. "	( Extracorporeal elimination in acute valproic acid poisoning. Thanacoody, RH, 2009)	2.07
"Valproic acid (VPA) is an established drug in the long-term therapy of epilepsy. "	( Epigenetic modifiers as anticancer drugs: effectiveness of valproic acid in neural crest-derived tumor cells. Ferreri, AM; Guerra, F; Orlandi, M; Papi, A; Rocchi, P, 2010)	2.05
"Valproic acid (VPA) is a frequently used antiepileptic agent and known teratogen. "	( Characterization of valproic acid-initiated homologous recombination. Sha, K; Winn, LM, 2010)	2.13
"Valproic acid (VPA) is a small molecule that inhibits histone deacetylase activity. "	( Valproic acid enhances recombinant mRNA and protein levels in transiently transfected Chinese hamster ovary cells. Baldi, L; Hacker, DL; Wulhfard, S; Wurm, F, 2010)	3.25
"Valproic acid (VPA) is a broad-spectrum inhibitor of histone deacetylase, which has been used in cancer therapy. "	( Curcumin p38-dependently enhances the anticancer activity of valproic acid in human leukemia cells. Chen, J; Kang, J; Wang, G; Wang, J; Wang, L, 2010)	2.04
"Valproic acid (VPA ) is a well-known antiepileptic drug with a significant teratogenic effect when administered during pregnancy. "	( Valproic acid transfer across human placental cotyledon during dual perfusion in vitro. Czuczwar, S; Kwasniewska, A; Semczuk, A; Semczuk, M; Semczuk-Sikora, A, 2010)	3.25
"Valproic acid is an anticonvulsant drug available in France since 1967. "	( [Therapeutic drug monitoring of valproate]. Bentué-Ferrer, D; Tribut, O; Verdier, MC, )	1.57
"Valproic acid (VPA) is a drug known for idiosyncratic hepatotoxicity and is associated with oxidative stress. "	( Role of oxidative metabolism in the effect of valproic acid on markers of cell viability, necrosis, and oxidative stress in sandwich-cultured rat hepatocytes. Abbott, FS; Chang, TK; Karagiozov, S; Kiang, TK; Surendradoss, J; Teng, XW, 2010)	2.06
"Valproic Acid (VPA) is a histone deacetylase inhibitor that holds promise for cancer therapy. "	( Does valproic acid induce neuroendocrine differentiation in prostate cancer? Carducci, M; Chowdhury, WH; Lupold, SE; Netto, G; Rodriguez, R; Shabbeer, S; Sidana, A; Toubaji, A; Wang, M, 2011)	2.33
"Valproic acid (VPA) is a short-chain fatty acid commonly used for treatment of neurological disorders. "	( Inhibition of enveloped virus infection of cultured cells by valproic acid. Martín-Acebes, MA; Saiz, JC; Sobrino, F; Vázquez-Calvo, A, 2011)	2.05
"Valproic acid (VPA) is a wide spread anticonvulsant and mood-stabilizing agent, the use of which is associated with hepatotoxicity, bone marrow suppression and osteomalacia. "	( Valproic acid augments vitamin D receptor-mediated induction of CYP24 by vitamin D3: a possible cause of valproic acid-induced osteomalacia? Bachleda, P; Bitman, M; Doricakova, A; Dvorak, Z; Novotna, A; Pavek, P; Vrzal, R, 2011)	3.25
"Valproic acid (VPA) is a teratogenic drug used in pregnant women for the treatment of epilepsy and mood disorders. "	( Severe fetal valproate syndrome: combination of complex cardiac defect, multicystic dysplastic kidney, and trigonocephaly. Cetinkaya, M; Köksal, N; Ozkan, H; Yapici, S, 2011)	1.81
"Valproic acid (VPA) is a well-tolerated and effective agent for the treatment of epilepsy, bipolar disorder, and schizoaffective disorder. "	( The real mechanism of VPA-induced hyperammonemia remains unknown. Huang, CC; Hung, CC; Li, TM; Wei, IH, )	1.57
"Valproic acid (VPA) is a known teratogen. "	( The teratogenic potencies of valproic acid derivatives and their effects on biological end-points are related to changes in histone deacetylase and Erk1/2 activities. Berezin, V; Bock, E; Ellerbeck, U; Gotfryd, K; Hansen, M; Kawa, A; Nau, H; Walmod, PS, 2011)	2.1
"Valproic acid (VLP) is a widely used anticonvulsant and mood-stabilizing drug that relieves the endoplasmic reticulum (ER) stress response, a pathogenetic process related to diabetes. "	( Wfs1 mutation makes mice sensitive to insulin-like effect of acute valproic acid and resistant to streptozocin. Ehrlich, K; Hansen, M; Kõks, S; Matto, V; Must, A; Oflijan, J; Punapart, M; Soomets, U; Terasmaa, A; Vasar, E, 2011)	2.05
"Valproic acid (VPA) is a first-line antiepileptic drug for therapy of patients with IGE."	( Valproate reduces spontaneous generalized spikes and waves but not photoparoxysmal reactions in patients with idiopathic generalized epilepsies. Boor, R; Ettle, E; Muhle, H; Siniatchkin, M; Stephani, U, 2011)	1.09
"Valproic acid (VPA) is an anticonvulsivant drug widely prescribed in the treatment of many forms of generalized epilepsy. "	( [Relationship between plasma concentrations of valproic acid and hepatotoxicity in patients receiving high doses]. Atheymen, R; Ben Mahmoud, L; Ghozzi, H; Hakim, A; Hammami, S; Sahnoun, Z; Zeghal, K, )	1.83
"Valproic acid (VPA) is a histone deacetylase inhibitor that can increase SMN levels in some SMA cells or SMA patients through activation of SMN2 transcription or splicing correction of SMN2 exon 7."	( Valproic acid increases SMN2 expression and modulates SF2/ASF and hnRNPA1 expression in SMA fibroblast cell lines. Harahap, IS; Lee, MJ; Matsuo, M; Morikawa, S; Nishimura, N; Nishio, H; Nurputra, DK; Saito, T; San, LP; Sasaki, N; Takeshima, Y; Yamamoto, T; Yusoff, S, 2012)	2.54
"Valproic acid (VPA) is an anticonvulsant and mood-stabilizing drug for the long-term treatment. "	( Valproic Acid related metabolic syndrome in patients with epilepsy. Kasradze, S; Mania, M; Okujava, N, 2011)	3.25
"Valproic acid is a commonly prescribed antiepileptic agent that causes birth defects including neural tube defects. "	( Valproic acid-induced DNA damage increases embryonic p27(KIP1) and caspase-3 expression: a mechanism for valproic-acid induced neural tube defects. Tung, EW; Winn, LM, 2011)	3.25
"Valproic acid (VPA) is a simple branched medium-chain fatty acid with expanding therapeutic applications beyond its prime anticonvulsant properties."	( Valproic acid utilizes the isoleucine breakdown pathway for its complete β-oxidation. de Almeida, IT; Diogo, L; Duran, M; Garcia, P; Ijlst, L; Luís, PB; Moedas, M; Ofman, R; Ruiter, JP; Silva, MF; Wanders, RJ, 2011)	3.25
"Valproic acid (VPA) is a broad-spectrum inhibitor of class I and II histone deacetylases and shows great anticancer activity in a variety of human cancers including breast cancer."	( VPA inhibits breast cancer cell migration by specifically targeting HDAC2 and down-regulating Survivin. Kang, J; Leng, Y; Song, C; Wang, G; Wang, L; Wang, X; Zhang, L, 2012)	1.1
"Valproic acid (VPA) is an HDAC inhibitor that has been evaluated in clinical studies."	( Exploration of the valproic acid binding site on histone deacetylase 8 using docking and molecular dynamic simulations. Bermúdez-Lugo, JA; Correa-Basurto, J; Ilizaliturri-Flores, I; Perez-Gonzalez, O; Rosales-Hernández, MC; Trujillo-Ferrara, J, 2012)	1.43
"Valproic acid is a safe, affordable histone deacetylase inhibitor."	( Potentiation of mitomycin C tumoricidal activity for transitional cell carcinoma by histone deacetylase inhibitors in vitro. Deb, AA; Koul, HK; Koul, S; Kumar, B; Lim, DD; Meacham, RB; Rove, KO; Wilson, SS, 2011)	1.09
"Valproic acid (VPA) is a well-established anticonvulsant drug that has been increasingly used in the treatment of many forms of generalized epilepsy. "	( Simultaneous determination of valproic acid and 2-propyl-4-pentenoic acid for the prediction of clinical adverse effects in Chinese patients with epilepsy. Chen, SD; Chen, ZJ; Fang, ZY; Huang, M; Li, JL; Shu, WY; Wang, HS; Wang, XD; Zhang, Y; Zhou, JQ; Zhou, LM, 2012)	2.11
"Valproic acid (VPA) is a major antiepileptic drug (AED) that is less potent than other AEDs. "	( Synthesis and anticonvulsant evaluation of dimethylethanolamine analogues of valproic acid and its tetramethylcyclopropyl analogue. Bialer, M; Shekh-Ahmad, T; Yavin, E, 2012)	2.05
"Valproic acid is a rare cause of eosinophilic pleural effusion."	( [Eosinophilic pleural effusion related to taking valproic acid]. Bally, C; Burgel, PR; Dusser, D; Kanaan, R; Kraoua, S; Lacronique, J; Martin, C, 2011)	1.34
"Valproic acid (VPA) is a potential anticancer agent that belongs to a class of histone deacetylase (HDAC) inhibitors, targeting the epigenetic control of gene functions in cancer cells."	( Effect of valproic acid on the outcome of glioblastoma multiforme. Chen, PY; Chen, SM; Huang, YC; Lee, ST; Lu, YJ; Tsai, CN; Tsai, HC; Wei, KC, 2012)	1.5
"Valproic acid (VPA) is a widely used anticonvulsant drug which affects mitochondrial metabolism including the catabolism of fatty acids and branched-chain amino acids."	( Inhibition of 3-methylcrotonyl-CoA carboxylase explains the increased excretion of 3-hydroxyisovaleric acid in valproate-treated patients. de Almeida, IT; Diogo, L; Duran, M; Garcia, P; IJlst, L; Luís, PB; Ruiter, JP; Silva, MF; Wanders, RJ, 2012)	1.82
"Valproic acid (VPA) is a potent anticonvulsant that inhibits histone deacetylases. "	( Chromatin remodeling, cell proliferation and cell death in valproic acid-treated HeLa cells. Felisbino, MB; Mello, ML; Tamashiro, WM, 2011)	2.06
"Valproic acid (VPA) is an anticonvulsant used to treat bipolar disorder, a psychiatric disease associated with disturbances in circadian rhythmicity. "	( Valproic acid phase shifts the rhythmic expression of Period2::Luciferase. Brask, J; Hetta, J; Johansson, AS; Lundkvist, GB; Owe-Larsson, B, 2011)	3.25
"Valproic acid (VA) is an antiepileptic drug, and frequently prescribed in pediatrics. "	( [The clinical course of a three year-old girl after overdose of valproic acid]. Blicher, TM; Dalhoff, KP; Vestergaard, ET, 2012)	2.06
"Valproic acid (VPA) is a short-chain branched fatty acid with anti-inflammatory, neuro-protective and axon remodeling effects. "	( Valproic acid ameliorates inflammation in experimental autoimmune encephalomyelitis rats. Schluesener, HJ; Wu, Y; Zhang, Z; Zhang, ZY, 2012)	3.26
"Valproic acid (VPA) is a histone deacetylase inhibitor."	( Effects of valproic acid, a histone deacetylase inhibitor, on improvement of locomotor function in rat spinal cord injury based on epigenetic science. Abdanipour, A; Schluesener, HJ; Tiraihi, T, 2012)	1.49
"Valproic acid (VPA), which is an effective antiepileptic drug, is known to inhibit the histone deacetylase activities."	( Enhanced antitumor efficacy of telomerase-specific oncolytic adenovirus with valproic acid against human cancer cells. Fujiwara, T; Hashimoto, Y; Kagawa, S; Kawamura, H; Nagai, K; Tanaka, N; Urata, Y; Watanabe, Y, 2012)	1.33
"Valproic acid (VA) is a histone deacetylase (HDAC) inhibitor that promotes self-renewal and expansion of hematopoietic stem cells and facilitates the generation of induced pluripotent stem cells from somatic cells and is currently being investigated in breast cancer clinical trials."	( Histone deacetylase inhibitors stimulate dedifferentiation of human breast cancer cells through WNT/β-catenin signaling. Atkinson, R; Buchholz, TA; Debeb, BG; Krishnamurthy, S; Lacerda, L; Larson, R; Reuben, JM; Solley, T; Sulman, EP; Ueno, NT; Woodward, WA; Xu, W, 2012)	1.1
"Valproic acid (VPA) is an antiepileptic and anti-migraine prophylactic drug. "	( Valproic acid downregulates RBP4 and elicits hypervitaminosis A-teratogenesis--a kinetic analysis on retinol/retinoic acid homeostatic system. Chang, CH; Chen, KC; Chuang, CM; Hsieh, CL; Peng, CC; Peng, RY; Wang, HE, 2012)	3.26
"Valproic acid (VPA) is a widely used mood stabilizer and antiepileptic drug."	( Valproic acid attenuates neuronal loss in the brain of APP/PS1 double transgenic Alzheimer's disease mice model. Chu, Y; He, G; Long, Z; Song, C; Song, W; Xie, P; Zhao, L; Zheng, M, 2013)	2.55
"Valproic acid (VPA) is a widely-used anticonvulsant and mood-stabilizing agent. "	( Valproate activates ERK signaling pathway in primary human hepatocytes. Bitman, M; Dvorak, Z; Pavek, P; Vrzal, R, 2014)	1.85
"Valproic acid (VPA) is a potent inducer of neural tube defects in human and mouse, its teratogenicity is associated with its potential to generation of free radicals and increase oxidative stress. "	( Spirulina (arthrospira) protects against valproic acid-induced neural tube defects in mice. Chamorro-Cevallos, G; Escalona-Cardoso, GN; Paniagua-Castro, N; Pérez-Pastén, R, 2012)	2.09
"Valproic acid (VPA) is a commonly used antiepileptic drug that acts on these signaling pathways; however, the effect of VPA on cutaneous wound healing is unknown."	( Valproic acid induces cutaneous wound healing in vivo and enhances keratinocyte motility. Choi, KY; Hwang, JK; Lee, SH; Min, do S; Zahoor, M, 2012)	2.54
"Valproic acid (VPA) is an anti-epileptic and mood-stabilizing compound successfully used in the clinics since many decades. "	( Cardio-hepatic metabolic derangements and valproic acid. Longhitano, C; Mazzoccoli, G; Vinciguerra, M, 2014)	2.11
"Valproic acid (VPA), which is a commonly used drug in the treatment of epilepsy, has been reported to have neuroprotective effects against various neuronal insults including ischemic stroke."	( Neuroprotective effects of valproic acid against hemin toxicity: possible involvement of the down-regulation of heme oxygenase-1 by regulating ubiquitin-proteasomal pathway. Cheong, JH; Cho, KS; Han, SH; Han, SY; Ignarro, LJ; Jeon, SJ; Kim, HY; Kim, JN; Kim, MK; Kim, SY; Kwon, KJ; Ryu, JH; Shin, CY, 2013)	1.41
"Valproic acid (VPA) is a short-chained, branched fatty acid that is widely used in humans as an anticonvulsant and mood stabilizer, and has been reported to increase the liver NAD concentration. "	( Increased conversion of tryptophan to nicotinamide in rats by dietary valproate. Fukuwatari, T; Kondo, R; Sano, M; Shibata, K, 2013)	1.83
"Valproic acid is a widely used drug in the treatment of epilepsy and, compared to other anticonvulsant drugs, is considered safe. "	( Pathological case of the month: sudden death in a child as a result of pancreatitis during valproic acid therapy. Donoghue, ER; Lifschultz, BD; Mileusnic, D, )	1.79
"Valproic acid (VPA) is an anticonvulsant drug that induces neural tube and related defects."	( Neural crest cell motility in valproic acid. Cornelius, SK; Fuller, LC; Murphy, CW; Wiens, DJ, )	1.14
"Valproic acid (VPA) is an effective anticonvulsant useful in many types of epilepsy and, although it is usually well tolerated, it has been associated with many neurological and systemic side effects. "	( Valproate-induced hyperammonemic encephalopathy. Chiarelli, F; Morgese, G; Trotta, D; Verrotti, A, 2002)	1.76
"Valproic acid (VPA) is an antiepileptic drug (AED) used for generalized and absence seizures. "	( Effects of age and polytherapy, risk factors of valproic acid (VPA) hepatotoxicity, on the excretion of thiol conjugates of (E)-2,4-diene VPA in people with epilepsy taking VPA. Abbott, F; Farrell, K; Gopaul, S, 2003)	2.02
"Valproic acid (VPA) is a branched-chain fatty acid that is able to inhibit growth of human and rodent tumor cells and to induce a mature phenotype."	( Increase of fetal hemoglobin synthesis indicating differentiation induction in children receiving valproic acid. Cinatl, J; Driever, PH; Kieslich, M; Schwabe, D, )	1.07
"Valproic acid (VPA) is a commonly prescribed medication approved for use in the United States for epilepsy, migraine, and bipolar disorder. "	( Acute pancreatitis in children from Valproic acid: case series and review. Feldman-Winter, LB; Goldfarb, O; Grauso-Eby, NL; McAbee, GN, 2003)	2.04
"Valproic acid (VPA) is an antiepileptic drug with mood-stabilizing properties."	( Search for a common mechanism of mood stabilizers. Agam, G; Harwood, AJ, 2003)	1.04
"Valproic acid is a carboxylic acid used for the treatment of both seizure and mood disorders. "	( Valproic acid-induced eosinophilic pleural effusion. Federman, DG; Kravetz, JD, 2003)	3.2
"Valproic acid is a short branched fatty acid used as an anticonvulsant drug whose therapeutic action has been proposed to arise from membrane-disordering properties. "	( Permeation across hydrated DPPC lipid bilayers: simulation of the titrable amphiphilic drug valproic acid. Haymet, AD; Ulander, J, 2003)	1.98
"Valproic acid (VPA) is a commonly used anticonvulsant with multiple systemic effects. "	( Valproic acid blood genomic expression patterns in children with epilepsy - a pilot study. Ficker, DM; Gilbert, DL; Glauser, TA; Hershey, AD; Privitera, MD; Sharp, FR; Szaflarski, JP; Tang, Y, 2004)	3.21
"Valproic acid (VPA) is a widely used antiepileptic agent that is undergoing clinical evaluation for anticancer therapy. "	( Valproic acid inhibits angiogenesis in vitro and in vivo. Blaheta, RA; Busse, R; Cinatl, J; Fleming, I; Hoffmann, K; Kotchetkov, R; Michaelis, M; Michaelis, UR; Nau, H; Suhan, T, 2004)	3.21
"Valproic acid (VPA) is an effective antiepileptic medication, the use of which in females of childbearing age is complicated by its ability to induce birth defects, including neural tube defects (NTDs), in exposed embryos. "	( Teratogenicity of valproate conjugates with anticonvulsant activity in mice. Alexander, G; Chatterjie, N; Finnell, RH; Spiegelstein, O, 2003)	1.76
"Valproic acid (VPA) is a major therapeutic agent in the treatment of epilepsy and other neurological disorders. "	( Abolition of valproate-derived choleresis in the Mrp2 transporter-deficient rat. Dickinson, RG; Wright, AW, 2004)	1.77
"Valproic acid (VPA) is an antiepileptic drug used clinically. "	( Effect of valproic acid on fetal and maternal organs in the mouse: a morphological study. Emmanouil-Nikoloussi, EN; Foroglou, NG; Kerameos-Foroglou, CH; Thliveris, JA, 2004)	2.17
"Valproic acid is an effective and safe drug in the treatment of Sydenham's chorea."	( Sydenham's chorea-clinical characteristics of nine patients. Davutoglu, V; Dinckal, H; Kilinc, M; Sezen, Y; Soydinc, S, 2004)	1.04
"Valproic acid (VA) is a well-tolerated drug used to treat seizure disorders and has recently been shown to inhibit histone deacetylase (HDAC). "	( Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid. Burgan, WE; Camphausen, K; Cerna, D; Cerra, MA; Fine, H; Scott, T; Sproull, M; Tofilon, PJ, 2005)	2.01
"Valproic acid (VPA) is an anti-epileptic drug that has been associated with polycystic ovary syndrome (PCOS)-like symptoms, including increased ovarian androgen production. "	( Valproate-induced alterations in human theca cell gene expression: clues to the association between valproate use and metabolic side effects. Jansen, E; McAllister, JM; Mosselman, S; Nelson-Degrave, VL; Strauss, JF; Wood, JR, 2005)	1.77
"Valproic acid (VPA) is a very effective anticonvulsant agent widely used in the management of various forms of epilepsy."	( Effect of long-term therapy with sodium valproate on nail and serum trace element status in epileptic children. Akyol, O; Armutcu, F; Gurel, A; Kanter, M; Ozerol, E; Vural, H; Yakinci, C, 2004)	1.04
"Valproic acid is a safe and widely used neurologic agent that acts as a potent inhibitor of histone deacetylase activities."	( Histone deacetylase inhibitor valproic acid enhances the cytokine-induced expansion of human hematopoietic stem cells. Agostini, F; Arcese, W; De Felice, L; Fiorini, R; Gelmetti, V; Gregorj, C; Mascolo, MG; Nervi, C; Padula, F; Pascale, S; Petrucci, MT; Tatarelli, C, 2005)	1.34
"Valproic acid is an anticonvulsant that requires careful therapeutic drug monitoring. "	( Analytical performance evaluation of a new turbidimetric immunoassay for valproic acid on the ADVIA 1650 analyzer: effect of gross hemolysis and high bilirubin. Dasgupta, A; Datta, P, 2005)	2
"Valproic acid is an anticonvulsant drug which is associated with serious toxicity including fatal outcome in case of severe intoxication. "	( Severe valproic acid intoxication is associated with atrial tachycardia: secondary detoxication by hemoperfusion. Kuhlmann, MK; Limbach, HG; Lindinger, A; Meyer, S; Peters, FT, )	2.03
"Valproic acid (VPA) is a widely used treatment for both epilepsy and bipolar disorders, although its therapeutic mechanism of action is not fully understood. "	( Reduced anticonvulsant efficacy of valproic acid in dopamine beta-hydroxylase knockout mice. Liles, LC; Schank, JR; Weinshenker, D, 2005)	2.05
"Valproic acid (VPA) is a widely used anticonvulsant medication with well-known teratogenic effects in both humans and in experimental animal model systems. "	( Valproic acid-induced skeletal malformations: associated gene expression cascades. Cabrera, RM; Finnell, RH; Giavini, E; Massa, V; Menegola, E, 2005)	3.21
"Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well tolerated, but rare serious complications may occur in some patients receiving VPA chronically, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity (VHT) and VPA-induced hyperammonaemic encephalopathy (VHE). "	( Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence? Gris, M; Lheureux, PE; Penaloza, A; Zahir, S, 2005)	2.03
"Valproic acid (VPA) is a potent anti-epileptic and effective mood stabilizer. "	( Novel targets for valproic acid: up-regulation of melatonin receptors and neurotrophic factors in C6 glioma cells. Castro, LM; Gallant, M; Niles, LP, 2005)	2.1
"Valproic acid (VA) is an anticonvulsant that inhibits histone deacetylase activity at nontoxic concentrations."	( Valproic acid inhibits growth, induces apoptosis, and modulates apoptosis-regulatory and differentiation gene expression in human thyroid cancer cells. Chung, WY; Clark, OH; Duh, QY; Kebebew, E; Shen, WT; Wong, MG; Wong, TS, 2005)	2.49
"Valproic acid is a well-tolerated anticonvulsant that has been identified recently as a histone deacetylase inhibitor. "	( Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expression of p21Cip1, CDK4, and CMYC. Blaney, SM; Lau, CC; Li, XN; Perlaky, L; Shu, Q; Su, JM, 2005)	3.21
"Valproic acid (VPA) is a common drug used in the treatment of epilepsy."	( [Experimental study on the mechanism of the apoptosis of leukemic cells induced by valproic acid]. Chen, Q; Guo, HX; Li, WY; Liu, Y; Xia, Y; Xue, HM, 2005)	1.27
"Valproic acid (VPA) is a psychoactive drug currently used for the treatment of epilepsy. "	( Sodium- and magnesium-valproate in vivo modulate glutamatergic and GABAergic synapses in the medial prefrontal cortex. Gobbi, G; Janiri, L, 2006)	1.78
"Valproic acid (VPA) is an anticonvulsant drug that is widely used therapeutically for a variety of neurological conditions. "	( Myo-inositol enhances teratogenicity of valproic acid in the mouse. Finnell, RH; Giavini, E; Massa, V; Wlodarczyk, B, 2006)	2.04
"Valproic acid (VPA) is an antiepileptic drug widely used and well-tolerated by most of patients. "	( Serum and liver tissue biotinidase enzyme activity in rats which were administrated to valproic acid. Akin, R; Demirkaya, E; Gokcay, E; Korkmazer, N; Kul, M; Unay, B; Vurucu, S, 2006)	2
"Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. "	( Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children. Augspach-Hofmann, R; Bendl, C; Buesing, D; Fitzek, S; Gerstner, T; Goetze, G; Haensch, CA; Klostermann, W; Koenig, SA; Lippert, G; Longin, E; Macke, A; Mayer, G; Reuland, M; Scheid, B; Wenzel, D, 2006)	3.22
"Valproic acid (VPA) is a widely used anticonvulsive agent that has profound antiproliferative effects in many cell types, as well as inductive effects on a number of genes. "	( Valproic acid-induced gene expression through production of reactive oxygen species. Arinze, IJ; Kawai, Y, 2006)	3.22
"Valproic acid (VPA) is an established drug in the long-term therapy of seizure disorders. "	( Chronic administration of valproic acid inhibits prostate cancer cell growth in vitro and in vivo. Carducci, M; Chen, CL; Chowdhury, W; Höti, N; Rodriguez, R; Shabbeer, S; Sung, J; Xia, Q, 2006)	2.08
"Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for generalized and focal epilepsies. "	( Valproate-associated coagulopathies are frequent and variable in children. Bell, N; Brand, J; Dempfle, CE; Gerstner, T; König, S; Longin, E; Teich, M, 2006)	1.78
"Valproic acid (VPA) is a commonly used medication approved by the U.S. "	( [Sodium valproate as a cause of acute pancreatitis: a case report]. Barreda, L; Milian, W; Rosas, J; Targarona, J; Valdivia, D, )	1.57
"Valproic acid is a well-known antiepileptic drug that was recently discovered to have a wide-spectrum antitumoral action in several tumors. "	( Valproic acid induces apoptosis in prostate carcinoma cell lines by activation of multiple death pathways. Angelucci, A; Bernardini, S; Bologna, M; Dolo, V; Federici, G; Gravina, GL; Miano, R; Millimaggi, D; Valentini, A; Vicentini, C, 2006)	3.22
"Valproic acid (VPA) is an effective antiepileptic drug with an additional activity for the treatment of bipolar disorder. "	( The effects of central nervous system-active valproic acid constitutional isomers, cyclopropyl analogs, and amide derivatives on neuronal growth cone behavior. Bialer, M; Dalton, EC; Ewan, K; Eyal, S; Harwood, AJ; Jenkins, A; Pessah, N; Shimshoni, JA; Williams, RS; Yagen, B, 2007)	2.04
"Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for generalized and focal epilepsies. "	( Valproic acid-induced hepatopathy: nine new fatalities in Germany from 1994 to 2003. Borusiak, P; Boxtermann, W; Brückner, R; Buesing, D; Degen, I; Degenhardt, V; Fitzek, S; Gerstner, T; Haensch, CA; Hanusch, R; Hartmann, M; Häussermann, P; Hoppen, T; Jungck, A; Kasper, JM; Kluger, G; Knapp, R; Koenig, SA; Korenke, GC; Kuhn, H; Lindmayer, F; Longin, E; Müller-Deile, A; Oehring, R; Richard, HH; Samii, K; Seitz, R; Specht, U; Weber, Y; Weidner, B, 2006)	3.22
"Valproic acid is an effective anti-epileptic medication often used for long-term control of seizure disorders that has been implicated in hematological toxicities, including rare reports of myelodysplasia and acute leukemia. "	( Translocation-positive acute myeloid leukemia associated with valproic acid therapy. Ben-Ezra, J; Massey, GV; Riley, RS; Russell, EC; Williams, DC, 2008)	2.03
"Valproic acid is a hepatically metabolised, low extraction-ratio drug."	( Effect of time, injury, age and ethanol on interpatient variability in valproic acid pharmacokinetics after traumatic brain injury. Anderson, GD; Awan, AB; Temkin, NR; Winn, HR; Winn, RH, 2007)	1.29
"Valproic acid (VPA), is a drug approved by the FDA for epilepsy and bipolar disorders. "	( Multiple Molecular pathways explain the anti-proliferative effect of valproic acid on prostate cancer cells in vitro and in vivo. Carducci, MA; Galloway, N; Kachhap, S; Kortenhorst, MS; Rodriguez, R; Shabbeer, S, 2007)	2.02
"Valproic acid is a widely used anticonvulsant that has recently been approved for stabilization of manic episodes in patients with bipolar disorder. "	( Carnitine as an antidote for acute valproate toxicity in children. Russell, S, 2007)	1.78
"Valproic acid is a widely used anticonvulsant drug with a broad therapeutic spectrum."	( Inhibitory effect of valproic acid on cytochrome P450 2C9 activity in epilepsy patients. Babaoglu, MO; Bilir, E; Bozkurt, A; Gunes, A; Yasar, U; Zengil, H, 2007)	1.38
"Valproic acid (VPA) is an antiepileptic drug frequently used in children. "	( Severe bleeding complications during antiepileptic treatment with valproic acid in children. Albisetti, M; Cannizzaro, E; Schmugge, M; Wohlrab, G, 2007)	2.02
"Valproic acid (VPA) is a powerful teratogen causing birth defects in humans, including autism spectrum disorder (ASD), if exposure occurs during the first trimester of embryogenesis. "	( Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid. Antoniello, K; Kulangara, K; Markram, H; Rinaldi, T, 2007)	1.99
"Valproic acid is an established therapeutic for a variety of seizure disorders and in certain cases for depression and anxiety. "	( The epigenetic modifier, valproic acid, enhances radiation sensitivity. El-Osta, A; Karagiannis, TC; Kn, H, )	1.88
"Valproic acid (VPA) is a commonly prescribed anticonvulsant drug for the treatment of various forms of epilepsy. "	( [Seven cases of decreased serum valproic acid concentration during concomitant use of carbapenem antibiotics]. Joo, JY; Kim, JH; Kwon, OH; Lee, SG, 2007)	2.07
"Valproic acid is a small carboxylic acid that is the most frequently prescribed anticonvulsant drug in humans."	( Valproic acid extends Caenorhabditis elegans lifespan. Collins, JJ; Evason, K; Huang, C; Hughes, S; Kornfeld, K, 2008)	2.51
"Valproic acid (VPA) is a promising anticancer agent recently assigned to the class of histone deacetylase (HDAC) inhibitors."	( Neuroendocrine transdifferentiation induced by VPA is mediated by PPARgamma activation and confers resistance to antiblastic therapy in prostate carcinoma. Angelucci, A; Bologna, M; Cerù, MP; Cimini, A; Cristiano, L; Dolo, V; Miano, R; Millimaggi, D; Muzi, P; Vicentini, C, 2008)	1.07
"Valproic acid (VPA) is an effective and widely used anticonvulsant, associated with metabolic adverse effects such as weight gain, hyperinsulinemia, hyperleptinemia and hypoadiponectinemia. "	( Adiponectin receptor R1 is upregulated by valproic acid but not by topiramate in human hepatoma cell line, HepG2. Ciardi, C; Ebenbichler, CF; Engl, J; Kaser, S; Laimer, M; Lechleitner, M; Luef, G; Patsch, J; Rauchenzauner, M; Tatarczyk, T; Tschoner, A, 2008)	2.05
"Valproic acid (VPA) is an effective antiepileptic drug and mood stabilizer. "	( Enhanced rat sciatic nerve regeneration through silicon tubes implanted with valproic acid. Peng, Z; Rao, T; Wu, F; Xing, D, 2008)	2.02
"Valproic acid (VPA) is a simple fatty acid largely used as anticonvulsivant agent. "	( Early structural and functional changes in liver of rats treated with a single dose of valproic acid. Bonazzi, P; Jezequel, AM; Novelli, G; Orlandi, F; Venturini, C, )	1.8
"Valproic acid (VPA) is an anticonvulsant agent which produced marked choleresis in the rat. "	( Choleretic effect of valproic acid in the rat. Klaassen, CD; Watkins, JB, )	1.89
"Valproic acid is a branched-chained fatty acid, structurally unrelated to any other antiepileptic drug. "	( Valproic acid. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy. Davis, R; McTavish, D; Peters, DH, 1994)	3.17
"Valproic acid (VPA) is a fatty acid antiepileptic with demonstrated antimanic properties, but the molecular mechanism or mechanisms underlying its therapeutic efficacy remain to be elucidated. "	( Chronic sodium valproate selectively decreases protein kinase C alpha and epsilon in vitro. Chen, G; Hawver, DB; Manji, HK; Potter, WZ; Wright, CB, 1994)	1.73
"Valproic acid is a useful antiepileptic drug, with occasional gastrointestinal side effects. "	( [Hepatotoxicity induced by valproic acid in adults. Report of 3 cases]. Aguilera, L; Chesta, J; Galdames, D; Silva, C, 1993)	2.03
"Valproic acid (VPA) is an antiepileptic drug that crosses the placenta freely. "	( Placental transfer of valproic acid after liposome encapsulation during in vitro human placenta perfusion. Algeri, M; Barzago, MM; Bonati, M; Bortolotti, A; Diomede, L; Efrati, S; Salmona, M; Stellari, FF, 1996)	2.05
"Valproic acid (VPA) is an anti-convulsant drug known to cause spina bifida in humans. "	( Effect of supplemental folic acid on valproic acid-induced embryotoxicity and tissue zinc levels in vivo. Dial, SL; Gehring, TA; Grafton, TF; Hansen, DK; Siitonen, PH, 1995)	2.01
"Valproic acid (VPA) is an anticonvulsant drug with demonstrated efficacy in the treatment of mania. "	( Effects of valproic acid on beta-adrenergic receptors, G-proteins, and adenylyl cyclase in rat C6 glioma cells. Chen, G; Hawver, DB; Manji, HK; Potter, WZ; Wright, CB, 1996)	2.13
"Valproic acid is an anticonvulsant that is strongly bound to serum albumin. "	( Interaction of valproic acid with nonsteroidal antiinflammatory drugs mefenamic acid and fenoprofen in normal and uremic sera: lack of interaction in uremic sera due to the presence of endogenous factors. Dasgupta, A; Emerson, L, 1996)	2.09
"Valproic acid (VPA) is a simple branched-chain fatty acid that has anticonvulsant activity and is widely used in the treatment of epilepsy. "	( Antitumor activity of sodium valproate in cultures of human neuroblastoma cells. Cinatl, J; Doerr, HW; Driever, PH; Henrich, D; Kabickova, H; Kornhuber, B; Scholz, M; Vogel, JU, 1996)	1.74
"Valproic acid is an anticonvulsant drug known to inhibit the glucuronidation of zidovudine (AZT) in human liver microsomes. "	( Valproic acid increases cerebrospinal fluid zidovudine levels in a patient with AIDS. Akula, SK; Dejace, PM; Dreisbach, AW; Lertora, JJ; Rege, AB, 1997)	3.18
"Valproic acid is an antiepileptic drug in widespread use. "	( Thrombocytopenic purpura and anemia in a breast-fed infant whose mother was treated with valproic acid. Neiderud, J; Stahl, MM; Vinge, E, 1997)	1.96
"Valproic acid (VPA) is a commonly used antiepileptic agent that recently has been found useful in the treatment of affective disorders and prophylaxis of migraine. "	( Valproate-induced limb malformations in mice associated with reduction of intracellular pH. Beliles, RP; Colvin, J; McCandless, D; Nau, H; Schreiner, CM; Scott, WJ; Vorhees, CV, )	1.57
"Valproic acid is an effective antiseizure medication that is also used for other indications such as migraine prophylaxis. "	( Multiorgan system failure caused by valproic acid toxicity. Pinkston, R; Walker, LA, 1997)	2.01
"Valproic acid (VPA) is an antiepileptic drug widely used in paediatrics. "	( [Evaluation of the effect of long term valproic acid treatment on plasma levels of carnitine, ammonia and amino acids related to the urea cycle in pediatric epileptic patients]. Jiménez, C; Lluch-Fernández, MD; Marchante-Serrano, C; Navarro-Quesada, FJ; Vaquero-Abellán, M, 1997)	2.01
"Valproic acid (VPA) is a frequently used anti-epileptic drug that has a potentially teratogenic character, as well as the capacity for inducing NTD and other less serious malformations."	( [Morphological changes induced by valproate and its administration concomitant with folinic acid or S-adenosylmethionine in pregnant rats]. Achón, M; Alonso-Aperte, E; Pérez de Miguelsanz, J; Puerta, J; Ubeda-Martín, N; Varela-Moreiras, G, )	0.85
"Valproic acid (VPA) is an established human teratogen that causes neural tube defects in 1-2% of human foetuses exposed to the drug during early pregnancy. "	( Cell motility is inhibited by the antiepileptic compound, valproic acid and its teratogenic analogues. Berezin, A; Berezin, V; Bock, E; Ellerbeck, U; Foley, A; Nau, H; Walmod, PS, 1998)	1.99
"Valproic acid (VPA) is a potent broad spectrum anticonvulsant with demonstrated efficacy in the treatment of Bipolar Affective Disorder, but the biochemical basis for VPA's antimanic or mood-stabilizing actions have not been fully elucidated. "	( Valproate robustly enhances AP-1 mediated gene expression. Chen, G; Huang, LD; Jiang, YM; Manji, HK; Yuan, PX, 1999)	1.75
"Valproic acid (VPA) is a potent broad-spectrum anti-epileptic with demonstrated efficacy in the treatment of bipolar affective disorder. "	( The mood-stabilizing agent valproate inhibits the activity of glycogen synthase kinase-3. Chen, G; Huang, LD; Jiang, YM; Manji, HK, 1999)	1.75
"Valproic acid is an effective treatment for mania."	( Sodium valproate increases pupillary responsiveness to a cholinergic agonist in responders with mania. DeMet, EM; Sokolski, KN, 1999)	1.02
"Valproic acid (VPA) is a branched chain fatty acid that is able to inhibit proliferation of neuroectodermal cells and to induce these cells along neuronal or glial lineage."	( Valproic acid for the treatment of pediatric malignant glioma. Cinatl, J; Driever, PH; Knüpfer, MM; Wolff, JE, )	2.3
"Valproic acid (VPA) is an anticonvulsive drug used in the treatment of epilepsy. "	( Action of valproic acid on Xenopus laevis development: teratogenic effects on eyes. de Bernardi, F; Groppelli, S; Pennati, R; Sotgia, C, 2001)	2.16
"Valproic acid is an anticonvulsant widely used for the treatment of epilepsy. "	( Uptake mechanism of valproic acid in human placental choriocarcinoma cell line (BeWo). Matsuo, H; Nakano, H; Ohtani, H; Sawada, Y; Takanaga, H; Tsukimori, K; Ushigome, F, 2001)	2.08
"Valproic acid (VPA) is a short, branched fatty acid with broad-spectrum anticonvulsant activity. "	( Continuum solvent model studies of the interactions of an anticonvulsant drug with a lipid bilayer. Ben-Tal, N; Kessel, A; Musafia, B, 2001)	1.75
"Valproic acid (VPA) is an effective antiepileptic drug (AED), which is associated with dose-related adverse reactions such as skin rash, hair loss (alopecia), etc. "	( Low serum biotinidase activity in children with valproic acid monotherapy. Karikas, GA; Regoutas, S; Schulpis, KH; Tjamouranis, J; Tsakiris, S, 2001)	2.01
"Valproic acid (VPA) is a broad-spectrum anticonvulsant with well-documented teratogenic effects, but whose mechanism of action is largely unknown. "	( A role for protein kinase C and its substrates in the action of valproic acid in the brain: implications for neural plasticity. Lenox, RH; Meyer, EM; Watson, DG; Watterson, JM, 2002)	2
"Valproic acid is a new antiepileptic drug recently introduced in the United States for the treatment of absence seizures. "	( Clinical efficacy of valproic acid in relation to plasma levels. Bruni, J; Crawford, LE; Thomas, M; Villarreal, HJ; Wilder, BJ; Willmore, LJ, 1978)	2.02
"Valproic acid is a new antiepileptic drug. "	( Valproic acid. Review of a new antiepileptic drug. Bruni, J; Wilder, BJ, 1979)	3.15
"Valproic acid is a promising antiepileptic drug with broad-spectrum activity, and is particularly useful in the treatment of absence and myoclonic seizures, although further clinical experience is required before it can supplant ethosuximide as the preferred drug for the treatment of absence seizures."	( Recent advances in drug therapy for epilepsy. Bruni, J, 1979)	0.98
"Valproic acid is a commonly used drug for the treatment of epilepsy. "	( Absorption of valproic acid from the gastrointestinal tract of the piglet. Ailabouni, A; Breech, L; Murray, RD; Nahata, MC, )	1.93
"Valproic Acid (VPA) is an important drug for the treatment of several types of seizures because it has a wide spectrum of activity. "	( Determination of free valproic acid: evaluation of the Centrifree system and comparison between high-performance liquid chromatography and enzyme immunoassay. Barham, CF; Delgado, M; Eggers, CM; Forman, LJ; Liu, H; Montoya, JL, 1992)	2.04
"Valproic acid is a very effective anticonvulsant agent widely used in the management of various forms of epilepsy. "	( Developmental toxicity of valproic acid. Cotariu, D; Zaidman, JL, 1991)	2.02
"(1) Valproic acid is an anticonvulsant agent widely used in the management of various forms of epilepsy, including absence, myoclonic and tonic-clonic seizures. "	( Neurophysiological and biochemical changes evoked by valproic acid in the central nervous system. Cotariu, D; Evans, S; Zaidman, JL, 1990)	1.09
"Valproic acid (VPA) is an antiepileptic drug used in the treatment of a wide variety of human seizures including generalized absence (GA) (petit mal) seizures. "	( Valproic acid selectively reduces the low-threshold (T) calcium current in rat nodose neurons. Gross, RA; Kelly, KM; Macdonald, RL, 1990)	3.16
"Valproic acid is an anticonvulsant that has been associated with open neural tube defects. "	( Valproic acid prenatal exposure. Association with lipomyelomeningocele. Carter, BS; Stewart, JM, 1989)	3.16
"Valproic acid, which is an isomer of 2-EXHA, also produced similar defects, and was approximately twice as potent as 2-EHXA."	( Teratogenicity of di(2-ethylhexyl) phthalate, 2-ethylhexanol, 2-ethylhexanoic acid, and valproic acid, and potentiation by caffeine. Randall, JL; Ritter, EJ; Ritter, JM; Scott, WJ, 1987)	1.22
"Valproic acid is a reliable and comparatively safe drug in the treatment of special forms of absence seizures. "	( [Unapparent course of pancreatitis with pseudocyst development and cholestatic jaundice in anticonvulsive therapy with valproate]. Braun, E; Bundschu, HD; Spannagel, B, 1987)	1.72
"Valproic acid is an effective broad spectrum anticonvulsant drug. "	( Concentration-effect relationships of valproic acid. Chadwick, DW, )	1.85
"Valproic acid is a very commonly used anti-epileptic drug which requires regular monitoring. "	( [Valproic acid, a comparison between 2 methods of determination: immunoenzymology and high performance liquid chromatography]. Batten, J; Bugugnani, MJ; Fouyé, H; Richard, L, 1985)	2.62

Effects

Valproic acid (VPA) has a narrow therapeutic range (50-100mg/l) and exhibits nonlinear protein binding. The drug also has a demonstrated efficacy in the preventive treatment of migraine with and without aura.

Valproic acid (VPA) has emerged as an anticancer drug via inhibition of histone deacetylases (HDACs) It poses a neurodevelopmental risk due to its high teratogenicity. Long-term use of VPA is regularly accompanied by hematological toxicity.

Excerpt	Reference	Relevance
"Valproic acid has a long-standing reputation of effectively treating the symptoms of not only epilepsy but also psychiatric conditions. "	( Valproic acid potently inhibits interictal-like epileptiform activity in prefrontal cortex pyramidal neurons. Nurowska, E; Pasierski, M; Szulczyk, B, 2019)	3.4
"Valproic acid (VPA) has an extensive interindividual pharmacokinetic variability. "	( Impact of age, gender and CYP2C9/2C19 genotypes on dose-adjusted steady-state serum concentrations of valproic acid-a large-scale study based on naturalistic therapeutic drug monitoring data. Haslemo, T; Molden, E; Refsum, H; Smith, RL, 2016)	2.09
"• Valproic acid has a cumulative effect on inhibiting brain activity in epileptogenic regions."	( Resting-state fMRI revealed different brain activities responding to valproic acid and levetiracetam in benign epilepsy with central-temporal spikes. Dante, M; Hu, Z; Li, K; Li, Q; Li, Z; Lu, G; Wu, H; Xu, Q; Yang, F; Zhang, Q; Zhang, Z, 2017)	1.25
"Valproic acid also has a demonstrated efficacy in the preventive treatment of migraine with and without aura, but its tolerability profile and the possibility of serious adverse events oblige us to prescribe this neuromodulator for refractory patients."	( [The role of the neuromodulators in the preventive treatment of migraine]. Pascual-Gómez, J, )	0.85
"Valproic acid (VPA) has a narrow therapeutic range (50-100mg/l) and exhibits nonlinear protein binding. "	( Oral/intravenous maintenance dosing of valproate following intravenous loading: a simulation. Cloyd, JC; Collins, SD; Dutta, S; Granneman, GR, 2003)	1.76
"Valproic acid (VPA), which has a wide range of therapeutic applications, is known as a potent teratogen that induces neural tube defects in vertebrates. "	( A novel embryotoxic estimation method of VPA using ES cells differentiation system. Fujiwara, Y; Hiroyama, M; Murabe, M; Sanbe, A; Tanoue, A; Yamauchi, J, 2007)	1.78
"Valproic acid has a wider antiepileptic spectrum than any other antiepileptic drug (AED) in clinical use. "	( [Sodium valproate--current status of pharmacological research]. Chapman, AG, 1994)	1.73
"Valproic acid (VPA) has been widely used to prevent epileptic seizures after neurosurgery in China. "	( Valproic Acid After Neurosurgery Induces Elevated Risk of Liver Injury: A Prospective Nested Case-Control Study. Guo, J; Ji, H; Li, X; Li, Y; Ma, J; Peng, F; Sun, Y; Wang, S, 2022)	3.61
"Valproic acid (VPA) has shown beneficial effects in vitro against SARS-CoV-2 infection, but no study has analyzed its efficacy in the clinical setting."	( Exposure to valproic acid is associated with less pulmonary infiltrates and improvements in diverse clinical outcomes and laboratory parameters in patients hospitalized with COVID-19. Artero, A; Asensi, V; Asensi-Díaz, E; Blanes, R; Collazos, J; Domingo, P; Dueñas-Gutiérrez, C; Fernández-Araujo, N; Lalueza, A; Lamas-Ferreiro, JL; Ramos-Rincón, JM; Raya-Cruz, M; Roy-Vallejo, E; Sanz-Cánovas, J; Vilchez-Rueda, H, 2022)	2.54
"Valproic acid (VPA) has been used to treat epilepsy and bipolar disorder. "	( Valproic acid decreases vascular smooth muscle cell proliferation via protein phosphatase 2A-mediated p70 S6 kinase inhibition. Cho, DH; Hwang, YJ; Lee, H; Park, JH, 2022)	3.61
"Valproic acid (VPA) has been extensively used for treatment of anxiety and seizure. "	( Valproic acid during hypotensive resuscitation in pigs with trauma and hemorrhagic shock does not improve survival. Bynum, J; Cap, AP; Martini, WZ; Ryan, KL; Xia, H, 2022)	3.61
"Valproic acid (VPA) has been widely used for the treatment of epilepsy."	( Therapeutic Potential of Valproic Acid for Postviral Olfactory Dysfunction: A Single-Arm Pilot Study. Hira, D; Kikuoka, H; Matsumoto, K; Ogawa, T; Shimizu, T; Tojima, I, 2023)	1.93
"Valproic acid (VPA) has been extensively used for the treatment of seizures in epilepsy. "	( Design of self-assembling anti-epileptic drug for long-acting drug delivery Ikeda, Y; Nagasaki, Y; Tajika, Y, 2022)	2.16
"Valproic acid (VPA) has long been the most widely used antiepileptic drug (AED) for the treatment of epilepsy, bipolar psychiatric disorders, and migraine. "	( Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Chalmel, F; Costet, N; Desdoits-Lethimonier, C; Evrard, B; Hug, E; Jégou, B; Kugathas, I; Lavoué, V; Lesné, L; Mazaud-Guittot, S; Raffenne, L; Toupin, M, 2023)	2.35
"Valproic acid (VPA) has been widely used more frequently as its approved indications have been expanded. "	( Rhabdomyolysis and Hepatotoxicity From Valproic Acid: Case Reports. Deb, S; Walker, CP, 2021)	2.33
"Valproic acid has been proposed as an alternative agent for treatment of agitation and delirium in the intensive care unit (ICU). "	( Valproic Acid for the Management of Agitation and Delirium in the Intensive Care Setting: A Retrospective Analysis. Crowley, KE; Geiger, KL; Hacobian, G; Urben, L, 2020)	3.44
"Valproic acid (VPA) has been shown to attenuate brain lesion size and swelling within the first few hours following TBI."	( Pharmacologic modulation of brain metabolism by valproic acid can induce a neuroprotective environment. Alam, HB; Bhatti, UF; Biesterveld, BE; Dennahy, IS; Kachman, M; Karnovsky, A; Li, Y; Liu, B; Nikolian, VC; O'Connell, RL; Siddiqui, A; Williams, AM, 2021)	1.6
"Valproic acid (VPA) has attracted a lot of interest in cancer research."	( Apoptotic effects of valproic acid on miR-34a, miR-520h and HDAC1 gene in breast cancer. Amini-Farsani, Z; Injinari, N; Teimori, H; Yadollahi-Farsani, M, 2021)	1.66
"Valproic acid (VPA) has been used recently to treat agitation in delirium."	( Valproic Acid in the Management of Delirium. Cuartas, CF; Davis, M, 2022)	2.89
"Valproic acid has histone deacetylase (HDAC) inhibitory activity."	( Antimetastatic Efficacy of the Combination of Caffeine and Valproic Acid on an Orthotopic Human Osteosarcoma Cell Line Model in Nude Mice. Hayashi, K; Hoffman, RM; Igarashi, K; Kawaguchi, K; Kimura, H; Kiyuna, T; Miwa, S; Murakami, T; Tsuchiya, H; Yamamoto, N, 2017)	1.42
"Valproic acid (VPA) has been associated with improved outcomes in multiple models of trauma, when combined with isotonic fluid resuscitation."	( Lung Protective Effects of Low-Volume Resuscitation and Pharmacologic Treatment of Swine Subjected to Polytrauma and Hemorrhagic Shock. Alam, HB; Dennahy, IS; Duan, X; Duggan, MJ; Georgoff, PE; Li, Y; Liu, B; Mesar, T; Nikolian, VC; Pan, B; Wu, X, 2017)	1.18
"Valproic acid (VPA) has been widely used in Chinese patients after craniotomy. "	( Analysis of the Variables Influencing Valproic Acid Concentration in the Serum and Cerebrospinal Fluid of Chinese Patients After Craniotomy. Chen, W; Gao, W; Li, Z; Liu, G, 2017)	2.17
"Valproic acid has not been implicated in DI-TMA."	( Thrombotic microangiopathy associated with Valproic acid toxicity. Bohan, TP; Erikson, CL; Hebert, SA; Swinford, RD, 2017)	1.44
"Valproic acid (VPA) has shown potent anti-inflammatory effect and attenuates acute lung injury."	( Valproic acid attenuates the risk of acute respiratory failure in patients with subarachnoid hemorrhage. Chien, WC; Chu, SJ; Chung, CH; Chung, TT; Liao, WI; Tsai, SH; Wang, JC, 2018)	3.37
"Valproic acid (VPA) has anticancer activity through regulation of cell differentiation and apoptosis via inhibition of histone deacetylase (HDAC) activity and is considered a class I HDAC inhibitor."	( Inhibition of histone deacetylase 1 ameliorates renal tubulointerstitial fibrosis via modulation of inflammation and extracellular matrix gene transcription in mice. Kang, KP; Kim, D; Kim, W; Lee, S; Nguyễn-Thanh, T; Park, SK, 2018)	1.2
"Valproic acid has been shown to upregulate estrogen receptors (ERs) in breast and prostate cancer tissues."	( Magnesium valproate ameliorates type 1 diabetes and cardiomyopathy in diabetic rats through estrogen receptors. Bhadada, S; Dudhrejiya, A; Patel, B; Rabadiya, S; Vaishnav, D, 2018)	1.2
"Valproic acid (VPA) has been reported to inhibit cancer cell growth and has therapeutic use in retinal diseases. "	( Valproic Acid Inhibits Human Retinal Pigment Epithelial (hRPE) Cell Proliferation Via a P38 MAPK Signaling Mechanism. Anand, R; Del Monte, MA; Kothary, PC, 2018)	3.37
"Valproic acid (VPA) has been shown to influence the neural differentiation of NSCs through multiple signaling pathways involving glycogen synthase kinase3β (GSK3β)."	( Valproic acid promotes the neuronal differentiation of spiral ganglion neural stem cells with robust axonal growth. Lu, W; Moon, BS; Park, HJ, 2018)	2.64
"Valproic acid (VPA) has been shown to have beneficial properties in lethal hemorrhage/trauma models."	( Valproic acid improves survival and decreases resuscitation requirements in a swine model of prolonged damage control resuscitation. Alam, HB; Bhatti, UF; Biesterveld, BE; Chtraklin, K; Dennahy, IS; Graham, NJ; Kathawate, RG; Li, Y; Russo, RM; Vercruysse, CA; Williams, AM; Zhou, J, 2019)	2.68
"Valproic acid has a long-standing reputation of effectively treating the symptoms of not only epilepsy but also psychiatric conditions. "	( Valproic acid potently inhibits interictal-like epileptiform activity in prefrontal cortex pyramidal neurons. Nurowska, E; Pasierski, M; Szulczyk, B, 2019)	3.4
"Valproic acid (VPA) has been shown to regulate the levels of brain-derived neurotrophic factor (BDNF), but it is not known whether this drug can affect the neuronal responses to BDNF. "	( Downregulation of TrkB Expression and Signaling by Valproic Acid and Other Histone Deacetylase Inhibitors. Dedoni, S; Ingianni, A; Marras, L; Olianas, MC; Onali, P, 2019)	2.21
"Valproic acid (VPA) has been known to reduce neuronal injury, has anti-inflammatory and anti-apoptotic effects as a histone deacetylase (HDAC) inhibitor. "	( Effect of valproic acid on survival and neurologic outcomes in an asphyxial cardiac arrest model of rats. Jo, YH; Kang, C; Kim, J; Kim, K; Kim, MA; Lee, JH; Lee, MJ; Lee, SH; Park, CJ; Rhee, JE, 2013)	2.23
"Valproic acid (VPA) has been shown to exert anti-inflammatory and antioxidant effects in a range of diseases including septic shock. "	( Valproic acid attenuates lipopolysaccharide-induced acute lung injury in mice. Fan, YX; Gao, DP; Ji, MH; Jia, M; Li, GM; Wu, J; Yang, JJ; Zhu, SH, 2013)	3.28
"Valproic acid (VPA) has been shown to improve survival in animal models of hemorrhagic shock at a dose of 300 mg/kg. "	( Valproic acid for the treatment of hemorrhagic shock: a dose-optimization study. Alam, HB; Halaweish, I; Hwabejire, JO; Li, Y; Liu, B; Lu, J, 2014)	3.29
"Valproic acid (VPA) has been used in clinical practice as an anticonvulsant for more than four decades. "	( New perspectives of valproic acid in clinical practice. Činčárová, L; Fajkus, J; Zdráhal, Z, 2013)	2.16
"Valproic acid (VPA) has been shown to increase the reprogramming efficiency of induced pluripotent stem cells (iPSC) from somatic cells, but the mechanism by which VPA enhances iPSC induction has not been defined. "	( Valproic acid enhances Oct4 promoter activity through PI3K/Akt/mTOR pathway activated nuclear receptors. Chen, SL; Hou, DR; Kao, CH; Li, PN; Lin, CT; Lin, KH; Liu, SW; Loo, MR; Teng, HF, 2014)	3.29
"Valproic acid has demonstrated efficacy in reducing the total number of motor tics, their frequency, intensity, complexity, and impairment in a patient who had failed to respond to numerous other medications."	( Tourette disorder treated with valproic acid. Lippmann, S; Ye, L, )	1.14
"Valproic acid (VPA) has been used to treat epileptic patients because of its ability to potentiate GABA signaling in the brain. "	( Valproic acid selectively suppresses the formation of inhibitory synapses in cultured cortical neurons. Egashira, Y; Kumamaru, E; Takamori, S; Takenaka, R, 2014)	3.29
"Valproic acid (VPA) has been reported as inhibitor of histone deacetylases (HDACs). "	( Valproate ameliorates thioacetamide-induced fibrosis by hepatic stellate cell inactivation. Aher, JS; Jain, S; Jena, G; Khan, S; Tikoo, K, 2015)	1.86
"Valproic acid (VPA) has been shown to have anti-inflammatory function."	( Valproic acid alleviates memory deficits and attenuates amyloid-β deposition in transgenic mouse model of Alzheimer's disease. Chen, WL; Hong, LP; Ji, WD; Liu, JH; Long, DH; Pan, XB; Wei, P; Xuan, AG; Zhang, WJ, 2015)	2.58
"Valproic acid (VPA) has been used widely to treat mood disorder, epilepsy, and a growing number of other disorders."	( VPA alleviates neurological deficits and restores gene expression in a mouse model of Rett syndrome. Guo, W; Igarashi, K; Irie, K; Nakashima, K; Otsuka I, M; Tsujimura, K; Zhao, X, 2014)	1.12
"Valproic acid (VPA) has successfully been used in the therapy of a number of conditions including absence seizures, partial seizures, tonic-clonic seizures, bipolar disorder, schizoaffective disorder, social phobias, neuropathic pain and migraine headaches. "	( Differential ammonia decay kinetics indicates more than one concurrent etiological mechanism for symptomatic hyperammonemia caused by valproate overdose. De Oleo, RR; Mojumder, DK, )	1.57
"Valproic acid (VPA) has been widely used for the treatment of epilepsy and other neuropsychiatric diseases such as bipolar disease and major depression."	( Ciliary body toxicities of systemic oxcarbazepine and valproic acid treatments: electron microscopic study. Aktaş, Z; Cansu, A; Erdoğan, D; Göktaş, G; Kaplanoğlu, GT; Karaca, EE; Serdaroğlu, A; Seymen, CM, 2015)	1.39
"Valproic acid (VPA) has been used to treat epilepsy and bipolar disorder. "	( Valproic acid, a histone deacetylase inhibitor, regulates cell proliferation in the adult zebrafish optic tectum. Dozawa, M; Ito, Y; Kono, H; Ohshima, T; Sato, Y; Tanaka, H, 2014)	3.29
"Valproic acid (VPA) has been widely used for decades to treat epilepsy; however, its mechanism of action remains poorly understood. "	( M-current preservation contributes to anticonvulsant effects of valproic acid. Greene, DL; Hoshi, N; Kang, S; Kay, HY; Kosenko, A, 2015)	2.1
"Valproic acid (VPA) has been reported to have survival and neuroprotective effects in a cardiac arrest rat model. "	( Effect of valproic acid combined with therapeutic hypothermia on neurologic outcome in asphyxial cardiac arrest model of rats. Hwang, JE; Jo, YH; Kim, K; Kim, MA; Lee, JH; Lee, MJ, 2015)	2.26
"Valproic acid (VA) has been shown to be neuroprotective in several experimental brain diseases."	( Valproic Acid Pretreatment Reduces Brain Edema in a Rat Model of Surgical Brain Injury. Applegate, RL; Huang, L; Khatibi, NH; Krafft, P; Martin, RD; Rolland, W; Sherchan, P; Woo, W; Zhang, J, 2016)	2.6
"Valproic acid (VPA) has an extensive interindividual pharmacokinetic variability. "	( Impact of age, gender and CYP2C9/2C19 genotypes on dose-adjusted steady-state serum concentrations of valproic acid-a large-scale study based on naturalistic therapeutic drug monitoring data. Haslemo, T; Molden, E; Refsum, H; Smith, RL, 2016)	2.09
"Valproic acid (VPA) has been used to treat epileptic seizures for decades, but it may also possess therapeutic potential in other nervous system diseases. "	( Amino Acid Promoieties Alter Valproic Acid Pharmacokinetics and Enable Extended Brain Exposure. Gynther, M; Huttunen, KM; Kärkkäinen, J; Lehtonen, M; Leppänen, J; Peura, L; Rautio, J; Vernerová, M, 2016)	2.17
"• Valproic acid has a cumulative effect on inhibiting brain activity in epileptogenic regions."	( Resting-state fMRI revealed different brain activities responding to valproic acid and levetiracetam in benign epilepsy with central-temporal spikes. Dante, M; Hu, Z; Li, K; Li, Q; Li, Z; Lu, G; Wu, H; Xu, Q; Yang, F; Zhang, Q; Zhang, Z, 2017)	1.25
"Valproic acid (VPA) has been associated with coagulation factors deficiency, platelet dysfunction and hemorrhagic complications. "	( Valproic acid as an antiepileptic drug: Is there a clinical relevance for the epilepsy surgeon? Arora, A; Chandra, PS; Garg, K; Kurwale, N; Tripathi, M, 2016)	3.32
"Valproic acid has histone deacetylase (HDAC) inhibitory activity."	( Non-toxic Efficacy of the Combination of Caffeine and Valproic Acid on Human Osteosarcoma Cells In Vitro and in Orthotopic Nude-mouse Models. Hayashi, K; Hoffman, RM; Igarashi, K; Kimura, H; Miwa, S; Takeuchi, A; Tsuchiya, H; Yamamoto, N, 2016)	1.4
"Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). "	( Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1. Chen, JH; Ding, ZL; Fu, R; Gu, LZ; Hu, CP; Qin, L; Wan, YF; Wang, Y; Xu, CQ; Zheng, YL, 2017)	3.34
"Valproic acid (VPA) has been associated with hyperammonemia with and without encephalopathy. "	( Hyperammonemia following intravenous valproate loading. Beasley, MT; Cofield, S; DeWolfe, JL; Faught, E; Knowlton, RC; Limdi, NA, 2009)	1.8
"Valproic acid (VPA) has been used for many years as a drug of choice for epilepsy and mood disorders. "	( Chronic dietary administration of valproic acid protects neurons of the rat nucleus basalis magnocellularis from ibotenic acid neurotoxicity. Brignani, S; Contestabile, A; Eleuteri, S; Monti, B, 2009)	2.07
"Valproic acid also has a demonstrated efficacy in the preventive treatment of migraine with and without aura, but its tolerability profile and the possibility of serious adverse events oblige us to prescribe this neuromodulator for refractory patients."	( [The role of the neuromodulators in the preventive treatment of migraine]. Pascual-Gómez, J, )	0.85
"Valproic acid derivatives have been used for the past 10 years to control agitation in dementia, but no systematic review of the effectiveness of this treatment has been published to date."	( Valproate preparations for agitation in dementia. Lonergan, E; Luxenberg, J, 2009)	1.07
"Valproic acid (VPA) has been demonstrated to have neuroprotective effects in neurodegenerative conditions. "	( Valproic acid-mediated neuroprotection and regeneration in injured retinal ganglion cells. Biermann, J; Di Giovanni, S; Goebel, U; Grieshaber, P; Lagrèze, WA; Martin, G; Thanos, S, 2010)	3.25
"Valproic acid (VPA) has been shown to cause neural tube defects in humans and mice, but its mechanism of action has not been elucidated. "	( Ascorbic acid reverses valproic acid-induced inhibition of hoxa2 and maintains glutathione homeostasis in mouse embryos in culture. Nazarali, AJ; Wang, X; Zhang, B, 2010)	2.11
"Valproic acid has been associated with a highly variable intersubject absorptive phase; therefore, magnesium salt (magnesium valproate [MgV]) was developed to diminish variation during enteric absorption."	( A single-dose, three-period, six-sequence crossover study comparing the bioavailability of solution, suspension, and enteric-coated tablets of magnesium valproate in healthy Mexican volunteers under fasting conditions. Angeles-Moreno, AP; Contreras-Zavala, L; Marcelín-Jiménez, G; Morales-Martínez, M; Rivera-Espinosa, L, 2009)	1.8
"Valproic acid (VPA) has been used for epilepsy treatment since the 1970s. "	( Valproic acid in the complex therapy of malignant tumors. Eckschlager, T; Hrabeta, J; Hrebackova, J, 2010)	3.25
"Valproic acid (VPA) has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA) in vitro and in vivo."	( SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy. Acsadi, G; Bromberg, MB; Chan, GM; Crawford, TO; D'Anjou, G; Elsheik, B; Kissel, JT; Krosschell, KJ; LaSalle, B; Maczulski, JA; Prior, TW; Reyna, SP; Schroth, MK; Scott, CB; Simard, LR; Sorenson, SL; Swoboda, KJ, 2010)	2.02
"Valproic acid (VPA) has been reported to cause cognitive decline and parkinsonism that are reversed with cessation of medication. "	( Reversible dementia and gait disturbance after prolonged use of valproic acid. Evans, MD; Shinar, R; Yaari, R, 2011)	2.05
"Valproic acid (VPA) has been used for > 30 years in the treatment of epilepsy and is now one of the most frequently prescribed anti-epileptic drugs (AEDs) worldwide. "	( Neuroendocrine plasticity in GnRH release is disrupted by valproic acid treatment of cycling rats. Kataria, H; Kaur, G; Lakhanpal, D, 2011)	2.06
"Valproic acid (VPA) has been widely used in clinics for the treatment of multiple neuropsychiatric disorders, such as epilepsy and bipolar disorder. "	( Valproic acid induces monoamine oxidase A via Akt/forkhead box O1 activation. Shih, JC; Wu, JB, 2011)	3.25
"Valproic acid (VPA) has been used as an anticonvulsant for the treatment of epilepsy. "	( An UPLC-MS/MS method for the determination of valproic acid in blood of a fatal intoxication case. Corte-Real, F; Franco, JM; Marcos, M; Mustra, C; Pereira, AR; Proença, P; Vieira, DN, 2011)	2.07
"Valproic acid (VPA) has been suggested as a potential adjunct therapy in schizophrenia for the treatment of clinical symptoms and cognitive deficits. "	( Effects of adjunct valproic acid on clinical symptoms and saccadic eye movements in schizophrenia. Babin, SL; Larrison, AL; Patel, SS; Sereno, AB; Wassef, AA; Xing, Y, 2011)	2.14
"Valproic acid (VPA) has extensive effects on leukemic blasts through its inhibition of histone deacetylases. "	( Valproic acid triggers differentiation and apoptosis in AML1/ETO-positive leukemic cells specifically. Mejstrikova, E; Smetana, K; Starkova, J; Stary, J; Trka, J; Zapotocky, M, 2012)	3.26
"Valproic acid (VPA) has been used in clinical practice for the treatment of epilepsy and other seizure disorders and is also one of the most represented HDAC inhibitors."	( Valproic acid, a histone deacetylase inhibitor, enhances radiosensitivity in esophageal squamous cell carcinoma. Fujimura, T; Fujita, H; Fushida, S; Harada, S; Kinoshita, J; Kitagawa, H; Makino, I; Nakagawara, H; Nakamura, K; Ninomiya, I; Ohta, T; Oyama, K; Shoji, M; Tajima, H; Takamura, H, 2012)	2.54
"Valproic acid (VPA) has been used clinically as an anticonvulsant medication during pregnancy; however, it poses a neurodevelopmental risk due to its high teratogenicity. "	( Gestational valproate alters BOLD activation in response to complex social and primary sensory stimuli. Febo, M; Felix-Ortiz, AC, 2012)	1.82
"Valproic acid (VPA) has emerged as an anticancer drug via inhibition of histone deacetylases (HDACs), but the therapeutic advantages of a combination with VPA and TMZ remain poorly understood."	( Valproic acid downregulates the expression of MGMT and sensitizes temozolomide-resistant glioma cells. Hou, Y; Jeong, CH; Jeun, SS; Kim, SM; Lim, JY; Park, KY; Ryu, CH; Woo, JS; Yoon, WS, 2012)	2.54
"Valproic acid (VPA) has been used for decades in the treatment of epilepsy and psychiatric disorders, and the long-term use of VPA is regularly accompanied by hematological toxicity, including neutropenia. "	( Valproic acid treatment is associated with altered leukocyte subset development. Bartels, M; Bierings, MB; Coffer, PJ; den Breeijen, HJ; Egberts, TC; van Solinge, WW, 2012)	3.26
"Valproic acid (VPA) has a narrow therapeutic range (50-100mg/l) and exhibits nonlinear protein binding. "	( Oral/intravenous maintenance dosing of valproate following intravenous loading: a simulation. Cloyd, JC; Collins, SD; Dutta, S; Granneman, GR, 2003)	1.76
"Valproic acid has clear efficacy in the treatment of partial epilepsies. "	( The efficacy of divalproex for partial epilepsies. Smith, MC, 2003)	1.76
"Valproic acid has been used in the treatment of migraine headache for nearly 20 years. "	( Divalproex in the treatment of migraine. Freitag, FG, 2003)	1.76
"Valproic acid has been used for the past 10 years to control agitation in dementia, but no systematic review of the effectiveness of this drug has been published to date."	( Valproic acid for agitation in dementia. Cameron, M; Lonergan, ET; Luxenberg, J, 2004)	2.49
"Valproic acid (VPA) has been shown to inhibit histone deacetylase activity and to synergize with all-trans retinoic acid (ATRA) in the differentiation induction of acute myelogenous leukemia (AML) blasts in vitro. "	( Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid. Aivado, M; Bernhardt, A; Gattermann, N; Germing, U; Haas, R; Hildebrandt, B; Kuendgen, A; Strupp, C, 2004)	2.03
"Valproic acid (VPA), which has demonstrated efficacy in the treatment of bipolar disorder, has been shown to alter components of the phosphoinositide (PI) signaling cascade and to increase gene expression mediated by the transcription factor activator protein 1 (AP-1). "	( Effect of valproic acid on serotonin-2A receptor signaling in C6 glioma cells. Burke, T; Hensler, JG; Javors, M; Siafaka-Kapadai, A; Sullivan, NR, 2004)	2.17
"Valproic acid (VPA) has the potential to benefit patients suffering from human immunodeficiency virus (HIV)-associated cognitive impairment. "	( Effects of valproic acid coadministration on plasma efavirenz and lopinavir concentrations in human immunodeficiency virus-infected adults. Cruttenden, K; DiCenzo, R; Gelbard, H; Morse, G; Peterson, D; Riggs, G; Schifitto, G, 2004)	2.16
"Valproic acid has been used as one of the primary anticonvulsants for generalized seizures in children for the past 25 years."	( Valproic acid-induced pancreatitis in childhood epilepsy: case series and review. Berg, M; Breault, R; Sinclair, DB, 2004)	2.49
"Valproic acid (VPA) has long been used as an antiepileptic drug and recently as a mood stabilizer, and evidence is increasing that VPA exerts neuroprotective effects through changes in a variety of intracellular signalling pathways including upregulation of Bcl-2 protein with an antiapoptotic property and inhibiting glycogen synthase kinase 3-beta, which is considered to promote cell survival. "	( Benefit of valproic acid in suppressing disease progression of ALS model mice. Goto, M; Hamasaki, T; Miyaguchi, K; Sakoda, S; Sugai, F; Sumi, H; Yamamoto, Y; Zhou, Z, 2004)	2.16
"Valproic acid (VPA), which has long been used in the treatment of epilepsy, was shown recently to be an effective histone deacetylase inhibitor that can induce differentiation of neoplastically transformed cells."	( Valproic acid, in combination with all-trans retinoic acid and 5-aza-2'-deoxycytidine, restores expression of silenced RARbeta2 in breast cancer cells. Gudas, LJ; Mongan, NP, 2005)	2.49
"Valproic acid has been previously associated with hematologic toxicity, including a reversible myelodysplasia-like syndrome without chromosomal abnormalities. "	( Acute leukemia associated with valproic acid treatment: a novel mechanism for leukemogenesis? Bair, AK; Coyle, TE; Mehdi, S; Stein, C; Vajpayee, N; Wright, J, 2005)	2.06
"Valproic acid has been used to treat mania and bipolar disorder, but its mechanism of action is not agreed on. "	( Microarray analysis of rat brain gene expression after chronic administration of sodium valproate. Bell, JM; Bosetti, F; Manickam, P, 2005)	1.77
"Valproic acid (VPA) has been demonstrated to be able to inhibit histone deacetylase activity and to synergize with all-trans retinoic acid (ATRA) in inducing the differentiation of acute myeloid leukemia (AML) cells. "	( Valproic acid and all-trans retinoic acid for the treatment of elderly patients with acute myeloid leukemia. Chaibi, P; Degos, L; Dombret, H; Raffoux, E, 2005)	3.21
"Valproic acid (VPA) has been used as an anticonvulsant agent for the treatment of epilepsy, as well as a mood stabilizer for the treatment of bipolar disorder, for several decades. "	( Induction of osteogenic differentiation of human mesenchymal stem cells by histone deacetylase inhibitors. Bae, YC; Cho, HH; Jung, JS; Kim, YJ; Park, HT; Suh, KT, 2005)	1.77
"Valproic acid has been widely used for the treatment of epilepsy. "	( [Hyperammonemia secondary to the use of valproic acid: case report]. Fernandes, RM; Funayama, CA; Turcato, Mde F; Wichert-Ana, L, 2005)	2.04
"Valproic acid (VPA) has been used for the treatment of epilepsy and bipolar disorders for more than 30 yr. "	( Suppression of adiponectin gene expression by histone deacetylase inhibitor valproic acid. Qiao, L; Schaack, J; Shao, J, 2006)	2.01
"Valproic acid (VPA) has long been known to cause spina bifida, a neural tube defect, and other effects in fetuses of women treated with this drug. "	( Mode of action: inhibition of histone deacetylase, altering WNT-dependent gene expression, and regulation of beta-catenin--developmental effects of valproic acid. Wiltse, J, )	1.77
"Valproic acid has been demonstrated to mediate cytotoxic effects against tumor cells by acting as a histone-deacetylase inhibitor. "	( Synergistic effects of valproic acid and mitomycin C in adenocarcinoma cell lines and fresh tumor cells of patients with colon cancer. Atmaca, A; Chow, KU; Friedmann, I; Jäger, E; Weidmann, E, 2006)	2.09
"Valproic acid (VPA), which has a wide range of therapeutic applications, is known as a potent teratogen that induces neural tube defects in vertebrates. "	( A novel embryotoxic estimation method of VPA using ES cells differentiation system. Fujiwara, Y; Hiroyama, M; Murabe, M; Sanbe, A; Tanoue, A; Yamauchi, J, 2007)	1.78
"Valproic acid (VPA) has been used as anticonvulsants, however, it induces hepatotoxicity such as microvesicular steatosis and necrosis in the liver. "	( Gene expression profiles of murine fatty liver induced by the administration of valproic acid. Chung, H; Hong, I; Kang, KS; Kim, HL; Kim, JH; Kim, M; Kong, G; Lee, BH; Lee, MH; Lee, MO; Yoon, BI, 2007)	2.01
"Valproic acid (VPA) has been used as an anticonvulsant for decades. "	( Valproic acid for the treatment of myeloid malignancies. Gattermann, N; Kuendgen, A, 2007)	3.23
"Valproic acid (VPA) has been recently investigated for its anticancer properties in different tumors, including malignant gliomas. "	( Valproic acid increases the in vitro effects of nitrosureas on human glioma cell lines. Balzarotti, M; Boiardi, A; Calatozzolo, C; Ciusani, E; Croci, D; de Grazia, U; Salmaggi, A, 2007)	3.23
"Valproic acid has not been shown to be superior to comparator drugs and was inferior to prochlorperazine in one trial."	( Use of intravenous valproic acid for acute migraine. Foraker, KC; Frazee, LA, 2008)	1.4
"Valproic acid has recently been shown to be associated with liver disease in man. "	( Hepatotoxicity of sodium valproate and other anticonvulsants in rat hepatocyte cultures. Kingsley, E; Tolman, KG; Tweedale, R, 1980)	1.7
"Valproic acid monotherapy has demonstrated efficacy equivalent to that of carbamazepine, phenytoin, and phenobarbital in the treatment of both generalised and partial seizures and ethosuximide in the treatment of absence seizures."	( Valproic acid. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy. Davis, R; McTavish, D; Peters, DH, 1994)	2.45
"Valproic acid has a wider antiepileptic spectrum than any other antiepileptic drug (AED) in clinical use. "	( [Sodium valproate--current status of pharmacological research]. Chapman, AG, 1994)	1.73
"Valproic acid has been proven to be efficient in the treatment of bipolar affective disorders as an adjunctive agent to lithium and carbamazepine. "	( Valproic acid in ultra-rapid cycling: a case report. Dannon, P; Iancu, I; Kotler, M; Lepkifker, E; Ziv, R, 1995)	3.18
"Valproic acid has been shown to be effective in migraine prophylaxis. "	( High-dose versus low-dose valproic acid as a prophylactic medication. Goldstein, J; Taylor, K, 1996)	2.04
"Valproic acid (VA) has been reported to be effective in status epilepticus (SE) when given rectally. "	( The role of intravenous valproic acid in status epilepticus. Yamamoto, LG; Yim, GK, 2000)	2.06
"Valproic acid (VPA) has been considered as a possible treatment agent for malignant gliomas. "	( Different effects of valproic acid on proliferation and migration of malignant glioma cells in vitro. Hernaíz Driever, P; Keller, E; Knüpfer, H; Knüpfer, MM; Pulzer, F; Schindler, I, )	1.89
"Valproic acid (VPA) has been shown to induce growth-arrest and differentiation of human neuroectodermal tumors similarly to several other fatty acids. "	( Induction of differentiation and suppression of malignant phenotype of human neuroblastoma BE(2)-C cells by valproic acid: enhancement by combination with interferon-alpha. Blaheta, R; Cinatl, J; Driever, PH; Kotchetkov, R; Vogel, JU, 2002)	1.97
"Valproic acid has become a regular component of antiepileptic therapy. "	( [Valproic acid in the treatment of epilepsy with special emphasis on serum level determination (author's transl)]. Fröscher, W; Gugler, R; Schulz, HU, 1978)	2.61
"Valproic acid has previously been demonstrated to decrease the secretion of multiple pituitary hormones; however, clinical symptoms associated with decreased hormone secretion have not been described. "	( Pubertal arrest associated with valproic acid therapy. Bale, JF; Cook, JS; Hoffman, RP, )	1.86
"Valproic acid has been implicated in at least 100 cases of fatal acute liver failure. "	( Incidental microvesicular steatosis due to valproic acid anticonvulsant therapy. Bacon, BR; Gholson, CF; Gonzalez, E; Netchvolodoff, CV; Ray, M; Scott, DA, 1991)	1.99
"Valproic acid (VPA) has been postulated to exert its anticonvulsant effects by interaction with the postsynaptic GABA receptor. "	( Effects of valproic acid in cultured mammalian neurons. Buchhalter, JR; Dichter, MA, 1986)	2.1
"Valproic acid has probable teratogenic potential in humans but the number of reported cases is few and the spectrum of anomalies is broad so it is not possible to delineate a definite fetal valproate syndrome."	( Congenital malformations associated with maternal use of valproic acid. Gauthier, M; Huot, C; Larbrisseau, A; Lebel, M, 1987)	1.24

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Valproic acid could suppress invasiveness of prostate cancer cell lines PC3 and Du145. It can increase lipoprotein(a) and decrease fibrinogen, which may increase the risk of stroke or other thrombotic events.

Excerpt	Reference	Relevance
"Valproic acid may inhibit cisplatin-induced kidney injury by suppressing apoptosis, inflammatory responses, and glomerular damage throughout the kidneys by suppressing proximal tubular cell damage."	( Valproic acid treatment attenuates cisplatin-induced kidney injury by suppressing proximal tubular cell damage. Aizawa, F; Goda, M; Hamano, H; Ishizawa, K; Itobayashi, S; Izawa-Ishizawa, Y; Kanda, M; Miyata, K; Niimura, T; Sakurada, T; Sugimoto, Y; Yagi, K; Yoshioka, T; Zamami, Y, 2023)	3.07
"Valproic acid could suppress invasiveness of prostate cancer cell lines PC3 and Du145, possibly through multiple pathways other than the SAMD4 pathway. "	( Role of SMAD4 in the mechanism of valproic acid's inhibitory effect on prostate cancer cell invasiveness. Huang, Z; Jiang, W; Jin, X; Wang, M; Wang, Z; Xia, Q; Zhang, Y; Zheng, Y, 2014)	2.12
"Valproic acid does not increase the percentage of porcine-rhesus monkey iSCNT embryos that reach the blastocyst stage."	( Production of rhesus monkey cloned embryos expressing monomeric red fluorescent protein by interspecies somatic cell nuclear transfer. Gao, QS; Guo, Q; Hong, Y; Jin, JX; Jin, L; Kang, JD; Li, S; Yan, CG; Yin, XJ; Zhu, HY, 2014)	1.12
"Valproic acid does not increase radioiodine uptake and does not have anticancer activity in patients with advanced, radioiodine-negative thyroid cancer of follicular cell origin."	( A phase II trial of valproic acid in patients with advanced, radioiodine-resistant thyroid cancers of follicular cell origin. Kebebew, E; Merkel, R; Neychev, V; Nilubol, N; Patel, D; Reynolds, JC; Sadowski, SM; Yang, L, 2017)	2.22
"Valproic acid did not increase PTX-induced α-tubulin acetylation."	( Valproic Acid as a Promising Co-Treatment With Paclitaxel and Doxorubicin in Different Ovarian Carcinoma Cell Lines. Fiedor, E; Gregoraszczuk, EL; Grzyb, E; Kwiecińska, P; Ptak, A; Taubøll, E, 2016)	2.6
"Valproic acid can increase lipoprotein(a) and decrease fibrinogen, which may increase the risk of stroke or other thrombotic events."	( Thrombophilic risk factors in epileptic children treated with valproic Acid. Akar, N; Deda, G; Ertem, M; Teber, S; Unal, O, 2009)	1.31
"Valproic acid can inhibit the growth of HL-60/HT cells and enhance their Ara-C sensitivity possibly by increasing P27(Kip1) expression and causing cell cycle arrest in G(1) phase."	( [Effect of valproic acid on the expression of P27(Kip1) and P170 and drug resistance of HL-60/HT cells]. Li, YQ; Ma, LP; Nie, DN; Wang, XJ; Wu, YD; Xie, SF; Yin, SM, 2009)	1.46
"Valproic acid is a rare cause of eosinophilic pleural effusion."	( [Eosinophilic pleural effusion related to taking valproic acid]. Bally, C; Burgel, PR; Dusser, D; Kanaan, R; Kraoua, S; Lacronique, J; Martin, C, 2011)	1.34
"Valproic acid is thought to increase renal metabolism of glutamate and may contribute to ammonia production."	( Levocarnitine for valproic-acid-induced hyperammonemic encephalopathy. Mock, CM; Schwetschenau, KH, 2012)	1.1
"Valproic acid increased the lower oesophageal sphincter pressure by 41% (14.0 +/- 2.1 mmHg vs. "	( Effect of non-selective gamma-aminobutyric acid receptor stimulation on motor function of the lower oesophageal sphincter and gastro-oesophageal reflux in healthy human subjects. Allocca, M; Cantù, P; Carmagnola, S; Penagini, R; Savojardo, D, 2003)	1.76
"Valproic acid may increase SMN levels both by activating the SMN promoter and by preventing exon 7 skipping in SMN transcripts."	( Valproic acid increases SMN levels in spinal muscular atrophy patient cells. Burghes, AH; Chen, X; Coovert, DD; Fischbeck, KH; Hill, B; Huynh, TN; Jarecki, J; Markowitz, JA; Perhac, JS; Schussler, K; Sumner, CJ; Taylor, JP, 2003)	2.48
"Valproic acid (VPA) may increase surgical bleeding. "	( Is operative blood loss associated with valproic acid? Analysis of bilateral femoral osteotomy in children with total involvement cerebral palsy. Carney, BT; Minter, CL, )	1.84
"Valproic acid caused an increase in neural tube defects, ibuprofen increased the incidence of abnormal maxillary processes, and diphenhydramine increased the number of embryos with distorted body morphology."	( Evaluation of the rat embryo culture system as a predictive test for human teratogens. Buttar, HS; Guest, I; Smith, S; Varma, DR, 1994)	1.01
"Valproic acid (VPA) may cause impaired platelet function, thrombocytopenia and, occasionally, severe bleeding. "	( Valproate-mediated disturbances of hemostasis: relationship to dose and plasma concentration. Collins, M; Gidal, B; Jones, J; Maly, M; Pitterle, M; Spencer, N; Williams, E, 1994)	1.73
"Valproic acid may increase the hepatotoxicity of phenytoin."	( Increased microsomal irreversible binding of phenytoin by valproic acid. Huang, JD; Lai, ML; Wang, SL, 1991)	1.25
"Valproic acid is known to cause an increase in blood ammonia levels in humans at the usual clinical dose. "	( Salicylate potentiates valproate-induced hyperammonemia in the rat. Uetrecht, JP, 1987)	1.72
"Valproic acid may cause a characteristic pattern of minor facial malformations."	( Teratogen update: valproic acid. Lammer, EJ; Oakley, GP; Sever, LE, 1987)	1.33
"Valproic acid did not inhibit the fatty acyl-CoA oxidase nor the cyanide-insensitive acyl-CoA oxidation."	( The inhibition by valproic acid of the mitochondrial oxidation of monocarboxylic and omega-hydroxymonocarboxylic acids: possible implications for the metabolism of gamma-aminobutyric acid. Draye, JP; Vamecq, J, 1987)	1.33

Treatment

Valproic acid (VPA) treatment during pregnancy is a risk factor for developing autism spectrum disorder, cognitive deficits, and stress-related disorders. Treatment with primidone reduced free-C levels in LE/LY in NPC1-null/mutant cells. Valproic Acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine.

Excerpt	Reference	Relevance
"Valproic acid-treated animals demonstrated significantly better neuroseverity scores on postinjury 1 (control, 9.2 ± 4.4; VPA, 0 ± 0; p = 0.001)."	( A single dose of valproic acid improves neurologic recovery and decreases brain lesion size in swine subjected to an isolated traumatic brain injury. Alam, HB; Biesterveld, BE; Chtraklin, K; Kemp, MT; O'Connell, RL; Pai, MP; Rajanayake, KK; Vercruysse, CA; Wakam, GK, 2021)	1.68
"Valproic acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine."	( The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy. Bax, HI; Burger, D; Colbers, A; Crespo, R; de Mendonça Melo, M; de Vries-Sluijs, TEMS; Gruters, RA; Hossain, T; Kan, TW; Katsikis, PD; Koch, BCP; Li, L; Lungu, C; Mahmoudi, T; Mesplède, T; Mueller, YM; Nouwen, JL; Overmars, RJ; Palstra, RJ; Papageorgiou, G; Prins, HAB; Rao, S; Rijnders, BJA; Rokx, C; Schurink, CAM; Stoszko, M; van de Vijver, DAMC; van Gorp, ECM; van Kampen, JJA; van Nood, E; Verbon, A, 2023)	1.63
"Valproic acid (VPA) treatment during pregnancy is a risk factor for developing autism spectrum disorder, cognitive deficits, and stress-related disorders in children. "	( Adolescent swimming exercise following maternal valproic acid treatment improves cognition and reduces stress-related symptoms in offspring mice: Role of sex and brain cytokines. Amouzad Mahdirejei, H; Barzegari, A; Esmaeili, MH; Hanani, M; Salari, AA, 2023)	2.61
"Valproic acid-treated animals had significantly less neurologic impairment on days 2 (16.3 ± 2.0 vs."	( Prolonging the therapeutic window for valproic acid treatment in a swine model of traumatic brain injury and hemorrhagic shock. Alam, HB; Chtraklin, K; Dimonte, D; Ho, JW; Jin, G; Joaquin, TA; Keeney-Bonthrone, TP; Latif, Z; Ober, RA; Pai, MP; Vercruysse, C; Wen, B, 2023)	1.9
"Valproic acid treatment showed higher gene expression of neuron-specific enolase promoter than without treatment."	( Combined Method of Neuronal Cell-Inducible Vector and Valproic Acid for Enhanced Gene Expression under Hypoxic Conditions. Baek, D; Cheong, E; Ha, Y; Kim, J; Lee, D; Oh, J; Yun, Y, 2020)	1.53
"Valproic acid-treated animals demonstrated significantly less neurologic impairment on PID 1 and returned to baseline faster (PID 1 mean neurologic severity score, control = 22 ± 3 vs."	( Administration of valproic acid in clinically approved dose improves neurologic recovery and decreases brain lesion size in swine subjected to hemorrhagic shock and traumatic brain injury. Alam, HB; Bhatti, UF; Biesterveld, BE; Chtraklin, K; Kemp, MT; O'Connell, RL; Pai, MP; Siddiqui, AZ; Srinivasan, A; Vercruysse, CA; Wakam, GK; Williams, AM, 2021)	1.68
"Like valproic acid, treatment with primidone reduced free-C levels in LE/LY in NPC1-null/mutant cells."	( Beneficial effects of primidone in Niemann-Pick disease type C (NPC)-model cells and mice: Reduction of unesterified cholesterol levels in cells and extension of lifespan in mice. Ashikawa, H; Honda, T; Mogi, H; Murayama, T; Nakamura, H, 2021)	1.08
"Valproic acid (VPA) treatment is associated with autism spectrum disorder in humans, and ferrets can be used as a model to test this; so far, it is not known whether ferrets react to developmental VPA exposure with gyrencephalic abnormalities. "	( Neonatal valproic acid exposure produces altered gyrification related to increased parvalbumin-immunopositive neuron density with thickened sulcal floors. Aoki, I; Kamiya, S; Sawada, K, 2021)	2.48
"Valproic acid (VPA) treatment improves survival in animal models of injuries on doses higher than those allowed by Food and Drug Administration (FDA). "	( Assessment of the Cytoprotective Effects of High-Dose Valproic Acid Compared to a Clinically Used Lower Dose. Alam, HB; Bhatti, UF; Biesterveld, BE; Kemp, M; Li, Y; Liu, B; Remmer, H; Russo, R; Tagett, R; Wakam, G; Williams, AM, 2021)	2.31
"As valproic acid (VPA) treatment has been shown to improve survival in animal models of lethal trauma, we hypothesized that it would also attenuate the degree of acute kidney injury."	( Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma. Alam, HB; Biesterveld, BE; Kemp, MT; O'Connell, RL; Remmer, H; Shamshad, A; Siddiqui, AZ; Smith, WM; Wakam, GK; Williams, AM, 2021)	2.58
"Valproic acid-treated animals demonstrated significantly less neurologic impairment between PID 1 to 5 and smaller brain lesions on PID 3 (mean lesion size ± SEM, mm: ISCS = 4,956 ± 1,511 versus ISCS + VPA = 828 ± 279; p = 0.047)."	( Valproic acid decreases brain lesion size and improves neurologic recovery in swine subjected to traumatic brain injury, hemorrhagic shock, and polytrauma. Alam, HB; Chtraklin, K; Dennahy, IS; Eidy, H; Georgoff, PE; Ghandour, MH; Han, Y; Li, Y; Nikolian, VC; Pai, MP; Srinivasan, A, 2017)	2.62
"Valproic acid treatment marginally enhanced global DNA methylation in the frontal cortex."	( Brain derived neurotrophic factor expression and DNA methylation in response to subchronic valproic acid and/or aldosterone treatment. Balagova, L; Buzgoova, K; Graban, J; Hlavacova, N; Jezova, D, 2019)	1.46
"Valproic acid treatment of human dermal papilla cells led to increased β-catenin levels and nuclear accumulation and inhibition of GSK-3β by phosphorylation."	( Valproic acid promotes human hair growth in in vitro culture model. Choi, SJ; Eun, HC; Jo, SJ; Kim, KH; Kwon, O; Lee, JY; Park, PJ; Park, WS; Yoon, SY, 2013)	2.55
"Valproic acid treatment decreased baseline levels of dopamine and also attenuated the excess dopamine release in response to the CS in the amygdala of methamphetamine-sensitized rats."	( Valproic acid inhibits excess dopamine release in response to a fear-conditioned stimulus in the basolateral complex of the amygdala of methamphetamine-sensitized rats. Inada, K; Ishigooka, J; Kasai, A; Miyagi, J; Oshibuchi, H, 2014)	2.57
"Valproic acid treatment lowers plasma PAI-1 antigen levels and changes the fibrinolytic balance measured as t-PA/PAI-1 ratio in a profibrinolytic direction. "	( Profibrinolytic effect of the epigenetic modifier valproic acid in man. Bergh, N; Hrafnkelsdóttir, TJ; Jern, S; Larsson, P; Ridderstråle, W; Saluveer, O, 2014)	2.1
"Valproic acid pretreatment decreased the duration of CSD-induced freezing episodes and reversed the CSD-induced reduction in locomotor activity."	( The thalamic reticular nucleus is activated by cortical spreading depression in freely moving rats: prevention by acute valproate administration. Akcali, D; Bolay, H; Charles, A; Dilekoz, E; Filiz, A; Sara, Y; Tepe, N, 2015)	1.14
"Valproic acid treated animals were treated from 5 days preceding behavioral testing in the Morris water maze at a clinically relevant concentration."	( Standard dose valproic acid does not cause additional cognitive impact in a rodent model of intractable epilepsy. Jellett, AP; Jenks, K; Lucas, M; Scott, RC, 2015)	1.5
"Valproic acid (VPA) treatment protected hippocampal neurons from radiation-induced damage in both cell culture and animal models."	( Valproic acid enhances the efficacy of radiation therapy by protecting normal hippocampal neurons and sensitizing malignant glioblastoma cells. DeWees, TA; Engelbach, JA; Garbow, JR; Hallahan, AN; Hallahan, DE; Karvas, RM; Laszlo, A; Thotala, D, 2015)	2.58
"Valproic acid (VPA) treatment was applied during the culture of parthenogenetic embryos. "	( Valproic Acid Improves Porcine Parthenogenetic Embryo Development Through Transient Remodeling of Histone Modifiers. Huang, Y; Li, T; Li, Z; Ouyang, H; Pang, D; Wang, A; Wang, B; Yuan, L, 2015)	3.3
"Mean valproic acid treatment duration was 2.80±1.96 years."	( Duration of valproic acid monotherapy correlates with subclinical thyroid dysfunction in children with epilepsy. Bogićević, D; Ilić, V; Ješić, M; Kovačević, M; Kovačević, SV; Miljković, B; Prostran, M, 2016)	1.27
"Valproic acid treatment similarly increased the GM3 level and reduced phosphorylation of EGFR in U87MG glioma cells and inhibited their proliferation."	( Induction of Glycosphingolipid GM3 Expression by Valproic Acid Suppresses Cancer Cell Growth. Kawashima, N; Nakayama, KI; Nishimiya, Y; Takahata, S, 2016)	1.41
"Valproic acid-treated animals developed biochemical evidence of FS as judged by elevated serum gamma-glutamyl transferase (γ-GT), alkaline phosphatase (ALP), creatinine (Cr), and blood urea nitrogen (BUN) along with hypokalaemia, hypophosphataemia, and a decrease in serum uric acid. "	( Mechanism of valproic acid-induced Fanconi syndrome involves mitochondrial dysfunction and oxidative stress in rat kidney. Heidari, R; Jafari, F; Khodaei, F; Niknahad, H; Shirazi Yeganeh, B, 2018)	2.29
"Valproic acid (VPA) treatment and paraoxonase1/arylesterase (PON1/Aryl) activities are related to the production of free radicals. "	( Early effects of sodium valproate monotherapy on serum paraoxonase/arylesterase activities. Bartzeliotou, A; Fytou-Pallikari, A; Giannoulia-Karantana, A; Karikas, GA; Papaevangelou, V; Papassotiriou, I; Regoutas, S; Schulpis, KH; Thanopoulou, C, 2009)	1.8
"Valproic acid treatment did not affect inflammation parameters; however, valproic acid treatment resulted in reduced epithelial thickness as compared to vehicle treated mice (p < 0.01), reduced subepithelial collagen deposition (p < 0.05) and attenuated airway hyperresponsiveness (p < 0.05 and p < 0.01 for the two highest doses of methacholine, respectively)."	( Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease. Dang, W; De Sampayo, N; El-Osta, A; Karagiannis, TC; Royce, SG; Tang, ML; Ververis, K, 2011)	1.41
"Valproic acid treatment also increased the immunofluorescent signal for H3K9ac in SCNT embryos in a pattern similar to that of in vitro fertilized (IVF) embryos."	( Valproic acid improves the in vitro development competence of bovine somatic cell nuclear transfer embryos. Li, Y; Su, J; Wang, L; Wang, Y; Xiong, X; Xu, W; Zhang, Y, 2012)	2.54
"Valproic acid (VPA) treatment in female patients is suggested to be associated with the occurrence of a variety of endocrine side effects that include many characteristic symptoms of polycystic ovary syndrome (PCOS). "	( Valproic acid fails to induce polycystic ovary syndrome in female rats. Lagace, DC; Nachtigal, MW, 2003)	3.2
"Valproic acid treatment caused a marked inhibition of histone deacetylases activity."	( Expressional changes after histone deacetylase inhibition by valproic acid in LNCaP human prostate cancer cells. Hemmerlein, B; Ringert, RH; Schweyer, S; Seseke, F; Thelen, P; Wuttke, W, 2004)	1.29
"Valproic acid treatment, administered at 600 microg/h for 2 weeks via s.c."	( Valproic Acid prolongs survival time of severe combined immunodeficient mice bearing intracerebellar orthotopic medulloblastoma xenografts. Adesina, A; Antalffy, B; Blaney, SM; Lau, CC; Li, XN; Ou, CN; Pietsch, T; Shu, Q; Su, JM, 2006)	2.5
"Valproic acid treatment of these xenografts showed potent in vivo anti-medulloblastoma activity."	( Valproic Acid prolongs survival time of severe combined immunodeficient mice bearing intracerebellar orthotopic medulloblastoma xenografts. Adesina, A; Antalffy, B; Blaney, SM; Lau, CC; Li, XN; Ou, CN; Pietsch, T; Shu, Q; Su, JM, 2006)	2.5
"Valproic acid treatment may modulate the insulin/IGF-1 growth factor signaling pathway, because VA promoted dauer larvae formation and DAF-16 nuclear localization."	( Valproic acid extends Caenorhabditis elegans lifespan. Collins, JJ; Evason, K; Huang, C; Hughes, S; Kornfeld, K, 2008)	2.51
"Valproic acid treatment, although also associated with hyperhomocysteinaemia, only shows a lowering effect on vitamin B6 levels, which seems to be independent of the MTHFR genotype."	( Anti-epileptic drug treatment in children: hyperhomocysteinaemia, B-vitamins and the 677C-->T mutation of the methylenetetrahydrofolate reductase gene. Artuch, R; Cardo, E; Colomé, C; Farré, C; Monrós, E; Pineda, M; Valls, C; Vilaseca, MA, 2000)	1.03
"Valproic acid treatment resulted in a significantly higher retention of 65Zn in maternal liver and lower amounts in uterus, placenta and embryos than in controls."	( The effect of valproic acid on 65Zn distribution in the pregnant rat. Hurley, LS; Keen, CL; Peters, JM, 1989)	1.36
"Treatment with valproic acid (VPA) improves outcomes in models of severe TBI with concurrent hemorrhage."	( A single dose of valproic acid improves neurologic recovery and decreases brain lesion size in swine subjected to an isolated traumatic brain injury. Alam, HB; Biesterveld, BE; Chtraklin, K; Kemp, MT; O'Connell, RL; Pai, MP; Rajanayake, KK; Vercruysse, CA; Wakam, GK, 2021)	1.3
"Treatment with valproic acid (VPA) deteriorates hippocampal neurogenesis, which leads to memory impairment. "	( Hesperidin Reduces Memory Impairment Associated with Adult Rat Hippocampal Neurogenesis Triggered by Valproic Acid. Anosri, T; Aranarochana, A; Kaewngam, S; Pannangrong, W; Sirichoat, A; Welbat, JU; Wigmore, P, 2021)	1.19
"Cell treatment with Valproic Acid reduced cell proliferation and induced G0/G1 cell cycle arrest in MCF-7 and G2/M block in MDA-MB-231 cells. "	( Valproic acid inhibits cell growth in both MCF-7 and MDA-MB231 cells by triggering different responses in a cell type-specific manner. De Amicis, F; Forastiero, M; Giordano, F; Marrelli, M; Marsico, S; Mauro, L; Naimo, GD; Panno, ML; Paolì, A, 2023)	2.68
"Treatment with valproic acid for bipolar disorder resulted in complete resolution of symptoms."	( A Case of Recurrent Hypersomnia With Autonomic Dysfunction. Friedman, D; Kothare, SV; Mahmoudi, M; Vendrame, M, 2017)	0.79
"Treatment with valproic acid did not modify BDNF gene expression in the hippocampus but reduced BDNF mRNA levels in the brain cortex. "	( Brain derived neurotrophic factor expression and DNA methylation in response to subchronic valproic acid and/or aldosterone treatment. Balagova, L; Buzgoova, K; Graban, J; Hlavacova, N; Jezova, D, 2019)	1.09
"Treatment with valproic acid, a histone deacetylase inhibitor (HDACi), attenuated mutant ataxin-3-induced cell toxicity and suppression of acetyl histone H3, phosphorylated cAMP-responsive element binding protein (p-CREB) as well as c-Fos expression."	( Valproic acid attenuates the suppression of acetyl histone H3 and CREB activity in an inducible cell model of Machado-Joseph disease. Chen, DB; Feng, L; Li, XH; Liang, XL; Lin, XP; Pan, SY; Pei, Z; Xie, CG; Xie, QY, 2014)	2.18
"Treatment with valproic acid led to increases in weight/BMI and decreases in total red blood cells (RBC), hemoglobin, and hematocrit."	( Placebo-controlled trial of valproic Acid versus risperidone in children 3-7 years of age with bipolar I disorder. Altaye, M; Delgado, S; Kowatch, RA; Lagory, D; Monroe, E; Scheffer, RE, 2015)	1.05
"A treatment with valproic acid was started, obtaining control of the neurological disease."	( Recurrent seizures during acute acquired toxoplasmosis in an immunocompetent traveller returning from Africa. Bassetti, M; Beltrame, A; Buonfrate, D; Crichiutti, G; Meroni, V; Venturini, S, 2016)	0.76
"Treatment with valproic acid decreases muscle myostatin levels and enhances both follistatin expression and the inactivating phosphorylation of GSK-3beta, while these parameters are not affected by trichostatin-A."	( Deacetylase inhibitors modulate the myostatin/follistatin axis without improving cachexia in tumor-bearing mice. Baccino, FM; Bonelli, G; Bonetto, A; Costelli, P; Minero, VG; Penna, F; Reffo, P, 2009)	0.69
"Treatment with valproic acid (VPA) has been shown to up-regulate various survival pathways and improve outcome."	( Identification of a novel potential biomarker in a model of hemorrhagic shock and valproic acid treatment. Alam, HB; deMoya, M; Dillon, ST; Fukudome, EY; Kheirbek, T; Li, Y; Libermann, TA; Liu, B; Sailhamer, EA; Velmahos, G, 2010)	0.93
"Treatment with valproic acid was able to increase the percentage of PTEN-positive cultures up to 80 and 74% for PTEN protein and mRNA determination, respectively."	( Epigenetic modulation of PTEN expression during antiandrogenic therapies in human prostate cancer. Biordi, L; Festuccia, C; Ficorella, C; Flati, V; Gravina, GL; Martella, F; Ricevuto, E; Tombolini, V, 2009)	0.69
"Treatment with valproic acid induced extensive changes in gene expression in the axon guidance pathway."	( Epigenetic modification of vomeronasal (V2r) precursor neurons by histone deacetylation. Broad, KD; Emson, PC; Keverne, EB; Xia, J, 2010)	0.7
"Treatment with valproic acid, an HDAC inhibitor, could significantly increase the expression of Oct4 in C-33A cells, but only slightly increased Oct4 in CaSki cells."	( HDAC1/DNMT3A-containing complex is associated with suppression of Oct4 in cervical cancer cells. Gong, W; He, F; Huang, G; Liu, D; Zhang, L; Zheng, Y; Zhou, P, 2012)	0.72
"Treatment with valproic acid (VPA), a histone deacetylase inhibitor, at 3 dosing regimens (300mg/kg at D2-9PP; 100mg/kg at D2-4PP, 200mg/kg at D5-7PP, 300mg/kg at D8-9PP; 100mg/kg at D2-5PP, 200mg/kg at D6-9PP) prior to daily separation reversed such a decrease in fear-potentiated startle."	( Neonatal isolation decreases cued fear conditioning and frontal cortical histone 3 lysine 9 methylation in adult female rats. Chen, LH; Cheng, LY; Cherng, CG; Kao, GS; Su, CC; Tzeng, WY; Wang, CY; Yu, L, 2012)	0.72
"Treatment with valproic acid 1000 mg as a continuous intravenous infusion over 24 hours was initiated."	( Acute seizures due to a probable interaction between valproic acid and meropenem. Borrás-Blasco, J; Coves-Orts, FJ; Murcia-López, A; Navarro-Ruiz, A; Palacios-Ortega, F, 2005)	0.92
"When treatment with valproic acid is the most appropriate treatment to achieve optimal seizure control, a number of measures can be implemented to minimise risk to the fetus."	( Valproic acid in epilepsy : pregnancy-related issues. Genton, P; Semah, F; Trinka, E, 2006)	2.09
"Treatment with valproic acid prolonged survival time in two (D283-MED and MHH-MED-1) of the three models and was associated with induction of histone hyperacetylation, inhibition of proliferation and angiogenesis, and enhancement of apoptosis and differentiation."	( Valproic Acid prolongs survival time of severe combined immunodeficient mice bearing intracerebellar orthotopic medulloblastoma xenografts. Adesina, A; Antalffy, B; Blaney, SM; Lau, CC; Li, XN; Ou, CN; Pietsch, T; Shu, Q; Su, JM, 2006)	2.12
"Treatment with valproic acid decreased the complaints."	( Autonomic headache with autonomic seizures: a case report. Kaleagasi, H; Ozge, A; Yalçin Tasmertek, F, 2006)	0.67
"Treatment with valproic acid resulted in a rise of GABA-concentration in cerebrospinal fluid but did not ameliorate clinical symptoms."	( [Development of brain atrophy, therapy and therapy monitoring in glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency)]. Hanefeld, F; Herberg, KP; Hoffmann, GF; Hunneman, DH; Lawrenz-Wolf, B; Lehnert, W, )	0.47
"Treatment with valproic acid and clonazepam completely controlled the seizures in all three patients."	( [Reading-induced epilepsy: three new cases]. Abad, F; Iñiguez, C; Jericó, I; Mauri, JA; Morales, F; Mostacero, E, 1997)	0.64
"Treatment with valproic acid greatly diminished the frequency of myoclonic jerks with minimal side effects."	( Spinal myoclonus complicating spasticity in spinal cord injury: a case study. Andary, MT; Green, DF; Hulce, VD; Pysh, JJ, 1997)	0.64
"The treatment with valproic acid (VPA) and clonazepam (CZP), has been very effective."	( [Atypical benign partial epilepsy of childhood. Clinical follow-up EEG study of 3 patients]. Bauzano-Poley, E; Delgado-Marqués, MP; Mora-Ramírez, MD; Rodríguez-Barrionuevo, AC; Tosina-García, E, 1998)	0.62

Toxicity

Valproic acid and its derivatives are effective in the treatment of some epileptic seizures. Polytherapy is commonly reported and seems to be a risk factor for hepatotoxicity, pancreatitis and other serious adverse drug reactions.

Excerpt	Reference	Relevance
" This side effect should be considered in the management of dental patients taking the drug for whom treatment involves surgery of the soft tissues."	( Valproic acid: a new antiepileptic drug with potential side effects of dental concern. Hassell, TM; Jewson, LG; Peele, LC; White, GC, 1979)	1.7
" These deal mainly with biochemical systems that are known to be affected by VPA, or with the possible idiosyncratic production of toxic VPA metabolites, especially delta 4-VPA."	( Valproate hepatotoxicity syndrome: hypotheses of pathogenesis. Levy, RH; Stephens, JR, 1992)	0.28
" It is concluded that 2-EH is not developmentally toxic by the dermal route in the Fischer 344 rat at and below treatment levels which produce maternal toxicity."	( The developmental toxicity of 2-ethylhexanol applied dermally to pregnant Fischer 344 rats. Astill, BD; Fisher, LC; Gingell, R; Guest, D; Hodgson, JR; Kubena, MF; Murphy, SR; Tyl, RW; Tyler, TR; Vrbanic, MA, 1992)	0.28
" Our results indicate that all three risk factors clearly increase the metabolic conversion of VPA to 4-en, the most toxic VPA metabolite, and that polytherapy and high VPA serum level result in the inhibited beta-oxidative metabolism of VPA to 2-en."	( Associations between risk factors for valproate hepatotoxicity and altered valproate metabolism. Fukushima, Y; Hirano, T; Ishida, M; Kaneko, S; Koide, N; Kondo, T; Muranaka, H; Otani, K; Yokoyama, M, )	0.13
"Rare, serious adverse effects of antiepileptic drugs (AEDs) include hepatotoxicity and bone marrow suppression."	( Routine laboratory monitoring for serious adverse effects of antiepileptic medications: the controversy. Wyllie, E; Wyllie, R, 1991)	0.28
" With respect to pathogenesis attention has focused on depletion of beta-oxidation and change of biotransformation to other pathways with increased synthesis of toxic unsaturated VPA derivates."	( [Valproate-associated hepatotoxicity--pathogenesis, clinical aspects, therapy and prevention]. Nau, H; Siemes, H, )	0.13
"Although valproic acid as well as its derivatives are effective in the treatment of some epileptic seizures, they are not free of adverse side effects."	( [Adverse effects of valproic acid in epileptic infants and adolescents]. Blumel, JE; Devilat, M, )	0.87
"The joint toxic action of three binary mixtures was determined for the embryo malformation endpoint of the aquatic FETAX (frog embryo teratogenesis assay: Xenopus) test system."	( Initial evaluation of developmental malformation as an end point in mixture toxicity hazard assessment for aquatic vertebrates. Dawson, DA; Wilke, TS, 1991)	0.28
" The pathogenesis of VPA hepatotoxicity is unclear but may relate to the accumulation of a toxic metabolite of VPA which impairs fatty-acid oxidation."	( The high incidence of valproate hepatotoxicity in infants may relate to familial metabolic defects. Applegarth, DA; Appleton, RE; Davidson, AG; Dimmick, JE; Farrell, K; Wong, LT, 1990)	0.28
" By analogy with certain spontaneous and acquired human disorders of branched chain amino acid metabolism, it is suggested that valproate-associated hepatotoxicity may represent the consequences of a valproate overload on a limited mitochondrial beta-oxidation capacity, causing accumulation of a toxic product of endogenous branched chain amino acid metabolism."	( Valproate metabolism during hepatotoxicity associated with the drug. Dickinson, RG; Dunstan, PR; Eadie, MJ; MacLaughlin, D; McKinnon, GE, 1990)	0.28
" On the other hand, sodium valproate and isoniazid was, respectively, seven and 100 times more toxic for embryos than adults, thus indicating that these pharmaceuticals might pose developmental hazards to mammalian development."	( In vitro testing for developmental toxicity using the Hydra attenuata assay. Støttum, A; Wiger, R, 1985)	0.27
" for 6 weeks, and anticonvulsant and adverse effects during this period were studied."	( Valproic acid in amygdala-kindled rats: alterations in anticonvulsant efficacy, adverse effects and drug and metabolite levels in various brain regions during chronic treatment. Fisher, JE; Hönack, D; Löscher, W; Nau, H, 1989)	1.72
" A review of biochemical pathways lends support to the argument that toxicity is due to certain toxic metabolites."	( [Clinical and physiopathologic study of the hepatotoxicity of psychotropic drugs including the antiepileptics]. Ferrey, G; Sicot, C, )	0.13
" Twenty-three patients complained of various long-term adverse effects, while the other 17 remained symptom-free."	( Long-term treatment with sodium valproate: monitoring of venous ammonia concentrations and adverse effects. Arnetoli, G; Campostrini, R; Messori, A; Paganini, M; Valenza, T; Zaccara, G; Zappoli, R, 1987)	0.27
" Four of the patients, all on polytherapy, had had short-term adverse effects during chronic VPA treatment, and in them there has been abnormal NH3-values after a test doese of VPA."	( Lack of relationship between sodium valproate-induced adverse effects and the plasma concentration of its metabolite 2-propylpenten-4-oic acid. Arnetoli, G; Bendoni, L; Campostrini, R; Moroni, F; Paganini, M; Zaccara, G; Zappoli, R, 1987)	0.27
" These results show that barbiturates should not be first-choice drugs in patients who have a chronic disease such as epilepsy, and indicate a schedule for barbiturate withdrawal which is safe and independent of hospitalization or monitoring of antiepileptic drug serum concentrations."	( Barbiturate-refractory epilepsy: safe schedule for therapeutic substitution. Bittencourt, PR; Gorz, AM; Silvado, CE, 1986)	0.27
" The VPA-400 dose was maternally toxic in as much as maternal weight gain was reduced, but no deaths occurred."	( Teratogenicity and developmental toxicity of valproic acid in rats. Vorhees, CV, 1987)	0.53
" Our study shows that VPA is a safe treatment in epileptic patients with PCT."	( Safety of valproate in porphyria cutanea tarda. Baldrati, A; Baruzzi, A; Benassi, G; Cassanelli, M; Cristina, E; D'Alessandro, R; Pizzino, D; Rocchi, E, )	0.13
" This defect may divert valproate metabolism towards omega-oxidation, with increased formation of the toxin 4-en-valproate, but may also allow increased formation of a toxic metabolite derived from isoleucine, since beta-oxidation of isoleucine derivatives will also be impaired."	( Valproate-associated hepatotoxicity and its biochemical mechanisms. Dickinson, RG; Eadie, MJ; Hooper, WD, )	0.13
" Indeed, although some form of side effect occurred in 50% of patients, treatment had to be changed in only 18% and the drug had to be stopped in only 7%."	( Clinical side effects of phenobarbital, primidone, phenytoin, carbamazepine, and valproate during monotherapy in children. Armijo, JA; Arteaga, R; Herranz, JL, )	0.13
" Accordingly, camptocormia is a dose-dependent side effect of valproate."	( Camptocormia, a new side effect of sodium valproate. Iivanainen, M; Kiuru, S, 1987)	0.27
" In many situations, the final choice of an antiepileptic drug is based upon an agent's side-effect profile."	( Side effects of valproate. Dreifuss, FE; Langer, DH, 1988)	0.27
" It is postulated that the idiosyncratic response in OTC-deficient mice may be caused by an interaction between a metabolic aberration of mitochondria and toxic metabolites of valproate."	( Hepatotoxicity of sodium valproate in ornithine transcarbamylase-deficient mice. Letarte, J; Qureshi, IA; Qureshi, SR; Tuchweber, B; Yousef, I, 1985)	0.27
" Toxic effects were generally mild."	( Valproic acid therapy for complex partial seizures. Its efficacy and toxic effects. Albright, P; Bruni, J, 1983)	1.71
" The sodium salts of three metabolites, 2-propylpent-4-enoate, 4-hydroxyvalproate, and perhaps 5-hydroxyvalproate, were toxic in this system."	( The toxicity of metabolites of sodium valproate in cultured hepatocytes. Gray, P; Kingsley, E; Tolman, KG; Tweedale, R, 1983)	0.27
" However, whereas toxic reactions following phenytoin and carbamazepine are characterised by a rather short duration of exposure before symptoms occur with accompanying clinical features of hypersensitivity, valproate-induced hepatic toxicity exhibits no signs of hypersensitivity and often occurs following prolonged exposure, speaking in favor of a metabolic aberration as the underlying cause."	( Hepatic toxicity of antiepileptic drugs: a review. Bentsen, KD; Gram, L, 1983)	0.27
" Adverse events, laboratory studies performed, and seizure activity were documented on case report forms."	( Safety of intravenous valproate. Dean, C; Devinsky, O; Gates, J; Leppik, I; Pellock, JM; Ramsay, RE; Willmore, LJ, 1995)	0.29
"Development of novel antiepileptic drugs (AEDs) requires determining the margin between the desired anticonvulsant effect and undesired adverse effects (AE) (therapeutic index)."	( Kindling increases the sensitivity of rats to adverse effects of certain antiepileptic drugs. Hönack, D; Löscher, W, 1995)	0.29
" Valproate caused a dose-dependent increase in leakage of lactic acid dehydrogenase (LDH), and glycine prevented this toxic response."	( Effect of glycine on valproate toxicity in rat hepatocytes. Gray, PD; Tolman, KG; Vance, MA, )	0.13
" A review of the literature associated with our personal experience since 1976 has shown VPA to be a remarkably safe and effective antiepileptic drug in a wide range of epileptic conditions in children and adults."	( [Tolerance to and unwanted effects of valproate sodium]. Despland, PA, 1994)	0.29
" Hepatotoxicity is the most serious adverse reaction and, although rare, it can be fatal."	( [Hepatotoxicity induced by valproic acid in adults. Report of 3 cases]. Aguilera, L; Chesta, J; Galdames, D; Silva, C, 1993)	0.58
"5-5 mg/kg, CGP 37849 potentiated the adverse effects but not the anticonvulsant activity of 50 mg/kg valproate."	( Effects of the competitive NMDA receptor antagonist, CGP 37849, on anticonvulsant activity and adverse effects of valproate in amygdala-kindled rats. Hönack, D; Löscher, W, 1993)	0.29
" In 11 patients with early symptoms and signs of possible fatal VPA-associated hepatotoxicity, the following spectrum of benign clinical conditions was observed: unusually severe side effect during initiation of VPA therapy (1 patient), high VPA dosage (2 patients), reversible impairment of coagulation with bleeding manifestations in association with a slight increase in transaminase levels (1 child), and reversible liver dysfunction associated with febrile illness (7 patients)."	( Valproate (VPA) metabolites in various clinical conditions of probable VPA-associated hepatotoxicity. Drews, E; Nau, H; Penzien, J; Schultze, K; Seidel, U; Siemes, H; Wittfoht, W, )	0.13
" Adverse events did not change significantly."	( Pharmacokinetic interactions and side effects resulting from concomitant administration of lithium and divalproex sodium. Cavanaugh, JH; Granneman, GR; Schneck, DW; Witt, GF, 1996)	0.29
"Concomitant administration of lithium and valproate appears to be safe in patients with bipolar disorder."	( Pharmacokinetic interactions and side effects resulting from concomitant administration of lithium and divalproex sodium. Cavanaugh, JH; Granneman, GR; Schneck, DW; Witt, GF, 1996)	0.29
" Adverse events that occurred significantly more frequently in the high group included tremors, thrombocytopenia, alopecia, asthenia, diarrhea, vomiting, and anorexia."	( Safety and efficacy of divalproex sodium monotherapy in partial epilepsy: a double-blind, concentration-response design clinical trial. Depakote Monotherapy for Partial Seizures Study Group. Beydoun, A; Sackellares, JC; Shu, V, 1997)	0.3
"In this preliminary report from a placebo-controlled, double-blind, dose-response study on the use of pergolide mesylate for cocaine dependence in outpatients 8 out of 235 subjects noted adverse events requiring breaking of the blind."	( Pergolide mesylate. Adverse events occurring in the treatment of cocaine dependence. Cochrane, CE; Kajdasz, DK; Malcolm, R; Moore, JW, 1997)	0.3
"Attention for adverse effects (AEs) is important for optimizing epilepsy treatment."	( Adverse effects in epilepsy therapy. Wait and see or go for it? Deckers, CL; Hekster, YA; Keyser, A; Lammers, MW; Meinardi, H; Renier, WO, 1997)	0.3
" AWD 140-190 thus presents an orally active and safe anticonvulsant agent, which is structurally unrelated to anticonvulsants currently used."	( AWD 140-190: a new anticonvulsant with a very good margin of safety. Bartsch, R; Engel, J; Rostock, A; Rundfeldt, C; Tober, C; Unverferth, K; White, HS; Wolf, HH, 1997)	0.3
" One general rule that may reduce the risks of toxic drug interactions is to add medication to the patient's current regimen in modest doses and increase the dose slowly."	( Mood stabilizer combinations: a review of safety and efficacy. Freeman, MP; Stoll, AL, 1998)	0.3
" Toxic damage of CNS was the most significant."	( [Side effects of anticonvulsants in the treatment of idiopathic generalized epilepsy]. Mukhin, KIu; Petrukhin, AS; Rykova, EA, 1997)	0.3
" In the present work the effects of developmentally toxic doses of 2-ethylhexanoic acid (EHXA), 2-ethylhexanol (EHXO), and valproic acid (VPA) on Zn metabolism were investigated in the pregnant rat."	( Altered zinc metabolism contributes to the developmental toxicity of 2-ethylhexanoic acid, 2-ethylhexanol and valproic acid. Bui, LM; Commisso, JF; Faber, WD; Keen, CL; Taubeneck, MW; Uriu-Hare, JY, 1998)	0.72
" This review summarizes efficacy results of key studies in manic-depressive illness, the increasingly practical findings regarding predictors of response, and the implications of the increasingly better understood adverse effect profile of lithium."	( Key treatment studies of lithium in manic-depressive illness: efficacy and side effects. Bowden, CL, 1998)	0.3
"Pancreatitis is a serious adverse effect of valproic acid (VPA)."	( On the toxicity of valproic-acid. Alonso, R; Cuiña, L; Moreiras Plaza, M; Rodríguez Goyanes, G, 1999)	0.56
" Patients treated with divalproex sodium compared with patients treated with valproic acid were less likely to experience gastrointestinal side effects and to have discontinued their medication because of an adverse event."	( The adverse effect profile and efficacy of divalproex sodium compared with valproic acid: a pharmacoepidemiology study. Madrid, AR; McDonald, J; Narendran, R; Sederer, M; Tohen, M; Tomassini, EC; Zarate, CA, 1999)	0.76
"This study compares the incidence, severity and onset of treatment-emergent adverse effects between slow titration and loading of divalproex sodium in psychiatric inpatients."	( A naturalistic comparison of adverse effects between slow titration and loading of divalproex sodium in psychiatric inpatients. Dopheide, JA; Earhart, CA; Kramer, BA; Lima, WJ; Wincor, MZ, )	0.13
" Under single-blind conditions, adverse effects were assessed using a valproate adverse effects rating scale."	( A naturalistic comparison of adverse effects between slow titration and loading of divalproex sodium in psychiatric inpatients. Dopheide, JA; Earhart, CA; Kramer, BA; Lima, WJ; Wincor, MZ, )	0.13
"Overall, adverse effects were well tolerated by both groups."	( A naturalistic comparison of adverse effects between slow titration and loading of divalproex sodium in psychiatric inpatients. Dopheide, JA; Earhart, CA; Kramer, BA; Lima, WJ; Wincor, MZ, )	0.13
" About 1% to 2% of exposed fetuses suffer adverse effects."	( Safe use of valproic acid during pregnancy. Kennedy, D; Koren, G, 1999)	0.68
" Two analyses of adverse events are presented: tolerability and safety."	( Safety and tolerability of gabapentin as adjunctive therapy in a large, multicenter study. Bernstein, P; Faught, RE; Holmes, GL; Magnus-Miller, L; McLean, MJ; Morrell, MJ; Privitera, MD; Rose-Legatt, A; Willmore, LJ, 1999)	0.3
" Within these 281 patients, two mutually exclusive groups were compared (a) those reporting adverse events at only < or =1,800 mg/day (low dose); and (b) those reporting adverse events at only >1,800 mg/day (high dose)."	( Safety and tolerability of gabapentin as adjunctive therapy in a large, multicenter study. Bernstein, P; Faught, RE; Holmes, GL; Magnus-Miller, L; McLean, MJ; Morrell, MJ; Privitera, MD; Rose-Legatt, A; Willmore, LJ, 1999)	0.3
"Gabapentin doses >1,800 mg/day were as well tolerated as doses < or =1,800 mg/day and were not associated with more adverse events."	( Safety and tolerability of gabapentin as adjunctive therapy in a large, multicenter study. Bernstein, P; Faught, RE; Holmes, GL; Magnus-Miller, L; McLean, MJ; Morrell, MJ; Privitera, MD; Rose-Legatt, A; Willmore, LJ, 1999)	0.3
" The adverse effect (AE) profile of this combination needs clarification."	( Adding lamotrigine to valproate: incidence of rash and other adverse effects. Postmarketing Antiepileptic Drug Survey (PADS) Group. Faught, E; French, J; Harden, C; Jacobson, M; Montouris, G; Morris, G; Rosenfeld, W, 1999)	0.3
" It has a relatively benign side effect profile, but little data exists on massive overdoses with this agent."	( A case of sustained massive gabapentin overdose without serious side effects. Radtke, RA; St Clair, EW; Verma, A, 1999)	0.3
" No patient was removed from the study because of an adverse event."	( Safety and tolerability of oral loading divalproex sodium in acutely manic bipolar patients. Allen, MH; Hirschfeld, RM; Keck, PE; McEvoy, JP; Russell, JM, 1999)	0.3
"Accelerated oral loading with divalproex sodium is a feasible and safe method to bring serum valproate concentrations to effective levels rapidly."	( Safety and tolerability of oral loading divalproex sodium in acutely manic bipolar patients. Allen, MH; Hirschfeld, RM; Keck, PE; McEvoy, JP; Russell, JM, 1999)	0.3
" Potential adverse effects such as thrombocytopenia and leukopenia are easily detected by laboratory monitoring, which should be continued indefinitely at least on a quarterly basis."	( Hematologic toxicity of sodium valproate. Acharya, S; Bussel, JB, )	0.13
" In this study, we examined the anticonvulsant and adverse effects of the three clinically established AEDs carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) once per month in the same two groups of amygdala-kindled rats over a period of 9 (group 1) or 6 (group 2) consecutive months."	( Repeated acute testing of anticonvulsant drugs in amygdala kindled rats: increase in anticonvulsant but decrease in adverse effect potential. Fiedler, M; Löscher, W, 2000)	0.31
"These data demonstrate that repeated use of the same kindled rats for acute drug testing significantly alters the sensitivity of the animals to the anticonvulsant and adverse effects of drugs."	( Repeated acute testing of anticonvulsant drugs in amygdala kindled rats: increase in anticonvulsant but decrease in adverse effect potential. Fiedler, M; Löscher, W, 2000)	0.31
" Further increment in dose was carried out at weekly intervals, guided by clinical improvement, serum levels and treatment emergent adverse events."	( Carbamazepine and valproate monotherapy: feasibility, relative safety and efficacy, and therapeutic drug monitoring in manic disorder. Goswami, U; Kohli, K; Vasudev, K, 2000)	0.31
" Significantly more patients in the CBZ group reported adverse events, including nausea, vomiting and dizziness, than VPA."	( Carbamazepine and valproate monotherapy: feasibility, relative safety and efficacy, and therapeutic drug monitoring in manic disorder. Goswami, U; Kohli, K; Vasudev, K, 2000)	0.31
" Valproic acid alone was not toxic to hepatocytes even at ten times higher concentrations (10 mmol/l), suggesting that cell damage was not a mere additive effect."	( Evidence for a trigger function of valproic acid in xenobiotic-induced hepatotoxicity. Johanssen, S; Klee, S; Ungemach, FR, 2000)	1.49
" Treatment was discontinued in 7% because of adverse events."	( Open study evaluating lamotrigine efficacy and safety in add-on treatment and consecutive monotherapy in patients with carbamazepine- or valproate-resistant epilepsy. Jozwiak, S; Terczynski, A, 2000)	0.31
" No serious adverse effects attributable to the rapid infusion of valproic acid were encountered, although valproic acid, along with other factors, may have contributed to the hypotension in two patients."	( The safety of rapid valproic acid infusion. Faught, E; Limdi, NA, 2000)	0.87
" However, on rare occasions, they can progress to more severe cutaneous disorders, including Stevens-Johnson syndrome and toxic epidermal necrolysis."	( Therapeutic safety monitoring: what to look for and when to look for it. Harden, CL, 2000)	0.31
" 23 patients (30%) had at least one adverse event (AE), but only 1/4 of all AEs might be reasonably regarded as an effect of the medication."	( [Open study evaluating lamotrigine efficacy and safety in add-on treatment and consecutive monotherapy in adult patients with epilepsy resistant carbamazepine and valproate]. Jóźwiak, S; Mańko, E; Niedzielska, K; Terczyński, A, )	0.13
" Lamotrigine is a safe and well-tolerated drug."	( [Open study evaluating lamotrigine efficacy and safety in add-on treatment and consecutive monotherapy in adult patients with epilepsy resistant carbamazepine and valproate]. Jóźwiak, S; Mańko, E; Niedzielska, K; Terczyński, A, )	0.13
"The adverse event profile of long-term divalproex therapy for epilepsy is well established, but little is known about the tolerability or safety of divalproex in long-term migraine prophylaxis."	( Safety of divalproex sodium in migraine prophylaxis: an open-label, long-term study. Long-term Safety of Depakote in Headache Prophylaxis Study Group. Collins, SD; Silberstein, SD, 1999)	0.3
"Number and proportion of patients reporting treatment-emergent adverse events, prevalence and incidence for each treatment-emergent adverse event, vital signs, body weight, 4-week migraine rates and proportion of patients with 50% or greater reduction in rate over time."	( Safety of divalproex sodium in migraine prophylaxis: an open-label, long-term study. Long-term Safety of Depakote in Headache Prophylaxis Study Group. Collins, SD; Silberstein, SD, 1999)	0.3
" This adverse event should be managed with caution."	( Nitroso-urea-cisplatin-based chemotherapy associated with valproate: increase of haematologic toxicity. Bourg, V; Chichmanian, RM; Frenay, M; Lebrun, C; Thomas, P, 2001)	0.31
" The most common adverse effect was paresthesia (n= 2)."	( [Effectiveness and safety of topiramate in treatment-resistant bipolar disorder]. Arrufat, E; García-Castrillón, A; García-Parés, G; Gilabert, A; Luna, MJ; Rodríguez, A; Vieta, E, )	0.13
" Our case reports suggest that possible adverse effects of VPA should be given particular attention when VPA is combined with TPM."	( Topiramate enhances the risk of valproate-associated side effects in three children. Koelfen, W; König, S; Longin, E; Teich, M, 2002)	0.31
"1%) had a detectable initial concentration not in the toxic range, and 5 (2."	( Delayed valproic acid toxicity: a retrospective case series. Beauchamp, J; Clark, RF; Ingels, M; Williams, SR, 2002)	0.75
" Serial measurements documenting declining VPA concentrations or prolonged observation are recommended to determine whether a patient is medically safe for discharge or psychiatric placement."	( Delayed valproic acid toxicity: a retrospective case series. Beauchamp, J; Clark, RF; Ingels, M; Williams, SR, 2002)	0.75
" Other safety and tolerability endpoints included spontaneous adverse event reporting and changes from baseline in laboratory measures and vital signs."	( A comparison of the efficacy, safety, and tolerability of divalproex sodium and olanzapine in the treatment of bipolar disorder. Sachs, G; Sommerville, KW; Swann, AC; Weisler, R; Wozniak, P; Zajecka, JM, 2002)	0.31
"05) greater proportion of olanzapine-treated subjects experienced somnolence, weight gain, edema, rhinitis, and speech disorder (slurred speech); no adverse events were significantly greater in the divalproex group."	( A comparison of the efficacy, safety, and tolerability of divalproex sodium and olanzapine in the treatment of bipolar disorder. Sachs, G; Sommerville, KW; Swann, AC; Weisler, R; Wozniak, P; Zajecka, JM, 2002)	0.31
" Divalproex was associated with a more favorable adverse event profile and significantly less weight gain than olanzapine."	( A comparison of the efficacy, safety, and tolerability of divalproex sodium and olanzapine in the treatment of bipolar disorder. Sachs, G; Sommerville, KW; Swann, AC; Weisler, R; Wozniak, P; Zajecka, JM, 2002)	0.31
" Similar proportions of subjects in the two groups reported adverse events during or within 6 h following the first infusion."	( Safety and tolerance of rapidly infused Depacon. A randomized trial in subjects with epilepsy. Cantrell, D; Cloyd, JC; Collins, SD; Naritoku, DK; Ramsay, RE; Sommerville, K; Walch, JK, 2003)	0.32
" Side effects were assessed using the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale."	( Safety and efficacy of switching psychiatric patients from a delayed-release to an extended-release formulation of divalproex sodium. Cunanan, C; Horne, RL, 2003)	0.32
" A nonsignificant increase in the rate of adverse events was noted in the intravenous group."	( Acute antimanic efficacy and safety of intravenous valproate loading therapy: an open-label study. Akhtar, S; Basu, S; Duggal, H; Gupta, S; Jagadheesan, K; Nizamie, SH; Ranjan, S; Sandil, R, 2003)	0.32
"Intravenous VPA loading is safe and effective for treating acute seizure emergencies in children."	( Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures. Cunanan, C; Mills, S; Thompson, N; Yu, KT, 2003)	0.32
" Divalproex loading was as well tolerated or better tolerated than the other active treatments as measured by adverse events and changes in laboratory parameters."	( The safety and early efficacy of oral-loaded divalproex versus standard-titration divalproex, lithium, olanzapine, and placebo in the treatment of acute mania associated with bipolar disorder. Baker, JD; Hirschfeld, RM; Sommerville, KW; Tracy, K; Wozniak, P, 2003)	0.32
"Morphea, a specific type of cutaneous sclerosis, is known in the pediatric age group, but not as an adverse effect to the antiepileptic valproic acid."	( Localized morphea: a rare adverse effect of valproic acid. El-Tal, Ael-K; Ferzli, GT; Kibbi, AG; Mikati, MA, 2003)	0.78
" The toxic potential resulting from our data would be valproic acid < cyclosporine A < amiodarone."	( Cytotoxicity evaluation after coexposure to perchloroethylene and selected peroxidant drugs in rat hepatocytes. Barbaro, M; Catania, S; Costa, C; Germanò, MP; Silvari, V, 2004)	0.57
" Measured at baseline and end point were the Brief Psychiatric Rating Scale and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale."	( A study of the safety, efficacy, and tolerability of switching from the standard delayed release preparation of divalproex sodium to the extended release formulation in patients with schizophrenia. Citrome, L; Dinakar, H; Roy, B; Tremeau, F; Wynn, PS, 2004)	0.32
" Seven patients experienced spontaneously reported adverse events, but none required early termination from the protocol."	( A study of the safety, efficacy, and tolerability of switching from the standard delayed release preparation of divalproex sodium to the extended release formulation in patients with schizophrenia. Citrome, L; Dinakar, H; Roy, B; Tremeau, F; Wynn, PS, 2004)	0.32
" At the time of deterioration, serum valproate was at toxic level in the three reported cases."	( Delayed toxicity following acute ingestion of valpromide. Descotes, J; Frantz, P; Martin, O; Moulsma, M; Parant, F; Payen, C; Pulce, C, 2004)	0.32
" Adverse events reported by two or more subjects were abdominal pain and somnolence for the morning dosing regimen and asthenia, headache, and pain for the evening dosing regimen."	( Pharmacokinetics and safety of extended-release divalproex sodium tablets: morning versus evening administration. Cavanaugh, JH; Dutta, S; Reed, RC, 2004)	0.32
" Therefore, adverse effects occurred more often in barbiturates than in valproate treatment both for mono- and polytherapy (p<0."	( [Efficacy and safety of antiepileptic therapy in children (a comparative analysis of valproates and barbiturates)]. Petrukhin, AS; Pylaeva, OA; Voronkova, KV, 2004)	0.32
"Two hundred fifty-one L-carnitine doses were not associated with adverse or toxic effects in our VPA toxic patients."	( L-carnitine was safely administered in the setting of valproate toxicity. LoVecchio, F; Samaddar, R; Shriki, J, 2005)	0.33
" Adverse events and reasons for terminating the diet were tabulated."	( Safety and tolerability of the ketogenic diet in pediatric epilepsy: effects of valproate combination therapy. Ghosh, S; Lyczkowski, DA; Pfeifer, HH; Thiele, EA, 2005)	0.33
" The most serious adverse events were two cases of acute pancreatitis (2."	( Safety and tolerability of the ketogenic diet in pediatric epilepsy: effects of valproate combination therapy. Ghosh, S; Lyczkowski, DA; Pfeifer, HH; Thiele, EA, 2005)	0.33
"KGD and VPA combination therapy is relatively safe and effective in refractory pediatric epilepsy."	( Safety and tolerability of the ketogenic diet in pediatric epilepsy: effects of valproate combination therapy. Ghosh, S; Lyczkowski, DA; Pfeifer, HH; Thiele, EA, 2005)	0.33
" Several studies or isolated clinical observations have suggested the potential value of oral L-carnitine in reversing carnitine deficiency or preventing its development as well as some adverse effects due to VPA."	( Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence? Gris, M; Lheureux, PE; Penaloza, A; Zahir, S, 2005)	0.59
" The rate of patients discontinuing treatment due to adverse events or a lack of efficacy was 19% with CBZ compared to 9% with LTG (not statistically different)."	( The LAM-SAFE Study: lamotrigine versus carbamazepine or valproic acid in newly diagnosed focal and generalised epilepsies in adolescents and adults. Bergmann, L; Kurlemann, G; Schmitz, B; Siemes, H; Steinhoff, BJ; Ueberall, MA, 2005)	0.57
"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
" Therefore, the authors summarise adverse events of greatest prevalence and/or greatest severity based on data derived predominately from studies of geriatric patients with epilepsy and/or other non-psychiatric indications."	( Safety and tolerability of mood-stabilising anticonvulsants in the elderly. Alldredge, B; Fenn, HH; Ketter, TA; Sommer, BR, 2006)	0.33
" Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications."	( Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. Carlson, HE; Correll, CU, 2006)	0.33
"Clinicians and caregivers need to be aware of potential endocrine and metabolic adverse effects of psychiatric medications."	( Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. Carlson, HE; Correll, CU, 2006)	0.33
" VPA is a relatively safe drug, but its use is associated with idiosyncratic hepatotoxicity, which in some cases may lead to fatality."	( Oxidative stress as a mechanism of valproic acid-associated hepatotoxicity. Abbott, FS; Chang, TK, 2006)	0.61
" Only one adverse event was reported; a 9-year-old male experienced burning at the infusion site while receiving 660 mg intravenous valproate at 6 mg/kg per minute."	( Safety of rapid intravenous valproate infusion in pediatric patients. Coots, BP; Morton, LD; O'Hara, KA; Pellock, JM, 2007)	0.34
" However it was reported that it may cause adverse effects such as liver failure and hepatitis, which arouses the attention of the medical field."	( [An experimental study on hepatotoxicity of topiramate in young rats]. Chen, XM; Huang, J; Ren, RN; Ye, LY, 2007)	0.34
"Rapid administration of undiluted valproate is safe and well tolerated at infusion rate up to 10 mg/kg/min and doses of up to 30 mg/kg."	( Safety of rapid intravenous loading of valproate. Cofield, SS; Dutta, S; Faught, E; Knowlton, RK; Limdi, NA; Paige, AL; Ver Hoef, LW, 2007)	0.34
"Sodium valproate (VPA), a common treatment of epilepsy and other diseases, is known to have severe toxic effects on testis both in experimental animals and in humans."	( Apium graveolens modulates sodium valproate-induced reproductive toxicity in rats. Amin, A; Hamza, AA, 2007)	0.34
"As pharmacokinetic drug interactions frequently cause adverse events, it is important that the relevant information is given in package inserts (PIs)."	( Adverse events caused by drug interactions involving glucuronoconjugates of zidovudine, valproic acid and lamotrigine, and analysis of how such potential events are discussed in package inserts of Japan, UK and USA. Hasegawa, R; Hirata-Koizumi, M; Miyake, S; Saito, M, 2007)	0.56
"We reviewed clinical drug interactions related to glucuronoconjugates, focusing on reports of adverse events."	( Adverse events caused by drug interactions involving glucuronoconjugates of zidovudine, valproic acid and lamotrigine, and analysis of how such potential events are discussed in package inserts of Japan, UK and USA. Hasegawa, R; Hirata-Koizumi, M; Miyake, S; Saito, M, 2007)	0.56
" Of these, five combinations induced clear adverse events: (i) severe anaemia due to zidovudine and caused by interaction with valproic acid, (ii) recurrence/increased frequency of seizure or increased manic states from a reduction in therapeutic effects of valproic acid caused by panipenem, (iii) meropenem or (iv) ritonavir and (v) of lamotrigine caused by oral contraceptives."	( Adverse events caused by drug interactions involving glucuronoconjugates of zidovudine, valproic acid and lamotrigine, and analysis of how such potential events are discussed in package inserts of Japan, UK and USA. Hasegawa, R; Hirata-Koizumi, M; Miyake, S; Saito, M, 2007)	0.77
"Five combinations were identified to cause severe adverse events because of interactions related to glucuronoconjugates."	( Adverse events caused by drug interactions involving glucuronoconjugates of zidovudine, valproic acid and lamotrigine, and analysis of how such potential events are discussed in package inserts of Japan, UK and USA. Hasegawa, R; Hirata-Koizumi, M; Miyake, S; Saito, M, 2007)	0.56
" Adverse event reporting, Simpson Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) scores were recorded."	( Safety and tolerability of quetiapine in the treatment of acute mania in bipolar disorder. Adler, CM; Brecher, M; Fleck, DE; Strakowski, SM, 2007)	0.34
"Most adverse events were mild to moderate."	( Safety and tolerability of quetiapine in the treatment of acute mania in bipolar disorder. Adler, CM; Brecher, M; Fleck, DE; Strakowski, SM, 2007)	0.34
" Isolated pediatric case reports show that carnitine administration may reverse toxic metabolic pathways but may not hasten clinical improvement."	( Carnitine as an antidote for acute valproate toxicity in children. Russell, S, 2007)	0.34
" In conclusion, the combination studied is safe and has significant clinical activity."	( Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Cortes, J; Estey, EH; Estrov, Z; Faderl, S; Garcia-Manero, G; Giles, F; Issa, JP; Kantarjian, HM; Ouzounian, S; Pierce, S; Quezada, A; Ravandi, F; Soriano, AO; Wierda, WG; Yang, H, 2007)	0.58
" Adverse drug reactions (hair loss and tremor) were recorded in <20% of patients, mostly affecting adults."	( Short-term efficacy and safety of valproate sustained-release formulation in newly diagnosed partial epilepsy VIPe-study. A multicenter observational open-label study. Al-Hail, H; Deleu, D; Mahmoud, HA; Mesraoua, B, 2007)	0.34
" The supplier group was much more sensitive to these toxic effects."	( Valproate-induced developmental neurotoxicity is affected by maternal conditions including shipping stress and environmental change during early pregnancy. Hori, Y; Kuwagata, M; Ogawa, T; Shioda, S, 2007)	0.34
" Administration of 300 mg/day of DPH in this patient resulted in toxic symptoms associated with an excessive serum DPH concentration of 33 microg/ml."	( Severe phenytoin toxicity in a CYP2C9*3*3 homozygous mutant from India. Chandrasekaran, A; Chanolean, S; Narayan, SK; Ramasamy, K, )	0.13
" During the randomization phase, the most common adverse events occurring in > or =5% in the quetiapine group were somnolence, nasopharyngitis, and headache."	( Efficacy and safety of quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar I disorder (international trial 126). Brecher, M; Eggens, I; Paulsson, B; Persson, I; Suppes, T; Vieta, E, 2008)	0.35
" This case report indicates that even non-chronic MDMA use may cause subacute toxic encephalopathy in which the clinical evolution is paralleled by neuroimaging changes in specific cerebral areas."	( Hippocampal remodelling after MDMA neurotoxicity: a single case study. Amistà, P; Battaglia, M; Bertagnoni, GE; Carollo, C; Costanzo, R; Lupi, A; Martinuzzi, A; Nifosì, F; Perini, G; Toffanin, T; Vestri, A, 2009)	0.35
" Subjects from the previous trial who had experienced serious adverse events possibly or probably related to study drug were excluded."	( Safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches: results of an open-label extension trial in adolescents. Abi-Saab, WM; Apostol, G; Laforet, GA; Olson, E; Pakalnis, A; Robieson, WZ; Saltarelli, M, 2009)	0.35
" The most common adverse events were weight gain (15%), nausea (14%), somnolence (12%), upper respiratory tract infection (11%), increased ammonia (8%), and sinusitis (8%)."	( Safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches: results of an open-label extension trial in adolescents. Abi-Saab, WM; Apostol, G; Laforet, GA; Olson, E; Pakalnis, A; Robieson, WZ; Saltarelli, M, 2009)	0.35
" Safety was evaluated by adverse event collection, laboratory assessments, physical and neurological examinations, vital signs, electrocardiograms, the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, the Wechsler Abbreviated Scale of Intelligence, and the Behavioral Assessment Scale for Children."	( Divalproex sodium extended-release for the prophylaxis of migraine headache in adolescents: results of a stand-alone, long-term open-label safety study. Abi-Saab, WM; Apostol, G; Fugate, JM; Laforet, GA; Lewis, DW; Robieson, WZ; Saltarelli, MD, 2009)	0.35
" The most frequently reported adverse events were nausea (19%), vomiting (18%), weight gain (12%), nasopharyngitis (11%), migraine (10%), and upper respiratory tract infection (10%)."	( Divalproex sodium extended-release for the prophylaxis of migraine headache in adolescents: results of a stand-alone, long-term open-label safety study. Abi-Saab, WM; Apostol, G; Fugate, JM; Laforet, GA; Lewis, DW; Robieson, WZ; Saltarelli, MD, 2009)	0.35
" The most common adverse events were weight gain (16%), nausea (9%), and increased appetite (8%)."	( Long-term safety of divalproex sodium extended-release in children and adolescents with bipolar I disorder. Abi-Saab, W; DelBello, M; Greco, N; Kovacs, X; Malhotra, S; Redden, L; Saltarelli, M; Vigna, NV; Wagner, KD; Wilens, TE; Wozniak, P, 2009)	0.35
"DVPX-ER was generally well tolerated in children and adolescents with acute mania, with a side-effect profile similar to that observed in adults."	( Long-term safety of divalproex sodium extended-release in children and adolescents with bipolar I disorder. Abi-Saab, W; DelBello, M; Greco, N; Kovacs, X; Malhotra, S; Redden, L; Saltarelli, M; Vigna, NV; Wagner, KD; Wilens, TE; Wozniak, P, 2009)	0.35
" It is postulated that carnitine supplementation may increase the beta-oxidation of VPA, thereby limiting cytosolic omega-oxidation and the production of toxic metabolites that are involved in liver toxicity and ammonia accumulation."	( Carnitine in the treatment of valproic acid-induced toxicity. Hantson, P; Lheureux, PE, 2009)	0.64
" Adverse events were systematically recorded throughout the study."	( Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study. Chopra, D; Gupta, NK; Kakkar, AK; Kataria, D; Rehan, HS; Unni, KE, 2009)	0.35
" A significantly greater number of patients in divalproex group experienced one or more adverse drug events as compared to patients in the oxcarbazepine group (66."	( Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study. Chopra, D; Gupta, NK; Kakkar, AK; Kataria, D; Rehan, HS; Unni, KE, 2009)	0.35
" Also the overall adverse event profile was found to be superior for oxcarbazepine."	( Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study. Chopra, D; Gupta, NK; Kakkar, AK; Kataria, D; Rehan, HS; Unni, KE, 2009)	0.35
"To evaluate and to compare the possible toxic effects of oxcarbazepine (OXC) and valproic acid (VPA) on retinal ganglion cells (RGCs) in rat."	( Retinal ganglion cell toxicity due to oxcarbazepine and valproic acid treatment in rat. Aktaş, Z; Cansu, A; Erdoğan, D; Goktas, G; Ozdek, S; Serdaroglu, A; Take, G, 2009)	0.83
"OXC seems to be toxic to RGCs at 100mg/kg dose when it is been given as a monotherapy or combined with VPA."	( Retinal ganglion cell toxicity due to oxcarbazepine and valproic acid treatment in rat. Aktaş, Z; Cansu, A; Erdoğan, D; Goktas, G; Ozdek, S; Serdaroglu, A; Take, G, 2009)	0.6
"The aim of this study was to determine and compare the anticonvulsant and acute adverse (neurotoxic) effects of imperatorin and osthole (two natural coumarin derivatives) with valproate (a classical antiepileptic drug) in the maximal electroshock seizure and chimney tests in mice."	( Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate in the maximal electroshock seizure and chimney tests in mice: a comparative study. Andres-Mach, M; Cisowski, W; Czuczwar, SJ; Glensk, M; Glowniak, K; Luszczki, JJ; Wojda, E, 2009)	0.35
" The most common treatment-emergent adverse events in the 169 study patients were typical childhood illnesses: pyrexia (18%), cough (17%), and nasopharyngitis (14%)."	( Divalproex sodium in children with partial seizures: 12-month safety study. Elterman, RD; Lenz, RA; Robieson, WZ; Saltarelli, MD; Vigna, NV, 2009)	0.35
"The aim of this study was to investigate the relationship between hepatotoxicity, levels of glucuronide conjugates of valproic acid (VPA), and the toxic metabolites of VPA (4-ene VPA and 2,4-diene VPA)."	( The relationship between glucuronide conjugate levels and hepatotoxicity after oral administration of valproic acid. Baek, DJ; Chung, BC; Jung, BH; Kim, BJ; Lee, MS; Lee, YJ; Shin, KJ, 2009)	0.78
"Antiepileptic drugs (AEDs) have been widely used in patients with epilepsy but the adverse effects in adult Chinese patients have not been investigated."	( Adverse effects of carbamazepine, phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients. Wang, X; Xi, Z; Yan, Y; Zeng, K, 2010)	0.36
" An adverse effect profile, as well as efficacy of monotherapy, was obtained through a face-to-face interview with the patient at each visit."	( Adverse effects of carbamazepine, phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients. Wang, X; Xi, Z; Yan, Y; Zeng, K, 2010)	0.36
" Overall, 18% of patients experienced adverse effects: for CBZ (25/168; 14."	( Adverse effects of carbamazepine, phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients. Wang, X; Xi, Z; Yan, Y; Zeng, K, 2010)	0.36
" No fatal adverse events occurred."	( Adverse effects of carbamazepine, phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients. Wang, X; Xi, Z; Yan, Y; Zeng, K, 2010)	0.36
" Bipolar disorder treatment was started with carbamazepine, but later it was discontinued due to adverse events and extreme increase of liver transaminases."	( Galactorrhea - side effect of risperidone in combination with depakine chrono in a patient with bipolar disorder. Grahovac, T; Pavlović, E; Peitl, MV; Peitl, V, 2010)	0.36
" Frequently reported adverse events (AEs) that occurred with ARI + LI vs."	( Assessment of safety, tolerability and effectiveness of adjunctive aripiprazole to lithium/valproate in bipolar mania: a 46-week, open-label extension following a 6-week double-blind study. Baudelet, C; Marcus, RN; McQuade, RD; Owen, R; Sanchez, R; Vieta, E, 2010)	0.36
"Long-term aripiprazole adjunctive to lithium/valproate in bipolar mania was safe and well tolerated."	( Assessment of safety, tolerability and effectiveness of adjunctive aripiprazole to lithium/valproate in bipolar mania: a 46-week, open-label extension following a 6-week double-blind study. Baudelet, C; Marcus, RN; McQuade, RD; Owen, R; Sanchez, R; Vieta, E, 2010)	0.36
" An understanding of structure-activity relationships (SARs) of chemicals can make a significant contribution to the identification of potential toxic effects early in the drug development process and aid in avoiding such problems."	( Developing structure-activity relationships for the prediction of hepatotoxicity. Fisk, L; Greene, N; Naven, RT; Note, RR; Patel, ML; Pelletier, DJ, 2010)	0.36
" We conclude that valproic acid+ATRA+theophylline combined with 6-mercaptopurin or hydroxyurea can be safe and effective in palliative treatment of human AML."	( Combination of the histone deacetylase inhibitor valproic acid with oral hydroxyurea or 6-mercaptopurin can be safe and effective in patients with advanced acute myeloid leukaemia--a report of five cases. Bruserud, Ø; Fredly, H; Gjertsen, BT; Stapnes Bjørnsen, C, 2010)	0.95
" In the early phase of treatment, the main adverse effects included drowsiness, dizziness, and anorexia."	( A 6-month prospective study on efficacy safety and QOL profiles of extended-release formulation of valproate in patients with epilepsy. Hong, Z; Li, T; Wang, B; Wu, XY; Xu, L; Yu, PM; Yue, L; Zhu, GX, 2011)	0.37
"Antiepileptic drugs (AED) as transplacental agents are known to have adverse effects on fetal development."	( Transplacental genotoxicity of antiepileptic drugs: animal model and pilot study on mother/newborn cohort. Bakulic, TI; Demarin, V; Fucic, A; Gjergja, R; Jazbec, AM; Katic, J; Markovic, D; Miškov, S; Stojković, R; Zeljezic, D, 2010)	0.36
"Numerous xenobiotics are toxic to human and animal cells by interacting with their metabolism, but the precise metabolic step affected and the biochemical mechanism behind such a toxicity often remain unknown."	( Protocols and applications of cellular metabolomics in safety studies using precision-cut tissue slices and carbon 13 NMR. Baverel, G; Duplany, A; El Hage, M; Faiz, H; Ferrier, B; Gauthier, C; Martin, G; Renault, S, 2011)	0.37
"It has been reported that urinary excretion of two metabolites of valproic acid (VPA), 4-ene-valproic acid (4-VPA)and 2,4-diene-valproic acid (2,4-VPA), increased exponentially with the administration of high doses of VPA, and this increased formation of toxic metabolites could be related to VPA hepatotoxicity in humans."	( Dose-dependent pharmacokinetics of toxic metabolites is not related to increased toxicity following high-dose valproic acid in rats. Jung, BH; Kim, BJ; Lee, JH; Lee, MS; Lee, YJ; Oh, JH, 2010)	0.81
" In many situations, the final choice of an antiepileptic drug may need a change due to the agent's side-effect profile."	( Cerebellar atrophy in a child with valproate toxicity. Bhatt, S; Ghosh, VB; Kapoor, S; Prakash, A, 2011)	0.37
"Depakote-induced hepatotoxicity has been well established as an adverse effect, and periodic monitoring of drug level is often required."	( Thinking beyond the obvious: hepatotoxicity secondary to idiosyncratic depakote toxicity. Asadi, S; Avashia, KD; Chaudrey, KH; Ihsan, M; Irshad Khan, SI; Naser, TB; Nouri-Kolouri, M; Steinberg, A, 2012)	0.38
" Our work showed that adverse effects in epileptics under high doses of AVP was related to the association of the AVP with other antiepileptic in particular carbamazépine, phenobarbital and benzodiazepines rather than supra-therapeutic plasmatic concentrations of AVP."	( [Relationship between plasma concentrations of valproic acid and hepatotoxicity in patients receiving high doses]. Atheymen, R; Ben Mahmoud, L; Ghozzi, H; Hakim, A; Hammami, S; Sahnoun, Z; Zeghal, K, )	0.39
"To evaluate the efficacy and adverse effect of valproic acid (VPA) in combination with low dose chemotherapy on intermediate and high-risk myelodysplastic syndrome."	( [The efficacy and safety of valproic acid in combination with low dose chemotherapy on intermediate and high-risk myelodysplastic syndrome]. Ge, GM; Han, XL; He, LS; Huang, Y; Wu, S; Yan, YP; Zhang, QY, 2011)	0.92
" The outcome and adverse effect were recorded after the treatment."	( [The efficacy and safety of valproic acid in combination with low dose chemotherapy on intermediate and high-risk myelodysplastic syndrome]. Ge, GM; Han, XL; He, LS; Huang, Y; Wu, S; Yan, YP; Zhang, QY, 2011)	0.66
" The adverse effect of the low dose chemotherapy in combination with VPA regimen was tolerated."	( [The efficacy and safety of valproic acid in combination with low dose chemotherapy on intermediate and high-risk myelodysplastic syndrome]. Ge, GM; Han, XL; He, LS; Huang, Y; Wu, S; Yan, YP; Zhang, QY, 2011)	0.66
"With acceptable adverse effect, the low dose chemotherapy in combination with VPA regimen is effective for the treatment of intermediate and high-risk myelodysplastic syndrome."	( [The efficacy and safety of valproic acid in combination with low dose chemotherapy on intermediate and high-risk myelodysplastic syndrome]. Ge, GM; Han, XL; He, LS; Huang, Y; Wu, S; Yan, YP; Zhang, QY, 2011)	0.66
" Plasma concentrations (pc), interactions between drugs in the ICU context, adverse effects and seizure occurrences were observed and recorded."	( Levetiracetam compared to valproic acid: plasma concentration levels, adverse effects and interactions in aneurysmal subarachnoid hemorrhage. Bjeljac, M; Keller, E; Mink, S; Muroi, C; Seule, M, 2011)	0.67
" There was no statistical significance among treatment arms in remission rates, secondary outcome measures, and adverse events."	( A pilot study of the efficacy and safety of paroxetine augmented with risperidone, valproate, buspirone, trazodone, or thyroid hormone in adult Chinese patients with treatment-resistant major depression. Calabrese, JR; Cao, L; Chen, J; Cui, X; Fang, Y; Gao, K; Hong, W; Jiang, K; Wang, Y; Wu, Z; Xu, Y; Yi, Z; Yuan, C, 2011)	0.37
"In recent years, phenobarbital, as an antiepileptic drug, has become less popular based on adverse events, especially cognitive and behavioural side effects."	( Side effects of phenobarbital in epilepsy: a systematic review. Li, YP; Zeng, LN; Zhang, LL, 2011)	0.37
" The determination of adverse effects of combined antiepileptic drugs (AEDs) from different studies was complicated by numerous factors including study design, different descriptions of adverse events and a lack of standardised data collection."	( Side effects of phenobarbital in epilepsy: a systematic review. Li, YP; Zeng, LN; Zhang, LL, 2011)	0.37
"Phenobarbital was associated with a higher rate of drug withdrawal although there was no evidence to suggest that phenobarbital caused more adverse events compared to carbamazepine, valproic acid or phenytoin."	( Side effects of phenobarbital in epilepsy: a systematic review. Li, YP; Zeng, LN; Zhang, LL, 2011)	0.56
" We conclude that long-term treatment with VPA is safe in HAM/TSP."	( Safety of long-term treatment of HAM/TSP patients with valproic acid. Asquith, B; Bangham, C; Belrose, G; Boxus, M; Césaire, R; Gillet, N; Lezin, A; Olindo, S; Rodriguez, S; Signaté, A; Smadja, D; Verlaeten, O; Willems, L, 2011)	0.62
" Hence intravenous valproate is safe and efficacious, with less time to regain consciousness."	( Comparative efficacy and safety of intravenous valproate and phenytoin in children. Aggarwal, A; Mittal, H; Rai, A; Sharma, S, 2011)	0.37
" However, long-term VPA treatment has several adverse effects on the reproductive system."	( Investigation on sodium valproate induced germ cell damage, oxidative stress and genotoxicity in male Swiss mice. Ahmad, T; Jena, G; Khan, S; Kushwaha, S; Parekh, CV; Trivedi, PP, 2011)	0.37
" Although there are many reports of adverse effects of VPA, studies focusing on the concentration-response relationships of VPA and its metabolites in patients with epilepsy are extremely limited."	( Simultaneous determination of valproic acid and 2-propyl-4-pentenoic acid for the prediction of clinical adverse effects in Chinese patients with epilepsy. Chen, SD; Chen, ZJ; Fang, ZY; Huang, M; Li, JL; Shu, WY; Wang, HS; Wang, XD; Zhang, Y; Zhou, JQ; Zhou, LM, 2012)	0.67
" However, these medications have several well-known adverse effects."	( Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial. Ashrafi, MR; Bavarian, B; Ghaempanah, M; Khosroshahi, N; Malamiri, RA; Nikkhah, A, 2012)	0.38
" We finally concluded that VPA hepatotoxicity is a result of metabolic activation by CYP2E1 and ROS formation, leading to lysosomal labialization, mitochondrial/lysosomal toxic cross-talk and finally general cellular proteolysis in the rat hepatocytes."	( A new approach on valproic acid induced hepatotoxicity: involvement of lysosomal membrane leakiness and cellular proteolysis. Eskandari, MR; Fard, JK; Kaghazi, A; Pourahmad, J; Shahraki, J; Shaki, F, 2012)	0.71
" Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, weight, and extrapyramidal symptoms (EPSs)."	( Safety and efficacy of olanzapine monotherapy and olanzapine with a mood stabilizer in 18-week treatment of manic/mixed episodes for Japanese patients with bipolar I disorder. Higuchi, T; Kanba, S; Katagiri, H; Takahashi, M; Takita, Y; Tohen, M, 2012)	0.38
"There were no deaths or serious adverse events considered potentially related to olanzapine in the monotherapy group (N = 100) or the combination-therapy group (N = 39)."	( Safety and efficacy of olanzapine monotherapy and olanzapine with a mood stabilizer in 18-week treatment of manic/mixed episodes for Japanese patients with bipolar I disorder. Higuchi, T; Kanba, S; Katagiri, H; Takahashi, M; Takita, Y; Tohen, M, 2012)	0.38
"Individuals treated with combined valproate-lamotrigine rarely present late adverse effects (unrelated to introduction and titration)."	( Late adverse effects of the coadministration of valproate and lamotrigine. Moreira, B; Thome-Souza, S; Valente, KD, 2012)	0.38
" VPA was well tolerated and only 47 people reported adverse events which were mostly mild."	( Sodium valproate for epilepsy in rural China: an efficacy and safety assessment in primary care. Li, S; Ru, X; Sander, JW; Wang, W; Wu, J; Zheng, J; Zhu, S, 2012)	0.38
" Rash was the major side effect for withdrawal."	( [Efficacy and safety of the combined therapy of valproic acid and lamotrigine for epileptics]. Hu, Q; Kang, HC; Li, X; Liu, XY; Liu, ZG; Wang, M; Xu, F; Zeng, Z; Zhu, SQ, 2012)	0.63
"The co-medication of VPA and LTG is both effective and safe for all epileptic types, especially for SPS and GS."	( [Efficacy and safety of the combined therapy of valproic acid and lamotrigine for epileptics]. Hu, Q; Kang, HC; Li, X; Liu, XY; Liu, ZG; Wang, M; Xu, F; Zeng, Z; Zhu, SQ, 2012)	0.63
" Adverse events were reported in 41% of the patients of which fatigue was most frequent (24%)."	( Rufinamide in children with refractory epilepsy: pharmacokinetics, efficacy, and safety. Dahlin, MG; Ohman, I, 2012)	0.38
" VPA is a relatively safe drug, but its use in higher concentrations is associated with idiosyncratic neurotoxicity."	( An in vitro approach to assess the neurotoxicity of valproic acid-induced oxidative stress in cerebellum and cerebral cortex of young rats. Chaudhary, S; Parvez, S, 2012)	0.63
"Since all the latter test compounds, like many toxic compounds, negatively interact with cellular metabolic pathways, we also illustrate our biochemical toxicology approach in which we used not only enzymatic but also carbon 13 NMR measurements and mathematical modelling of metabolic pathways."	( Use of precision-cut renal cortical slices in nephrotoxicity studies. Baverel, G; Duplany, A; El Hage, M; Ferrier, B; Gauthier, C; Knouzy, B; Martin, G, 2013)	0.39
"VPA plays a complex role in patients with pigmentary retinal dystrophies and may be associated with VA and field decline as well as adverse side effects."	( Long-term follow-up for efficacy and safety of treatment of retinitis pigmentosa with valproic acid. Bhalla, S; Bhullar, S; Joshi, D; Kasuga, D; Kay, CN; Park, Y, 2013)	0.61
" We chose the number of patients experiencing = 50% reduction in pain and number of patient withdrawals due to adverse events (AE) as primary outcomes for efficacy and safety, respectively."	( Comparative efficacy and safety of six antidepressants and anticonvulsants in painful diabetic neuropathy: a network meta-analysis. Bansal, D; Bhansali, A; Ghai, B; Gudala, K; Hota, D; Rudroju, N; Talakokkula, ST, )	0.13
"Gabapentin was found to be most efficacious and amitriptyline to be least safe among the treatments included in the study."	( Comparative efficacy and safety of six antidepressants and anticonvulsants in painful diabetic neuropathy: a network meta-analysis. Bansal, D; Bhansali, A; Ghai, B; Gudala, K; Hota, D; Rudroju, N; Talakokkula, ST, )	0.13
" Hepatotoxicity is a rare but serious side effect resulting from its use, particularly in young patients."	( Evidence for a potential protective effect of carnitine-pantothenic acid co-treatment on valproic acid-induced hepatotoxicity. Felker, D; Johnson, DE; Lynn, A; Wang, S, 2014)	0.62
" Safety studies of intravenous VPA administration in patients with SE showed a low incidence of adverse events overall (<10%), mainly dizziness, thrombocytopenia, and mild hypotension, which was independent of infusion rates."	( Efficacy and safety of intravenous valproate for status epilepticus: a systematic review. Brigo, F; Höfler, J; Trinka, E; Zerbs, A, 2014)	0.4
"The published experience is consistent with VPA being a safe and effective therapeutic option for patients with established SE who have previously failed conventional first-line treatment with benzodiazepines, but high-quality randomized controlled trials are needed to inform clinicians on its comparative effectiveness in SE."	( Efficacy and safety of intravenous valproate for status epilepticus: a systematic review. Brigo, F; Höfler, J; Trinka, E; Zerbs, A, 2014)	0.4
" However, a complete reversal of encephalopathy, on withdrawal of the drug, strongly suggested an adverse drug reaction (ADR) due to valproic acid."	( Encephalopathy in an infant with infantile spasms: possible role of valproate toxicity. Sampath, S; Sivathanu, S; Sunderkumar, S; Veerasamy, M, 2014)	0.61
" The toxicity assay on primary cultures of astrocytes indicated that the synthetized conjugate was less toxic than both free VPA and L-Phenylalanine."	( N-valproyl-L-phenylalanine as new potential antiepileptic drug: synthesis, characterization and in vitro studies on stability, toxicity and anticonvulsant efficacy. Avellone, G; Carafa, M; Carletti, F; De Caro, V; Ferrantelli, E; Giannola, LI; Rizzo, V; Sardo, P; Scaturro, AL; Schiera, G; Sutera, FM, 2014)	0.4
"The authors discuss adverse events which are often missed but clinicians should pay attention to in order to preserve patients'quality of life(QOL)."	( [Adverse events of psychotropic drugs]. Kikuchi, T; Watanabe, K, 2014)	0.4
" Our data suggest that valproate has adverse effects on renal tubular functions."	( Does nephrotoxicity exist in pediatric epileptic patients on valproate or carbamazepine therapy? Buyan, N; Demir, E; Gücüyener, K; Gülbahar, Ö; Gürkaş, E; Havali, C; Serdaroğlu, A; Yılmaz, Ü, 2015)	0.42
" Taking all together, this demo-case study showed that inclusion of multiple-endpoints in ZET may increase the sensitivity of the assay, contribute to the elucidation of the mode of toxic action and to a better definition of the applicability domain of ZET."	( Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs. Beker van Woudenberg, A; Bouma, M; de Groot, D; Hermsen, S; Menke, A; Piersma, A; Rijkmans, E; Snel, C; Wolterbeek, A, 2014)	0.4
" In a comparative study, in situ generated diclofenac glucuronide was not toxic to rat hepatocytes, as assessed using the same chemical modulators, thereby demonstrating the utility of the sandwich-cultured rat hepatocyte model."	( Evaluation of in situ generated valproyl 1-O-β-acyl glucuronide in valproic acid toxicity in sandwich-cultured rat hepatocytes. Abbott, FS; Chang, TK; Surendradoss, J, 2014)	0.64
" Hepatotoxicity is a rare and potentially fatal adverse reaction for this medicine."	( Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase. Choonara, I; Edwards, IR; Star, K, 2014)	1.85
" Polytherapy is commonly reported and seems to be a risk factor for hepatotoxicity, pancreatitis and other serious adverse drug reactions with valproic acid."	( Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase. Choonara, I; Edwards, IR; Star, K, 2014)	2.05
" Previous studies have reported an increased generation of reactive oxygen species and oxidative stress in the toxic mechanism of VPA."	( Edaravone ameliorates the adverse effects of valproic acid toxicity in small intestine. Alev, B; Emekli-Alturfan, E; Koc-Ozturk, L; Oktay, S; Tunali, S; Tunali-Akbay, T; Yanardag, R; Yarat, A, 2015)	0.68
" Haematological toxicity is a limiting side effect of both, first line radio-chemotherapy with temozolomide (TMZ) and co-medication with antiepileptic drugs."	( Haematological toxicity of Valproic acid compared to Levetiracetam in patients with glioblastoma multiforme undergoing concomitant radio-chemotherapy: a retrospective cohort study. Geroldinger, A; Gleiss, A; Grisold, W; Marosi, C; Moser, W; Oberndorfer, S; Sax, C; Sherif, C; Tinchon, A, 2015)	0.71
"Weight gain and alopecia were the most common patient-reported CSEs in this study, and weight gain was the most likely cosmetic side effect to result in dosage adjustment or medication discontinuation."	( Cosmetic side effects of antiepileptic drugs in adults with epilepsy. Buchsbaum, R; Chen, B; Choi, H; Detyniecki, K; Hirsch, LJ; Javed, A; Kato, K; Legge, A; Moeller, J, 2015)	0.42
" Twenty-two patients experienced stiripentol-related adverse events, with two having severe ones."	( Long-term safety and efficacy of stiripentol for the treatment of Dravet syndrome: A multicenter, open-label study in Japan. Inoue, Y; Ohtsuka, Y, 2015)	0.42
"During adjunctive stiripentol use with clobazam and valproate, careful monitoring for adverse events such as somnolence and loss of appetite is recommended, and dose reduction may become needed for any of the antiepileptics."	( Long-term safety and efficacy of stiripentol for the treatment of Dravet syndrome: A multicenter, open-label study in Japan. Inoue, Y; Ohtsuka, Y, 2015)	0.42
" This systematic review aimed to assess the prevalence of their adverse effects (AEs) and to provide recommendations on their clinical management."	( Management of adverse effects of mood stabilizers. Hidalgo, D; León-Caballero, J; Murru, A; Pacchiarotti, I; Popovic, D; Vieta, E, 2015)	0.42
" Treatment-emergent adverse events occurred in 82% (CBZ/OXC), 76% (LTG), 73% (LEV), and 67% (VPA) of patients; most were of mild-to-moderate intensity."	( Efficacy and safety of ezogabine/retigabine as adjunctive therapy to specified single antiepileptic medications in an open-label study of adults with partial-onset seizures. Brandt, C; Daniluk, J; DeRossett, S; Edwards, S; Lerche, H; Lotay, N, 2015)	0.42
" The model predicts that bosentan is safe at the considered dose under the assumed conditions upon 4 weeks exposure."	( In Silico Modeling for the Prediction of Dose and Pathway-Related Adverse Effects in Humans From In Vitro Repeated-Dose Studies. Bucher, J; Heinzle, E; Klein, S; Maggioni, S; Mauch, K; Mueller, D; Niklas, J; Noor, F; Shevchenko, V, 2016)	0.43
"The objective was to determine whether sex and age are associated with short-term headache relief, sustained headache freedom, or adverse medication effects in data collected during 3 emergency department (ED)-based acute migraine comparative efficacy trials."	( Age But Not Sex Is Associated With Efficacy and Adverse Events Following Administration of Intravenous Migraine Medication: An Analysis of a Clinical Trial Database. Bijur, PE; Cisewski, DH; Friedman, BW; Gallagher, EJ; Holden, L, )	0.13
" In each of these studies, (1) short-term efficacy (patient description of the headache as "mild" or "none" 1 hour after medication administration); (2) sustained efficacy (patient description of the headache as "none" within 2 hours of medication administration and no headache recurrence for 24 hours post ED discharge); and (3) the frequency of any adverse medication effects within 24 hours of medication administration was determined."	( Age But Not Sex Is Associated With Efficacy and Adverse Events Following Administration of Intravenous Migraine Medication: An Analysis of a Clinical Trial Database. Bijur, PE; Cisewski, DH; Friedman, BW; Gallagher, EJ; Holden, L, )	0.13
" Age was associated with both efficacy and adverse events."	( Age But Not Sex Is Associated With Efficacy and Adverse Events Following Administration of Intravenous Migraine Medication: An Analysis of a Clinical Trial Database. Bijur, PE; Cisewski, DH; Friedman, BW; Gallagher, EJ; Holden, L, )	0.13
"In patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment."	( Specific adverse effects of antiepileptic drugs--A true-to-life monotherapy study. Fidzinski, P; Gaus, V; Holtkamp, M; Kowski, AB; Losch, F; Weissinger, F, 2016)	0.43
"All patients ≥16years of age with epilepsy for ≥12months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment."	( Specific adverse effects of antiepileptic drugs--A true-to-life monotherapy study. Fidzinski, P; Gaus, V; Holtkamp, M; Kowski, AB; Losch, F; Weissinger, F, 2016)	0.43
" Major adverse effects included dizziness and loss of appetite."	( Safety and efficacy of valproic acid treatment in SCA3/MJD patients. Chuang, DM; Jiang, H; Lei, LF; Song, WH; Tang, BS; Wang, JL; Yang, GP, 2016)	0.74
" Safety (primary outcome) was assessed by incidence of treatment emergent adverse events (AEs)."	( Safety and effectiveness of divalproex sodium extended release containing regimen in Indian patients with bipolar I disorder in continuation phase: Results of EASED registry. Chaudhuri, U; Mohanasundaram, S; Reddy, MS; Shah, N; Vohra, S, 2016)	0.43
"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
" One of the most dangerous adverse effects of LTG is skin rash, which can make early cessation necessary."	( Safety of Long-term Use of Lamotrigine for the Treatment of Psychiatric Disorders. Fujito, H; Inaba, T; Kawashima, T; Matsushima, J; Mizoguchi, Y; Mochinaga, S; Monji, A; Sogawa, R, )	0.13
" Patients were retrospectively divided into those who discontinued treatment within 6 months and those who continued for longer, and the groups were compared for adverse effects."	( Safety of Long-term Use of Lamotrigine for the Treatment of Psychiatric Disorders. Fujito, H; Inaba, T; Kawashima, T; Matsushima, J; Mizoguchi, Y; Mochinaga, S; Monji, A; Sogawa, R, )	0.13
" Of the patients who continued treatment for 6 months or longer, only 2 later discontinued treatment because of adverse effects."	( Safety of Long-term Use of Lamotrigine for the Treatment of Psychiatric Disorders. Fujito, H; Inaba, T; Kawashima, T; Matsushima, J; Mizoguchi, Y; Mochinaga, S; Monji, A; Sogawa, R, )	0.13
"Clinicians must be mindful of the adverse effects occurring early during the titration phase."	( Safety of Long-term Use of Lamotrigine for the Treatment of Psychiatric Disorders. Fujito, H; Inaba, T; Kawashima, T; Matsushima, J; Mizoguchi, Y; Mochinaga, S; Monji, A; Sogawa, R, )	0.13
"Background The impact of adverse events (AEs) of antiepileptic drugs (AEDs) have an impact on compliance and dropouts."	( Antiepileptic drugs in migraine and epilepsy: Who is at increased risk of adverse events? Bedetti, C; Calabresi, P; Caproni, S; Corbelli, I; Costa, C; Cupini, LM; Eusebi, P; Romoli, M; Sarchielli, P; Siliquini, S, 2018)	0.48
" Summary effect for migraine headache days, headache frequency, at least 50% reduction in headache attacks, all-adverse events, nausea, somnolence, dizziness, withdrawal and withdrawal due to adverse events were produced by synthesizing both direct and indirect evidence."	( Unveiling the relative efficacy, safety and tolerability of prophylactic medications for migraine: pairwise and network-meta analysis. He, A; Li, C; Song, D; Zhang, L, 2017)	0.46
" While the concentration of 4-ene-VPA was not suitable as an early warning index, the results provide clear theoretical guidance for the rational and safe clinical use of VPA."	( Association of CYP2C9, CYP2A6, ACSM2A, and CPT1A gene polymorphisms with adverse effects of valproic acid in Chinese patients with epilepsy. Ma, HY; Pan, J; Wang, C; Wang, P; Yang, LP; Yang, X, 2017)	0.68
" Hyperammonemic coma is determined through a complicated differential diagnosis, and although it can also be induced as a side effect of valproate (VPA), this cause is frequently unrecognized or confused with upper gastrointestinal hemorrhage (UGH)-induced hepatic encephalopathy."	( Hyperammonemic coma after craniotomy: Hepatic encephalopathy from upper gastrointestinal hemorrhage or valproate side effect?: Case report and literature review. Gao, L; Guo, X; Wei, J; Xing, B; Xu, Z, 2017)	0.46
" However, whether it origins from upper gastrointestinal hemorrhage or valproate side effect is uncertain."	( Hyperammonemic coma after craniotomy: Hepatic encephalopathy from upper gastrointestinal hemorrhage or valproate side effect?: Case report and literature review. Gao, L; Guo, X; Wei, J; Xing, B; Xu, Z, 2017)	0.46
"These results suggest that epigenetic changes at the striatal Drd2 promoter drive age-related increases in antipsychotic side effect susceptibility, and HDAC inhibitors may be an effective adjunct treatment strategy to reduce side effects in aged populations."	( Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice. Csernansky, JG; Dong, H; Fang, D; Fisher, DW; Montalvo-Ortiz, JL; Rodríguez, G, 2017)	0.46
" Patients were monitored for adverse events and data were collected for pharmacokinetic, pharmacodynamic, and safety profiling of valproic acid."	( Safety and Tolerability of Intravenous Valproic Acid in Healthy Subjects: A Phase I Dose-Escalation Trial. Alam, HB; Bonham, T; Georgoff, PE; Halaweish, I; Luo, R; Nikolian, VC; Pai, MP; Parameswaran, A; Sun, D; Tafatia, C; To, K; Watcharotone, K, 2018)	0.95
" The most common adverse events were hypoacusis (n = 19), chills (n = 18), and headache (n = 16)."	( Safety and Tolerability of Intravenous Valproic Acid in Healthy Subjects: A Phase I Dose-Escalation Trial. Alam, HB; Bonham, T; Georgoff, PE; Halaweish, I; Luo, R; Nikolian, VC; Pai, MP; Parameswaran, A; Sun, D; Tafatia, C; To, K; Watcharotone, K, 2018)	0.75
"Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control."	( Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis. Cogo, E; D'Souza, J; Finkelstein, Y; Hemmelgarn, BR; Hutton, B; Kealey, R; MacDonald, H; Reynen, E; Rios, P; Soobiah, C; Straus, SE; Thavorn, K; Tricco, AC; Veroniki, AA; Yazdi, F, 2017)	0.46
"The liver toxicity of valproic acid (VPA) is an established side effect of this widely used antiepileptic drug, which is extremely problematic for patients with metabolic epilepsy and particularly epilepsy due to mitochondrial dysfunction."	( Mitochondrial Liver Toxicity of Valproic Acid and Its Acid Derivatives Is Related to Inhibition of α-Lipoamide Dehydrogenase. Bialer, M; Eisenkraft, A; Elger, CE; Kudin, AP; Kunz, WS; Mawasi, H, 2017)	1.05
" Furthermore, VPA modulated the expression and DNA methylation level of nuclear receptors and their target genes involved in the adverse outcome pathway of steatosis, thereby expanding our current knowledge of the pathway."	( Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Claessen, SMH; de Kok, TMCM; Jennen, DGJ; Kleinjans, JCS; Theunissen, DHJ; van Breda, SGJ; van Herwijnen, M, 2018)	0.72
"This study aims to describe the incidence of adverse drug reactions (ADRs) in children receiving antiepileptic drugs (AEDs) and compare ADRs to the individual drugs when given as monotherapy."	( Safety of antiepileptic drugs in children and young people: A prospective cohort study. Choonara, I; Egunsola, O; Sammons, HM; Whitehouse, WP, 2018)	0.48
" Adverse reactions to antiepileptic drugs (AEDs) were elicited at the time of enrolment and after 3 months using the Paediatric Epilepsy Side Effects Questionnaire."	( Safety of antiepileptic drugs in children and young people: A prospective cohort study. Choonara, I; Egunsola, O; Sammons, HM; Whitehouse, WP, 2018)	0.48
"Renal injury is a hallmark adverse reaction to sodium valproate (SVP), and caffeic acid (CAFF) is a phenolic compound that has anti-inflammatory and antioxsidant properties."	( Study on the influence of caffeic acid against sodium valproate-induced nephrotoxicity in rats. Gad, AM, 2018)	0.48
" Later it became apparent that the patient had toxic unbound valproic acid levels due to hypoalbuminaemia and impaired renal function."	( [Valproic acid toxicity due to misinterpretation of plasma levels: increase in unbound fraction caused by hypoalbuminaemia and renal dysfunction]. Dols, A; Jacobs, GE; Nauta, KJ; Ruiter-Visser, R; Smulders, YM, 2018)	1.63
" Clinical data on epilepsy, characteristics of VPA treatment, risk factors for VHT, laboratory data on liver and pancreas functions, and adverse effects were collected."	( Variants p.Q1236H and p.E1143G in mitochondrial DNA polymerase gamma POLG1 are not associated with increased risk for valproate-induced hepatotoxicity or pancreatic toxicity: A retrospective cohort study of patients with epilepsy. Ansakorpi, H; Eriksson, K; Haapala, P; Haataja, L; Hinttala, R; Hynynen, J; Jyrkilä, A; Kälviäinen, R; Kärppä, M; Komulainen-Ebrahim, J; Lähdetie, J; Majamaa, K; Mäkitalo, A; Myllynen, P; Pokka, T; Pylvänen, L; Rantala, H; Sokka, A; Uusimaa, J; Vieira, P; Ylikotila, P, 2018)	0.48
" In children under 2 years old, serious adverse effects are appear to be more frequent."	( Adverse Effects of Treatment with Valproic Acid during the Neonatal Period. Baudou, E; Benevent, J; Hachon LeCamus, C; Montastruc, JL; Touati, G, 2019)	0.79
"The aim of our study is to report the adverse effects observed in a population of full-term newborns treated with VPA."	( Adverse Effects of Treatment with Valproic Acid during the Neonatal Period. Baudou, E; Benevent, J; Hachon LeCamus, C; Montastruc, JL; Touati, G, 2019)	0.79
"For 5 of the 123 newborns treated with VPA, treatment had to be discontinued due to adverse effects."	( Adverse Effects of Treatment with Valproic Acid during the Neonatal Period. Baudou, E; Benevent, J; Hachon LeCamus, C; Montastruc, JL; Touati, G, 2019)	0.79
"While the serious adverse effects of VPA noted were all reversible with the discontinuation of the treatment, the occurrence of encephalopathies with hyperammoniemia is a serious complication that is potentially lethal and calls for close clinical monitoring of newborns treated with valproate."	( Adverse Effects of Treatment with Valproic Acid during the Neonatal Period. Baudou, E; Benevent, J; Hachon LeCamus, C; Montastruc, JL; Touati, G, 2019)	0.79
" Diaries of seizure frequency and adverse events were reviewed at each visit."	( Long-Term Safety, Tolerability, and Efficacy of Cannabidiol in Children with Refractory Epilepsy: Results from an Expanded Access Program in the US. Caminha Nunes, E; Cilio, MR; Oldham, MS; Rahdari, S; Sands, TT; Tilton, N, 2019)	0.51
" Adverse events were reported in 21 patients (80."	( Long-Term Safety, Tolerability, and Efficacy of Cannabidiol in Children with Refractory Epilepsy: Results from an Expanded Access Program in the US. Caminha Nunes, E; Cilio, MR; Oldham, MS; Rahdari, S; Sands, TT; Tilton, N, 2019)	0.51
"8% had adverse events, including 23."	( Long-Term Safety, Tolerability, and Efficacy of Cannabidiol in Children with Refractory Epilepsy: Results from an Expanded Access Program in the US. Caminha Nunes, E; Cilio, MR; Oldham, MS; Rahdari, S; Sands, TT; Tilton, N, 2019)	0.51
" Sodium Valproate, renowned to be a potent antiepileptic drug, when taken in overdose may cause toxic effects to liver and other organs as well."	( Differential Hepatotoxic Effects of Sodium Valproate at Different Doses in Albino Rats. Gupta, PK; Hoque, MK; Sapkota, AS; Shakya, R, )	0.13
" The secondary outcome was the safety of VPA in terms of reported adverse effects."	( Efficacy and Safety of Valproic Acid for Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis. Abo-Elghar, H; Doheim, MF; ELdoadoa, MF; Elshafay, A; Hieu, TH; Hirayama, K; Holloway, SK; Huy, NT; Kassem, MAM, 2019)	0.82
" Regarding the safety of the treatment, a double-blind, randomized, placebo-controlled trial reported no statistically significant differences for adverse events (AEs) between groups."	( Efficacy and Safety of Valproic Acid for Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis. Abo-Elghar, H; Doheim, MF; ELdoadoa, MF; Elshafay, A; Hieu, TH; Hirayama, K; Holloway, SK; Huy, NT; Kassem, MAM, 2019)	0.82
" Furthermore, VPA appears to be a relatively safe drug, although treatment may be associated with a wide range of AEs (including body weight increase, fatigue, fever, flu-like symptoms, irritability, and pain)."	( Efficacy and Safety of Valproic Acid for Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis. Abo-Elghar, H; Doheim, MF; ELdoadoa, MF; Elshafay, A; Hieu, TH; Hirayama, K; Holloway, SK; Huy, NT; Kassem, MAM, 2019)	0.82
" Furthermore, it was possible to discriminate toxicants acting at different time points during embryonic development and, therefore, responsible for distinct adverse effects on neural tube formation."	( Accuracy, discriminative properties and reliability of a human ESC-based in vitro toxicity assay to distinguish teratogens responsible for neural tube defects. De Geyter, C; Feutz, AC, 2019)	0.51
"The adverse drug reactions (ADRs) related to clonazepam are mild, and only two cases of myotoxicity induced by clonazepam have been reported, with both patients recovering well."	( A serious adverse drug reaction probably induced by clonazepam: a case report of myotoxicity. Han, X; Wang, J, 2019)	0.51
"Our case adds to the existing literature by demonstrating that patients may experience adverse medication effects despite lamotrigine levels that are normally considered to be in the therapeutic range, highlighting the importance of clinical correlation when obtaining medication levels."	( Delirium Secondary to Lamotrigine Toxicity. Catalano, G; Catalano, MC; Fusick, AJ; Gunther, SR; Hernandez, MJ; Sanchez, DL; Sullivan, GA, 2020)	0.56
" Indeed, there were no significant differences found in the scores of Mini-mental State Examination, Cohen-Mansfield Agitation Inventory and number of patients with adverse events."	( Efficacy and safety of valproic acid in dementia: A systematic review with meta-analysis. Liu, J; Wang, LN, )	0.44
" We conclude that the PluriBeat assay is a novel method for predicting chemicals' adverse effects on embryonic development."	( A novel human pluripotent stem cell-based assay to predict developmental toxicity. Emnéus, JK; Holst, B; Lauschke, K; Meiser, I; Neubauer, JC; Rasmussen, MA; Rosenmai, AK; Schmidt, K; Taxvig, C; Vinggaard, AM, 2020)	0.56
" However, the free form of VPA is responsible for its pharmacologic and toxic effects, and the total and free concentrations are highly discordant because of VPA's highly protein bound and saturable binding characteristics."	( Safety range of free valproic acid serum concentration in adult patients. Huang, SY; Kuo, CH; Tseng, YJ; Wang, CY; Wang, KC; Wu, CC, 2020)	0.88
" Patient characteristics, VPA use, and adverse effects (thrombocytopenia, hyperammonemia, and hepatotoxicity) were recorded."	( Safety range of free valproic acid serum concentration in adult patients. Huang, SY; Kuo, CH; Tseng, YJ; Wang, CY; Wang, KC; Wu, CC, 2020)	0.88
" The aim of this study is to investigate the potential toxic effect of aspartic acid-coated magnesium oxide nanoparticles (Mg nano) and valproate (valp) using an in vitro three-dimensional (3D) human liver organoid model and an in vivo pentylenetetrazole (PTZ)-induced convulsion model in rats."	( The potential toxic effects of magnesium oxide nanoparticles and valproate on liver tissue. Ahmed-Farid, OA; Alzebdeh, D; Atala, A; Bishop, C; Diab, AEA; Mekky, G; Seeds, M; Shehata, AM, 2021)	0.62
" However, women must balance the benefit of treatment against all possible adverse effects."	( Active Surveillance of the Safety of Medications Used During Pregnancy. Bateman, BT; Hernández-Díaz, S; Huybrechts, KF; Kulldorff, M; Mogun, H; Wang, SV; Zhu, Y, 2021)	0.62
" VPA has been reported to be associated with many adverse effects, including hepatotoxicity."	( Protective effects of naringin on valproic acid-induced hepatotoxicity in rats. Ates, B; Colak, C; Gunata, M; Koroglu, OF; Parlakpinar, H; Tanriverdi, LH; Vardi, N; Yildiz, A, 2021)	0.9
"We systematically reviewed the existing literature on the cosmetic adverse effects of antiseizure medications (ASMs) in order to depict a clear picture of these unwanted side effects of ASMs with a particular attention to hair loss, hirsutism, acne, and gingival hyperplasia."	( Cosmetic adverse effects of antiseizure medications; A systematic review. Asadi-Pooya, AA; Mirzaei Damabi, N; Rostaminejad, M; Zeraatpisheh, Z, 2021)	0.62
" The most robust evidence on cosmetic adverse effects of ASMs were related to phenytoin (causing gingival hyperplasia, hirsutism, and acne) and valproate (causing hair loss and hirsutism); however, many other ASMs were also implicated in causing these cosmetic adverse effects."	( Cosmetic adverse effects of antiseizure medications; A systematic review. Asadi-Pooya, AA; Mirzaei Damabi, N; Rostaminejad, M; Zeraatpisheh, Z, 2021)	0.62
"Antiseizure medications may be associated with various cosmetic adverse effects."	( Cosmetic adverse effects of antiseizure medications; A systematic review. Asadi-Pooya, AA; Mirzaei Damabi, N; Rostaminejad, M; Zeraatpisheh, Z, 2021)	0.62
" Perturbations of these endpoints are described as common key events in adverse outcome pathways (AOPs) specific for DNT."	( Combining in vitro assays and mathematical modelling to study developmental neurotoxicity induced by chemical mixtures. Bal-Price, A; Bopp, SK; Carpi, D; Mendoza-de Gyves, E; Paini, A; Pistollato, F; Worth, A, 2021)	0.62
"Intravenous valproate seems efficacious in reducing agitation in psychiatric patients; it generally appears safe compared to other neuroleptics or antiepileptics."	( Effectiveness and safety of intravenous valproate in agitation: a systematic review. Brondino, N; Cipriani, N; Civardi, S; Damiani, S; Donadeo, A; Olivola, M; Politi, P; Silva, A, 2022)	0.72
" We investigated potential transgenerational adverse effects of valproate."	( Transgenerational adverse effects of valproate? A patient report from 90 affected families. Bewley, S; Braillon, A; Hill, C; MacLennan, AH; Martin, M, 2022)	0.72
" Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis."	( An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels. Adebayo, RA; Anıl Yağcıoğlu, AE; Arrojo-Romero, M; Ayub, M; Baptista, T; Bebawi, E; Bhattacharya, R; Bilbily, J; Bonelli, RM; Bousman, CA; Buckley, PF; Celofiga, A; Chan, SKW; Chopra, N; Citrome, L; Cohen, D; Correll, CU; Cotes, RO; Crespo-Facorro, B; Cubała, WJ; De Berardis, D; De Las Cuevas, C; de Leon, J; Decloedt, E; Eap, CB; Elkis, H; Ertuğrul, A; Every-Palmer, S; Farooq, S; Fernandez-Egea, E; Fountoulakis, KN; Freudenreich, O; González-Esquivel, DF; Grover, S; Gründer, G; Hiemke, C; Iglesias-Alonso, A; Iglesias-Garcia, C; Ignjatovic Ristic, D; Jung-Cook, H; Kaithi, AR; Kane, JM; Kelly, DL; Kim, SH; Kim, YS; Kirilochev, OO; Kopeček, M; Lana, F; Lane, HY; Lazary, J; Leung, JG; Lin, SK; LLerena, A; López-Jaramillo, C; Marder, SR; Masmoudi, R; McCollum, B; McGrane, I; Mohd Saffian, S; Molden, E; Motuca, M; Müller, DJ; Ng, CH; Nielsen, J; Olmos, I; Ortiz, BB; Otsuka, Y; Ouanes, S; Pacheco Palha, AJ; Pedro, MR; Procyshyn, RM; Quiles, C; Rădulescu, FŞ; Rajkumar, AP; Ricciardi, C; Rohde, C; Ruan, CJ; Sagud, M; Sanz, EJ; Schoretsanitis, G; Schulte, PFJ; Seifritz, E; Seppälä, N; Shelton, C; Silva, A; Siskind, D; Smith, RL; Solismaa, A; Soloviev, A; Spina, E; Švancer, P; Takeuchi, H; Tang, YL; Temmingh, H; Torres, R; Tsukahara, M; Verdoux, H; Villagrán-Moreno, JM; Wang, CY; Wang, G; Weizman, A; Wilkowska, A; Yecora, A; Zolezzi, M, 2022)	0.72
" There were no serious adverse events."	( Efficacy and Safety of Repetitive Intravenous Sodium Valproate in Pediatric Patients With Refractory Chronic Headache Disorders: A Retrospective Review. Allen, I; Gelfand, AA; Pavitt, S; Riggins, N; Zorrilla, N, 2022)	0.72
" These findings were confirmed with histopathological changes where Ac was capable of reversing the toxic effects of valproic acid on liver cells CONCLUSION: It is concluded that Ac showed significant hepatoprotective effects at different doses in the animal model used in this study."	( Evaluation of the hepatoprotective activity of hydroalcoholic extract of Alhagi camelorum against valproic acid-induced hepatotoxicity in rats. Ahmed, MM; Andleeb, S; Arshad, S; Aslam, A; Iqbal, MO; Javaid, U; Khan, IA; Manzoor, M; Manzoor, Z; Mumtaz, A; Munawar, SH; Riaz, R, 2022)	1.15
" Different models were identified that provided accurate predictions for rat prenatal LELs and conservative estimates of human safe exposure."	( Quantitative in vitro to in vivo extrapolation for developmental toxicity potency of valproic acid analogues. Allen, D; Bell, S; Ceger, P; Chang, X; Cook, B; Donley, E; Kleinstreuer, N; Knudsen, TB; Lee, UJ; Lumen, A; Mansouri, K; Palmer, J; Sprankle, C; Wambaugh, J, 2022)	0.95
" The mainstay of treatment is with multiple anti-seizure medications (ASMs); however, the ASMs themselves can be associated with psychobehavioural adverse events, and effects (negative or positive) on cognition and sleep."	( Psychobehavioural and Cognitive Adverse Events of Anti-Seizure Medications for the Treatment of Developmental and Epileptic Encephalopathies. Schubert-Bast, S; Strzelczyk, A, 2022)	0.72
"This pilot study demonstrated that the dosage of 4 gr/daily of inositol is safe in patients taking Li/VPA, as we recorded no interference with the pharmacological therapy."	( Safety of inositol supplementation in patients taking lithium or valproic acid: a pilot clinical study. Cantelmi, T; Lepore, E; Unfer, V; Unfer, VR, 2022)	0.96
" There was no significant difference in the occurrence of common adverse drug reactions, such as drowsiness and fatigue, between the melatonin group and the comparison groups."	( Efficacy and Safety of Melatonin as Prophylaxis for Migraine in Adults: A Meta-analysis. Jena, M; Maiti, R; Mishra, A; Mishra, BR; Puliappadamb, HM, 2022)	0.72
" Meta-analysis showed no difference between lithium and placebo regarding severe adverse events (odds ratio = 1."	( Safety and efficacy of lithium in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis of randomized controlled trials. Al-Dardery, NM; Attia, AN; Hamad, AA; Meshref, M; Mohamed, SF, 2023)	0.91
" The present study explored the pharmacokinetics (PK) and exposure safety of DP-VPA to provide a basis for future studies exploring the safe dosage and therapeutic strategies for epilepsy."	( Population pharmacokinetics and exposure-safety of lipophilic conjugates prodrug DP-VPA in healthy Chinese subjects for dose regime exploring. Cao, G; Chen, Y; Fan, Y; Guo, B; Hu, J; Li, X; Li, Y; Liu, X; Wang, Y; Wu, H; Wu, J; Wu, X; Xu, X; Yu, J; Yu, P; Zhan, H; Zhang, J, 2023)	0.91
" We conclude that VPA is a safe and effective treatment option for MDS and AML patients, particularly when used in conjunction with all-trans retinoic acid, DNA-hypomethylating drugs, and hydralazine."	( Efficacy and Safety of Valproic Acid in Myelodysplastic Syndrome and Acute Myeloid Leukemia; a Narrative Review. Mahdiani, S; Mohammadpour, AH; Omidkhoda, N; Rahimi, H; Samadi, S, 2023)	1.22
" Therefore, knowledge about the typical adverse events (AEs) for ASMs and other coadministered drugs (CDs) is essential for practitioners and patients."	( Adverse Event Profiles of Antiseizure Medications and the Impact of Coadministration on Drug Tolerability in Adults with Epilepsy. Knake, S; Kovac, S; Rosenow, F; Strzelczyk, A; van der Goten, M; von Podewils, F; Willems, LM; Zöllner, JP, 2023)	0.91
" The adverse effects of VPA were extensively studied through the evaluations on the mortality, heartbeats, spontaneous tail coiling, and hatching rate."	( Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder. Azmai, MNA; Bakar, NA; Chong, SG; Fadzar, MSIM; Fahmi, MSAM; Faudzi, SMM; Hamid, NNAZZ; Ibrahim, WNW; Mastuki, SN; Norazhar, AI; Ramlan, NF; Saleh Hodin, NA; Zulkifli, AR, 2023)	1.18
" We should collaborate with obstetricians and other professionals to help ensure a safe environment for pregnancy and childbirth."	( [Safe and Effective Management of Epilepsy in Pregnancy]. Iwasaki, M; Kimura, Y, 2023)	0.91

Pharmacokinetics

Noninvasive, real-time pharmacokinetic (PK) monitoring of ketamine, propofol, and valproic acid, and their metabolites was achieved in mice.

Excerpt	Reference	Relevance
" Valproate was rapidly eliminated in both species, the half-life being 90--120 min in dogs (T0."	( Pharmacokinetics of sodium valproate in dog and mouse. Esenwein, H; Löscher, W, 1978)	0.26
"Anticonvulsant therapy was among the first areas to benefit from clinical pharmacokinetic studies."	( Clinical pharmacokinetics of anticonvulsants. Dam, M; Hvidberg, EF, 1976)	0.26
" The effects of other antiepileptics on the serum protein binding, erythrocyte distribution and metabolism of ZNS were also studied in vitro to elucidate the mechanism of pharmacokinetic interaction of ZNS."	( Pharmacokinetic interaction of zonisamide in rats. Effect of other antiepileptics on zonisamide. Fukuchi, H; Kimura, M; Kimura, Y; Kitaura, T; Miyake, K; Tanaka, N, 1992)	0.28
" It also had the lowest clearance and the longest half-life and mean residence time."	( Pharmacokinetic analysis of the structural requirements for forming "stable" analogues of valpromide. Bialer, M; Hadad, S; Haj-Yehia, A, 1992)	0.28
" It was concluded that with SR-VPA bid, the pharmacokinetic features were more stable, the age-related AUC value was larger and the clinical effect was better than in comparison to C-VPA tid in children with intractable epilepsy."	( A comparative clinical and pharmacokinetic study of a new slow-release versus conventional preparations of valproic acid in children with intractable epilepsy. Fukuyama, Y; Imaizumi, T; Izumi, T, 1992)	0.5
" In the foetus the plasma level of valproate and the protein binding are higher than in maternal plasma, and the half-life of valproate following placental transfer is considerably longer than in adults."	( Pharmacokinetics of valproate in pregnancy: mother-foetus-newborn. Johannessen, SI, 1992)	0.28
"Over the past 10 years, knowledge gained about the pharmacokinetic profiles of valproate and carbamazepine has increased the clinical effectiveness of their use."	( Pharmacokinetics of valproate and carbamazepine. Wilder, BJ, 1992)	0.28
" Pharmacokinetic experiments with trans-2-en-VPA indicated non-linear kinetics with dose-dependent elimination rate and enterohepatic recirculation."	( Pharmacokinetics, anticonvulsant efficacy, and adverse effects of trans-2-en-valproate after acute and chronic administration in amygdala-kindled rats. Hönack, D; Löscher, W; Rundfeldt, C, 1992)	0.28
"A prospective clinical pharmacokinetic study was carried out in 10 adult patients with primary or secondary generalized tonic-clonic seizures on the efficacy of valproic acid (VPA) administered as a single daily dose in comparison with divided doses thrice daily."	( [A single daily dose with valproic acid. A pharmacodynamic and clinical study]. Mamoli, B; Pelzl, G, 1992)	0.78
" Pharmacokinetic parameters were calculated using a two-compartment open model with a Michaelis-Menten-type elimination process from the central compartment."	( Pharmacokinetic analysis of the disposition of valproate in pregnant rats. Hanano, M; Iga, T; Kobayashi, S; Takai, K, )	0.13
" Pharmacokinetic studies indicate that both enantiomers of each compound reach the embryo to the same degree."	( Valproic acid-induced neural tube defects in mouse and human: aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms. Ehlers, K; Hauck, RS; Nau, H, 1991)	1.72
" The pharmacokinetic parameters, necessary to define the pharmacokinetics of valproic acid, were calculated both after single dose: Cmax, tmax, kel, t1/2, Vd, AUC and Cl, and at steady state: Cminss Cmaxss and Fl%."	( Single dose and steady state pharmacokinetics of valproic acid in adult epileptic patients. Lević, Z; Miljković, B; Pokrajac, M; Varagić, V, 1991)	0.76
" As the values of CL and V increased similarly during the dark period, there was no effect on half-life (t 1/2) and obviously on the elimination rate constant (K)."	( Chronopharmacokinetics of valproic acid following constant-rate administration in mice. Nakano, S; Ogawa, N; Ohdo, S, 1991)	0.58
" For the 2 extravascular routes, the absolute bioavailability F, maximal plasma concentrations Cmax, times to peak Tmax and absorption coefficients Kabs were the same."	( Effects of administration route on valproate pharmacokinetics in the rabbit. Bourin, M; Guenzet, J; Kergueris, MF; Larousse, C; Ortega, A; Thomare, P, 1991)	0.28
"01) in the AUC and the elimination half-life (t1/2) were observed in the salicylate-treated rats."	( Drug interaction. Effects of salicylate on pharmacokinetics of valproic acid in rats. Hanano, M; Shen, YZ; Sugiyama, Y; Yu, HY, )	0.37
" We also present data not previously reported, which describes the pharmacokinetic disposition of valproic acid and several of its metabolites during the course of this acute overdose."	( Acute valproic acid overdose. Clinical course and pharmacokinetic disposition of valproic acid and metabolites. Dupuis, RE; Lichtman, SN; Pollack, GM, )	0.83
"The pharmacokinetic and pharmacodynamic properties of the spiro carboxylic acid, spiro[4."	( Pharmacokinetics and pharmacodynamics of valproate analogues in rats. I. Spiro[4.6]undecane-2-carboxylic acid. Liu, MJ; Pollack, GM; Scott, KR, )	0.13
" MPD, the least-branched compound had the largest clearance and shortest half-life of all the amides investigated and was the least active."	( Structure-pharmacokinetic relationships in a series of valpromide derivatives with antiepileptic activity. Bialer, M; Haj-Yehia, A, 1989)	0.28
"Drugs labeled with stable isotopes have been successfully used in pharmacokinetic drug interaction studies."	( Pharmacokinetic drug interactions. Eichelbaum, M, )	0.13
"The influence of progabide, a new antiepileptic drug, on the pharmacokinetic profiles of phenobarbital, phenytoin, carbamazepine, and valproic acid was evaluated in four separate studies, each including six young healthy volunteers."	( Pharmacokinetic interactions of progabide with other antiepileptic drugs. Bianchetti, G; Morselli, PL; Padovani, P; Thénot, JP; Thiercelin, JF, )	0.33
"Interspecies differences in regard to the teratogenicity of drugs can be the result of differing pharmacokinetic processes that determine the crucial concentration-time relationships in the embryo."	( Species differences in pharmacokinetics and drug teratogenesis. Nau, H, 1986)	0.27
"02) of AUC which was considered the most important pharmacokinetic parameter in the CPM therapy."	( Effect of valproic acid on pharmacokinetics of active metabolites of cyclophosphamide in mice. Goto, M; Johno, I; Kitazawa, S; Ohnishi, C; Yamashina, H, 1987)	0.68
" Pharmacokinetic parameters were calculated based upon a two-compartment model."	( Dose-dependent pharmacokinetics of valproate in guinea pigs of different ages. Hanano, M; Shen, YZ; Sugiyama, Y; Yu, HY, )	0.13
"To predict the plasma concentrations after percutaneous application of valproic acid (VPA), we presented a new pharmacokinetic model which includes simultaneous two absorption processes through the skin."	( A pharmacokinetic model for percutaneous absorption of valproic acid and prediction of drug disposition. Atago, H; Ito, Y; Iwaki, M; Ogiso, T; Yamamoto, Y, 1988)	0.76
" The terminal half-life of free VPA (6."	( Pharmacokinetics of free and total sodium valproate in adolescents and young adults during maintenance therapy. Herngren, L; Nergårdh, A, 1988)	0.27
" There was no significant change in pharmacokinetic parameters (maternal plasma elimination rate, area under the curve, peak plasma concentration) between the first and last days of treatment at either dose level."	( Valproic acid developmental toxicity and pharmacokinetics in the rhesus monkey: an interspecies comparison. Binkerd, P; Cukierski, MA; Cukierski, MJ; Hendrickx, AG; Nau, H; Rowland, JM; Rowland, JR, 1988)	1.72
" For most of these formulations bio-availability approaches 100%, while the absorption half-life varies from less than 30 minutes to 3 or 4 hours depending on the type of preparation used."	( Clinical pharmacokinetics of valproic acid--1988. Messori, A; Moroni, F; Zaccara, G, 1988)	0.57
" Of the pharmacokinetic parameters studied, total and intrinsic clearance, distribution volume, and valproic acid free fraction were significantly increased in the very high dose group."	( Valproic acid pharmacokinetics in children: III. Very high dosage requirements. Cloyd, JC; Fischer, JH; Fraser, GL; Green, KH; Kriel, RL, )	1.79
"01), and shorter half-life (9."	( Comparison of steady-state pharmacokinetics of valproic acid in children between monotherapy and multiple antiepileptic drug treatment. Chiba, K; Hori, M; Iriki, T; Ishizaki, T; Naitoh, H; Shirai, Y; Suganuma, T, 1985)	0.53
" VPA half-life calculated from the urine data of the metabolite was shorter than the half-life calculated from the blood data."	( Pharmacokinetics of valproic acid in volunteers after a single dose study. Abramsky, O; Bialer, M; Herishanu, Y; Hussein, Z; Pachys, F; Raz, I, )	0.45
" Pharmacokinetic parameters were studied and statistically analyzed after an intravenous single dose of 20 mg/kg of sodium valproate."	( Changes in pharmacokinetics of valproic acid in guinea pigs from birth to maturity. Hanano, M; Sugiyama, Y; Yu, HY, )	0.42
" The half-life of VPA was significantly related to age, but volume of distribution and clearance were not."	( A multivariable analysis of factors governing the steady-state pharmacokinetics of valproic acid in 52 young epileptics. Hall, K; Irvine-Meek, J; Johnston, B; Leroux, M; Otten, N; Seshia, S, )	0.36
"Various pharmacokinetic parameters--disposition half-life, t1/2,z, metabolic clearance CLm, volume of distribution V, intrinsic clearance of unbound drug CLuint, and unbound volume of distribution of tissues (distributive tissue volume/fraction of drug in tissue unbound, VT/fuT--are compared in rat and human for nine weakly acidic drugs, phenytoin, hexobarbital, pentobarbital, phenylbutazone, warfarin, tolbutamide, valproate, phenobarbital, and amobarbital, and six weakly basic drugs, quinidine, chlorpromazine, propranolol, pentazocin, antipyrine, and diazepam."	( Prediction of the disposition of nine weakly acidic and six weakly basic drugs in humans from pharmacokinetic parameters in rats. Hanano, M; Iga, T; Sawada, Y; Sugiyama, Y, 1985)	0.27
" Pharmacokinetic interactions between antiepileptic drugs may lead to considerable fluctuation in plasma drug concentration, and monotherapy is often preferable."	( Pharmacokinetics of antiepileptic drugs. Neuvonen, PJ; Tokola, RA, 1983)	0.27
" Four to 5 Cmin were monitored just before the morning valproic acid dose for 3 to 4 days preceding the kinetic study."	( The effects of neuroleptics (haloperidol and chlorpromazine) on the pharmacokinetics of valproic acid in schizophrenic patients. Chiba, K; Iizuka, R; Ishizaki, T; Kobayashi, K; Saito, M, 1984)	0.74
" Significant differences occurred between initial and maintenance therapy in the mean apparent volume of distribution and in apparent VPA clearance, whereas VPA half-life remained relatively constant."	( Pharmacokinetics of valproic acid in children: I. Multiple antiepileptic drug therapy. Cloyd, JC; Eggerth, RM; Fischer, JH; Kriel, RL; Sawchuk, RJ, 1983)	0.59
" Depending on its pharmacokinetic parameters, each drug effect has a different onset, intensity, and time course."	( Clinical pharmacokinetics of drugs used in the treatment of status epilepticus. Baars, AM; van der Dries, A; van der Kleijn, E; Vree, TB, 1983)	0.27
"A pharmacokinetic study of sodium valproate (DPA) was undertaken in children treated with this drug after a febrile convulsion."	( [Pharmacokinetic elements of sodium valproate. Use in febrile convulsions in children]. Beaune, P; Lenoir, G; Novella-Pequinot, MA; Perignon, F, 1983)	0.27
" Serum level decline was biphasic in both instances with a terminal half-life of 27."	( The effects of peritoneal dialysis on the single dose and steady state pharmacokinetics of valproic acid in a uremic epileptic child. Abbott, FS; Farrell, K; Ferguson, S; Godolphin, WJ; Orr, JM, 1983)	0.49
" Total body clearance (CL), half-life (t 1/2), and apparent volume of distribution (Vd) were calculated from the terminal portion of the curve and from the area under the serum concentration-time curve (AUC)."	( First-dose and steady-state pharmacokinetics of valproic acid in children with seizures. Budnick, D; Hall, K; Irvine-Meek, J; Leroux, M; Otten, N; Seshia, SS; Verma, M, )	0.39
"0 micrograms/ml at 1 h and declined monoexponentially, with a terminal half-life of 14."	( Pharmacokinetics of valproic acid obtained after administration of three oral formulations to humans. Abramsky, O; Bialer, M; Dubrovsky, J; Hussein, Z; Raz, I, 1984)	0.59
"The present pharmacokinetic study was designed to investigate the possible interaction between valproic acid (VPA) and ethosuximide (ESM) in humans."	( Valproic acid-ethosuximide interaction: a pharmacokinetic study. Di Perri, R; Fazio, A; La Rosa, G; Narbone, MC; Oteri, G; Pisani, F; Trunfio, C, 1984)	1.93
" Pharmacokinetic parameters were equivalent for both preparations except for an absorption lag with the enteric-coated form."	( Pharmacokinetics of enteric-coated valproic acid. Albright, PS; Bruni, J; Suria, D, 1984)	0.54
"Di-[( 3,3,3-2H3]propyl)acetic acid, a hexadeuterated analogue of valproic acid, was synthesized and its pharmacokinetic properties compared with valproic acid."	( Use of hexadeuterated valproic acid and gas chromatography-mass spectrometry to determine the pharmacokinetics of valproic acid. Abbott, FS; Acheampong, AA; Burton, RW; Ferguson, SM; Orr, JM, 1984)	0.82
" These findings suggest that the pharmacokinetic alterations of VPA in old age are complex and include at least two separate mechanisms: a decrease in plasma protein binding and a reduction of drug metabolizing capacity resulting in decreased clearance of free drug by the liver."	( Pharmacokinetics of valproic acid in the elderly. Crema, F; Frigo, GM; Gatti, G; Grimaldi, R; Perucca, E; Pirracchio, S, 1984)	0.59
"Free and total valproic acid (VPA) pharmacokinetic evaluation was carried out at steady state in six young epileptics who were also receiving other anticonvulsants."	( Free valproic acid: steady-state pharmacokinetics in patients with intractable epilepsy. Budnik, D; Hall, K; Irvine-Meek, J; Leroux, M; Otten, N; Seshia, S, 1984)	1.13
" The multi compartment polyexponential pharmacokinetic models have classically been fit to data using nonlinear regression programs such as NonLin (Metzler, 1969)."	( New method that gives true least squares fit of one and two compartment open pharmacokinetic models applied to valproic acid and methadone. Gerber, N; Lawyer, CH, 1980)	0.47
" VPA was excreted in the neonates with a mean half-life of 47 +/- 15 hr (n = 8) which is approximately 4 times the mean value found in adult epileptics."	( Valproic acid and its metabolites: placental transfer, neonatal pharmacokinetics, transfer via mother's milk and clinical status in neonates of epileptic mothers. Häuser, I; Helge, H; Koch, S; Nau, H; Rating, D, 1981)	1.71
" After a single intravenous dose of 1,000 mg valproic acid, the pharmacokinetic parameters were determined according to the open two-compartment model."	( The pharmacokinetics of valproic acid after oral and parenteral administration in healthy volunteers. Mascher, H; Nitsche, V, 1982)	0.83
" A multicompartment first-order materno-fetal pharmacokinetic model is presented."	( Materno-fetal pharmacokinetics and fetal distribution of valproic acid in a pregnant rhesus monkey. Cook, MJ; Dickinson, RG; Gerber, N; Kaufman, SN; Lawyer, CH; Lynn, RK; Novy, MJ, 1980)	0.51
"Results of clinical and pharmacokinetic observations on sodium valproate (VPA) are reported from a long-term study in 100 children with epilepsy."	( Clinical and pharmacokinetic observations on sodium valproate - a 5-year follow-up study in 100 children with epilepsy. Henriksen, O; Johannessen, SI, 1982)	0.26
" Removal of the implanted pumps and measurement of the decay of the drug levels revealed that the half-life of the main plasma metabolite 2-en(2-propyl-2-pentenoic acid) exceeded that of VPA."	( Pharmacokinetics of valproic acid and metabolites in mouse plasma and brain following constant-rate application of the drug and its unsaturated metabolite with an osmotic delivery system. Nau, H; Zierer, R, )	0.45
" This review contains relevant pharmacokinetic data on anticonvulsant drugs widely used during pregnancy and the neonatal period."	( Anticonvulsants during pregnancy and lactation. Transplacental, maternal and neonatal pharmacokinetics. Egger, HJ; Helge, H; Kuhnz, W; Nau, H; Rating, D, )	0.13
" A one-compartment model was assumed for calculation of the relevant pharmacokinetic parameters."	( Pharmacokinetic study of valproic acid in a neonate. Budnik, D; Hall, KW; Irvine-Meek, JM; Leroux, M; Otten, NH; Seshia, SS, 1982)	0.57
"Therapeutic drug monitoring (TDM) of chronic treatments is justified for several reasons, including relative over- or underdosage due to variable individual elimination, pharmacokinetic interactions in drug combinations, and noncompliance."	( Validation of a quick modeling program generating clearance estimates at steady state for routine therapeutic drug monitoring. Alric, R; Beglia, S; el Battah, A, 1995)	0.29
" Neither the serum concentrations nor the pharmacokinetic parameters of sodium valproate (SV) were altered by the coadministration of aminophylline (AMP)."	( Aminophylline alters pharmacokinetics of carbamazepine but not that of sodium valproate--a single dose pharmacokinetic study in human volunteers. David, J; Joseph, T; Kulkarni, C; Vaz, J, 1995)	0.29
"Only valproyl glycinamide showed a good anticonvulsant profile in both mice and rats due to its better pharmacokinetic profile."	( Pharmacokinetic analysis and antiepileptic activity of N-valproyl derivatives of GABA and glycine. Bialer, M; Hadad, S, 1995)	0.29
" The current study demonstrates the benefit of the SPPR approach in developing and selecting a potent antiepileptic compound in intact animals based not only on its intrinsic pharmacodynamic activity, but also on its better pharmacokinetic profile."	( Pharmacokinetic analysis and antiepileptic activity of N-valproyl derivatives of GABA and glycine. Bialer, M; Hadad, S, 1995)	0.29
" On the other hand, the peak concentration and duration of exposure to valproic acid and ethylhexanoic acid were very similar despite a more severe teratologic outcome following valproic acid, which indicated higher intrinsic activity of this latter agent."	( Pharmacokinetic determinants of embryotoxicity in rats associated with organic acids. Collins, MD; Nau, H; Scott, WJ, 1994)	0.52
"To evaluate an animal model of multiple-dose activated charcoal (MDAC) therapy and correlate the pharmacokinetic properties of four drugs with the efficacy of MDAC."	( Correlation of drug pharmacokinetics and effectiveness of multiple-dose activated charcoal therapy. Chyka, PA; Holley, JE; Mandrell, TD; Sugathan, P, 1995)	0.29
" A review of published studies involving small numbers of elderly subjects or patients given phenytoin sodium, valproic acid, or carbamazepine demonstrates decreased protein binding and intrinsic clearance and increased half-life with advancing age."	( Antiepileptics in the elderly. Pharmacoepidemiology and pharmacokinetics. Cloyd, JC; Lackner, TE; Leppik, IE, 1994)	0.5
" An understanding of the underlying pharmacokinetic processes, including the need of most elderly patients for lower doses and longer dosing intervals, permits more effective management of therapy and reduces the risk for adverse reactions."	( Antiepileptics in the elderly. Pharmacoepidemiology and pharmacokinetics. Cloyd, JC; Lackner, TE; Leppik, IE, 1994)	0.29
"Zidovudine is metabolized to an inactive 5'-glucuronide and has a short plasma half-life requiring frequent dosing."	( Pharmacokinetic interaction between zidovudine and valproic acid in patients infected with human immunodeficiency virus. Agrawal, KC; Akula, S; George, WJ; Greenspan, DL; Hyslop, NE; Lertora, JJ; Rege, AB, 1994)	0.54
" Between-regimen steady-state comparisons of pharmacokinetic parameters revealed some significant differences in mean time to Cmax (Tmax), Cmax, Cmin, AUC, and total body clearance for respective day-4 dosing intervals, but not for the entire day 4, except for Cmin and Tmax."	( Pharmacokinetics of valproate after multiple-dose oral and intravenous infusion administration: gastrointestinal-related diurnal variation. Cavanaugh, JH; Granneman, GR; Hussein, Z; Lamm, J; Mukherjee, D, 1994)	0.29
" In this context, anticonvulsant and neurotoxic pharmacodynamic interactions between phenytoin (PHT) and valproate (VPA) were assessed in an experimental model in mice."	( Pharmacodynamic interactions between phenytoin and valproate: individual and combined antiepileptic and neurotoxic actions in mice. Bourgeois, BF; Chez, MG; Knowles, WD; Pippenger, CE, 1994)	0.29
" An optimal antiepileptic clinical effect of VPA was achieved thanks to therapeutic monitoring, especially pharmacokinetic studies."	( Clinical and pharmacokinetic observations on valproate: a 3 year follow-up study in 100 children with generalized epilepsy. Galas-Zgorzalewicz, B; Steinborn, B, )	0.13
" The Cmax and Tmax values of the test formulation were significantly different from the values of the reference in single-(Tmax: 158."	( Pharmacokinetic comparison of two valproic acid formulations--a plain and a controlled release enteric-coated tablets. Chong, WS; Jang, IJ; Lee, KH; Lee, N; Myung, HJ; Rha, JH; Shin, SG, 1993)	0.57
" The pharmacokinetic parameters were determined by both non-compartmental and model-dependent techniques."	( Effect of infusion duration on valproate pharmacokinetics. Cavanaugh, JH; Granneman, GR; Hussein, Z; Lamm, JE; Patterson, KJ, 1993)	0.29
"h ml-1), in the mean residence time (28 h), or in the elimination half-life (16 h)."	( Influence of food intake on the pharmacokinetics of a sustained release formulation of sodium valproate. Jacob, F; Lascombes, F; Necciari, J; Royer, RJ; Royer-Morrot, MJ; Zhiri, A, 1993)	0.29
" These results suggest that ZNS has little effect on the pharmacokinetic behaviors of other antiepileptic drugs."	( Pharmacokinetic interaction of zonisamide in rats. Effect of zonisamide on other antiepileptics. Fukuchi, H; Kimura, M; Kimura, Y; Kitaura, T; Miyake, K; Tanaka, N, 1993)	0.29
"05) variability in pharmacokinetic values than patients receiving monotherapy."	( Valproic acid pharmacokinetics in children. IV. Effects of age and antiepileptic drugs on protein binding and intrinsic clearance. Cloyd, JC; Fischer, JH; Kraus, DM; Kriel, RL, 1993)	1.73
" The anticonvulsant activity is explained on pharmacokinetic and pharmacodynamic grounds due to its complete conversion to VPA and the possible synergism in anticonvulsant activity between VPA and 1,4-butanediol."	( Pharmacokinetic analysis and anticonvulsant activity of two polyesteric prodrugs of valproic acid. Bialer, M; Hadad, S; van der Kleijn, E; Vree, TB, 1993)	0.51
" Particular attention has been paid to the role of age in determining the variability of pharmacokinetic parameters, but the effect of other factors, such as different formulations and routes of administration, concomitant treatments, gender and pathological conditions other than epilepsy, have also been considered."	( Clinical pharmacokinetics of antiepileptic drugs in paediatric patients. Part I: Phenobarbital, primidone, valproic acid, ethosuximide and mesuximide. Avanzini, G; Battino, D; Estienne, M, 1995)	0.5
"We evaluated the pharmacokinetic effects and safety of coadministration of lithium and valproate in 16 healthy volunteers in this randomized, placebo-controlled, two-period (12 days each) crossover trial."	( Pharmacokinetic interactions and side effects resulting from concomitant administration of lithium and divalproex sodium. Cavanaugh, JH; Granneman, GR; Schneck, DW; Witt, GF, 1996)	0.29
" A pharmacokinetic model was developed to describe the influence of phenobarbital on the hepatobiliary disposition of VPA and valproate glucuronide (V-G) in the IPL; all processes governing VPA and V-G disposition appeared to be linear."	( Hepatobiliary disposition of valproic acid and valproate glucuronide: use of a pharmacokinetic model to examine the rate-limiting steps and potential sites of drug interactions. Booth, CL; Brouwer, KL; Pollack, GM, 1996)	0.59
" Valproic acid elimination half-life was 3 h during the 190 min hemoperfusion cycle."	( Delayed peak serum valproic acid in massive divalproex overdose--treatment with charcoal hemoperfusion. Aaron, CK; Graudins, A, 1996)	1.53
" The median elimination half-life (t1/2) in patients receiving concomitant valproate (VPA) was 43."	( Pharmacokinetic interactions between lamotrigine and other antiepileptic drugs in children with intractable epilepsy. Boreus, L; Eriksson, AS; Hoppu, K; Nergårdh, A, 1996)	0.29
" Estimation of the pharmacokinetic parameters in each drug was performed by Higuchi's Bayesian program, PEDA Pearson's correlation coefficient (r) between clearance and body weight was calculated for each drug."	( Clearance of phenytoin and valproic acid is affected by a small body weight reduction in an epileptic obese patient: a case study. Ashikari, Y; Chiba, S; Kodama, Y; Kuranari, M; Sakata, T; Takeyama, M, 1996)	0.59
" Routine clinical pharmacokinetic data (N = 1,010) collected from 466 patients receiving carbamazepine were analyzed according to a simple steady-state pharmacokinetic model with the use of NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data."	( Detection of carbamazepine drug interaction by multiple peak approach screening using routine clinical pharmacokinetic data. Aoyama, T; Yukawa, E, 1996)	0.29
" Out of the investigated compounds only (E)-2-ene valproyl glycinamide showed a good anticonvulsant profile in both mice and rats due to its better pharmacokinetic and pharmacodynamic profile."	( Pharmacokinetic and pharmacodynamic analysis of (E)-2-ene valproyl derivatives of glycine and valproyl derivatives of nipecotic acid. Abdul-Hai, A; Bialer, M; Haj-Yehia, A; Herzig, Y; Kadry, B; Shirvan, M; Sterling, J, 1996)	0.29
" Clearance, volume of distribution, and elimination half-life were scaled up from animal data obtained from literature."	( Interspecies scaling: predicting pharmacokinetic parameters of antiepileptic drugs in humans from animals with special emphasis on clearance. Balian, JD; Mahmood, I, 1996)	0.29
"The described structure pharmacokinetic pharmacodynamic relationships (SPPR) study explored the utilization of tetramethylcyclopropane analogues of valpromide (VPD), or tetramethylcyclopropane carboxamide derivatives of valproic acid (VPA) as new antiepileptics."	( Pharmacokinetic analysis and antiepileptic activity of tetra-methylcyclopropane analogues of valpromide. Abdul-Hai, A; Bialer, M; Hadad, S; Haj-Yehia, A; Herzig, Y; Kadry, B; Sterling, J; Yagen, B, 1996)	0.48
" Routine clinical pharmacokinetic data (n = 474) was collected from 250 patients receiving valproic acid and no other drug."	( A feasibility study of the multiple-peak approach for pharmacokinetic screening: population-based investigation of valproic acid relative clearance using routine clinical pharmacokinetic data. Yukawa, E, 1995)	0.72
" This investigation was carried out to compare 4-ene VPA and the alpha-fluorinated analogue (alpha-fluoro-4-ene VPA) for their pharmacokinetic and protein binding properties."	( A comparative investigation of 2-propyl-4-pentenoic acid (4-ene VPA) and its alpha-fluorinated analogue: phase II metabolism and pharmacokinetics. Abbott, FS; Tang, W, 1997)	0.3
" None of the norethindrone pharmacokinetic parameters changed significantly in the presence of topiramate."	( Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy. Doose, DR; Nayak, RK; Rosenfeld, WE; Walker, SA, 1997)	0.3
"The steady-state pharmacokinetics of valproate (VPA) and topiramate (TPM) were compared during VPA monotherapy, concomitant VPA and TPM therapy, and TPM monotherapy to evaluate pharmacokinetic interactions."	( Comparison of the steady-state pharmacokinetics of topiramate and valproate in patients with epilepsy during monotherapy and concomitant therapy. Anderson, G; Kramer, LD; Levy, RH; Liao, S; Nayak, RK; Palmer, M; Rosenfeld, WE, 1997)	0.3
" TPM plasma peak concentration (C(max)) and area under the concentration-versus-time curve during a 12-h dosing interval (AUC(0-12)) were slightly higher (17%; n = 8) during TPM monotherapy than during concomitant VPA therapy."	( Comparison of the steady-state pharmacokinetics of topiramate and valproate in patients with epilepsy during monotherapy and concomitant therapy. Anderson, G; Kramer, LD; Levy, RH; Liao, S; Nayak, RK; Palmer, M; Rosenfeld, WE, 1997)	0.3
" VPA-HA and HEV showed improved anticonvulsant activity over VPA because of their greater intrinsic activity and not due to better pharmacokinetic characteristics."	( Pharmacokinetics and antiepileptic activity of valproyl hydroxamic acid derivatives. Bialer, M; Levi, M; Yagen, B, 1997)	0.3
" We conclude that the pharmacokinetic requirements for therapeutic drug monitoring of VPA are established."	( Pharmacokinetics of valproic acid in patients with juvenile myoclonic epilepsy on monotherapy. Lundkvist, B; Sundqvist, A; Tomson, T, 1997)	0.62
" Dose-normalized Cmax was higher in children taking valproate (18."	( A single-dose study to define tiagabine pharmacokinetics in pediatric patients with complex partial seizures. Boellner, SW; el-Shourbagy, T; Granneman, GR; Guenther, HJ; Gustavson, LE; Qian, JX; Sommerville, KW, 1997)	0.3
" Pharmacokinetic properties of valproate did not change significantly in the ten available participants during coadministration of lorazepam."	( Effect of valproate on the pharmacokinetics and pharmacodynamics of lorazepam. Cavanaugh, JH; Granneman, RG; Samara, EE; Witt, GF, 1997)	0.3
" The mean area under the concentration-time curve, peak concentration and pre-dose concentration of VPA were unchanged by remacemide hydrochloride in three patients on the higher and in 10 patients on the lower dose of remacemide."	( Lack of pharmacokinetic interaction between remacemide hydrochloride and sodium valproate in epileptic patients. Brodie, MJ; Girvan, J; Jamieson, V; Jones, T; Leach, JP; Richens, A, 1997)	0.3
" No clinically relevant pharmacokinetic interactions were noted between felbamate and lamotrigine, clonazepam, vigabatrin, nor the active monohydroxy metabolite of oxcarbazepine."	( Pharmacokinetic interactions with felbamate. In vitro-in vivo correlation. Banfield, CR; Glue, P; Levy, RH; Mather, GG; Perhach, JL; Racha, JK, 1997)	0.3
" Routine clinical pharmacokinetic data (n = 479) were collected from 207 epilepsy patients on combination therapy."	( Detection of carbamazepine-induced changes in valproic acid relative clearance in man by simple pharmacokinetic screening. Aoyama, T; Higuchi, S; Honda, T; Ohdo, S; Yukawa, E, 1997)	0.56
" The rate of elimination was not affected (terminal half-life approximately 15 h)."	( Influence of food on the pharmacokinetics of a new multiple unit sustained release sodium valproate formulation. Retzow, A; Vens-Cappell, B; Wangemann, M, 1997)	0.3
"The present study evaluates effect of pharmacokinetic interaction between caffeine (300 mg) in three divided doses with sodium valproate (400 mg) and carbamazepine (200 mg) given as single doses, in normal human volunteers, using a open cross over design."	( Influence of caffeine on pharmacokinetic profile of sodium valproate and carbamazepine in normal human volunteers. David, J; Joseph, T; Kulkarni, C; Vaz, J, 1998)	0.3
" Factors such as inter- and intraindividual pharmacokinetic variability and changes in AZT intracellular concentrations should be considered as other mechanisms responsible for changes in AZT pharmacokinetics with concomitant therapies."	( Glucuronidation of 3'-azido-3'-deoxythymidine (zidovudine) by human liver microsomes: relevance to clinical pharmacokinetic interactions with atovaquone, fluconazole, methadone, and valproic acid. Collins, JM; Jamis-Dow, C; Klecker, RW; Trapnell, CB, 1998)	0.49
"The relationship between clearance and age should be useful when establishing a pharmacokinetic programme for VPA monotherapy in children."	( Valproic acid clearance in children with epilepsy. López, E; Quintana, MB; Rodríguez, I; Sánchez-Alcaraz, A, 1998)	1.74
" It is concluded that the synergism may be due to a pharmacodynamic rather than a pharmacokinetic interaction."	( Pharmacodynamic interaction between phenytoin and sodium valproate changes seizure thresholds and pattern. Danhof, M; Della Paschoa, OE; Hamstra, R; Kruk, MR; Voskuyl, RA, 1998)	0.3
" PHT pharmacokinetics was described by a pharmacokinetic model with Michaelis-Menten elimination."	( Modelling of the pharmacodynamic interaction between phenytoin and sodium valproate. Danhof, M; Della Paschoa, OE; Voskuyl, RA, 1998)	0.3
" No significant changes were observed in the mean values of OXC pharmacokinetic parameters (Cmax, Tmax, t1/2 and AUC0-infinity) between the control and the pre-treated groups."	( Effect of valproic acid on the pharmacokinetic profile of oxcarbazepine in the rat. al-Hassan, MI; Bawazir, SA; Matar, KM; Nicholls, PJ; Tekle, A, 1999)	0.71
" The small decreases in mean valproic acid Cmax and AUC0-tau observed during the concomitant administration of tiagabine and valproate are probably of limited clinical importance, given the broad therapeutic range of valproate (50-100 microg/mL)."	( Lack of a clinically significant pharmacokinetic drug interaction between tiagabine and valproate. Boellner, SW; Granneman, GR; Guenther, HJ; Gustavson, LE; Sommerville, KW; Witt, GF, 1998)	0.59
"A population pharmacokinetic model is proposed to estimate the individual CL for paediatric patients receiving VPA in terms of patient's dose, weight and concomitant CBZ, in order to establish a priori dosage regimens."	( Valproate population pharmacokinetics in children. Buelga, DS; Domínguez-Gil, A; García Sánchez, MJ; Otero, MJ; Serrano, BB; Serrano, J, 1999)	0.3
" The objective of this study was to derive population pharmacokinetic (PK) parameters for valproate in healthy volunteers and to test the ability of these PK parameters to estimate concentrations in adult psychiatric patients using a Bayesian program."	( Prediction of valproate serum concentrations in adult psychiatric patients using Bayesian model estimations with NPEM2 population pharmacokinetic parameters. Lum, BL; Puentes, E; Puzantian, T, 1999)	0.3
" Despite methodologic limitations in the nonrandomized treatment sequence, these findings suggest that VPA and LTG exhibit a favorable pharmacodynamic interaction in patients with refractory partial epilepsy."	( The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction. Di Perri, R; Oteri, G; Perucca, E; Pisani, F; Richens, A; Russo, MF, 1999)	0.3
" We utilized pharmacokinetic considerations in designing various amide derivatives of VPA which are more potent as anticonvulsants than VPA and have the potential to be nonteratogenic and nonhepatotoxic."	( Pharmacokinetic considerations in the design of better and safer new antiepileptic drugs. Bialer, M, 1999)	0.3
"Following intravenous administration to dogs of the individual enantiomers, (R)-PID had significantly lower clearance and longer half-life than (S)-PID, however, the volumes of distribution were similar."	( Stereoselective pharmacokinetics and pharmacodynamics of propylisopropyl acetamide, a CNS-active chiral amide analog of valproic acid. Bennett, GD; Bialer, M; Finnell, RH; Levy, RH; Roeder, M; Schurig, V; Spiegelstein, O; Yagen, B, 1999)	0.51
"(R)-PID demonstrated better anticonvulsant activity, lower clearance and a longer half-life compared to (S)-PID."	( Stereoselective pharmacokinetics and pharmacodynamics of propylisopropyl acetamide, a CNS-active chiral amide analog of valproic acid. Bennett, GD; Bialer, M; Finnell, RH; Levy, RH; Roeder, M; Schurig, V; Spiegelstein, O; Yagen, B, 1999)	0.51
" The half-life of plasma disappearance of valproate was 25% reduced by lithium pretreatment (0."	( Effects of lithium on the pharmacokinetics of valproate in rats. Ida, S; Nishimoto, A; Shibata, S; Sugawara, A; Takiguchi, Y; Yokota, M; Yoshioka, H, 2000)	0.31
" During Ramadan, a significant decrease was observed in the Cmax (56."	( Influence of Ramadan on the pharmacokinetics of a single oral dose of valproic acid administered at two different times. Aadil, N; Benaji, B; Diquet, B; Fassi-Fihri, A; Hakkou, F; Houti, I; Kotbi, S; Ouhakki, M, 2000)	0.54
" The elimination half-life of the drug was much longer in the newborn (18."	( Disposition of valproic acid in maternal, fetal, and newborn sheep. I: placental transfer, plasma protein binding, and clearance. Abbott, FS; Kumar, S; Riggs, KW; Rurak, DW; Wong, H; Yeung, SA, 2000)	0.66
" Pharmacokinetic interactions between antiepileptic drugs represent a major complication of epilepsy treatment with polytherapy."	( Investigation of phenobarbital-carbamazepine-valproic acid interactions using population pharmacokinetic analysis for optimisation of antiepileptic drug therapy: an overview. Yukawa, E, 2000)	0.57
" This pharmacokinetic behavior offers easier treatment management as dose adjustment is facilitated."	( Study on the dose proportionality of the pharmacokinetics of sustained release sodium valproate. Mazur, D; Retzow, A; Vens-Cappell, B; Wangemann, M, 2000)	0.31
"to describe the population pharmacokinetics of lamotrigine (LTG) in developmentally disabled (DD) patients with epilepsy and (2) to determine if there is an effect of valproate (VPA) concentration on the extent of the pharmacokinetic interaction between VPA and LTG."	( Lack of an effect of valproate concentration on lamotrigine pharmacokinetics in developmentally disabled patients with epilepsy. Anderson, GD; Gidal, BE; Lanning, A; Rutecki, PR; Shaw, R, 2000)	0.31
" Statistical comparisons of pharmacokinetic parameters were performed with the Student paired t-test."	( Lack of pharmacokinetic interaction between valproic acid and a traditional Chinese medicine, Paeoniae Radix, in healthy volunteers. Chen, LC; Chou, MH; Lin, MF; Yang, LL, 2000)	0.57
" The plasma level of VPA declined with a half-life of 11."	( Lack of pharmacokinetic interaction between valproic acid and a traditional Chinese medicine, Paeoniae Radix, in healthy volunteers. Chen, LC; Chou, MH; Lin, MF; Yang, LL, 2000)	0.57
" To avoid complex pharmacokinetic interactions among multiple antiepileptic drugs, the data on serum concentrations in the current study were collected from patients who were co-administered only one additional antiepileptic drug (phenobarbital-carbamazepine, phenobarbital-valproic acid, or carbamazepine-valproic acid) or who received monotherapy."	( Pharmacokinetic interactions among phenobarbital, carbamazepine, and valproic acid in pediatric Japanese patients: clinical considerations on steady-state serum concentration-dose ratios. Aoyama, T; Higuchi, S; Hokazono, T; Ohdo, S; Satou, M; Yukawa, E, 2000)	0.72
"To quantitatively describe the pharmacokinetics of valproic acid (VPA) in guinea pig serum (total [Cf+b] and free [Cf]), cerebrospinal fluid (CSF) [C]CSF and tears [C]T using a simple kinetic model, and to examine whether [Cf] and [C]CSF can be predicted by [C]T using the resulting pharmacokinetic parameters."	( Assessment of tear concentrations on therapeutic drug monitoring. II. Pharmacokinetic analysis of valproic acid in guinea pig serum, cerebrospinal fluid, and tears. Honda, A; Kitagawa, S; Miyazaki, H; Nakajima, M; Sato, S; Shimada, K, 2001)	0.78
" The values of [C]CSF and [Cf] in the steady state can be represented by the following equations; [C]CSF = KINCSF/KOUTCSF x [Cf], [Cf] = KOUT/KINT x [C]T, and indicating that [Cf] and [C]CSF can be predicted by [C]T using the resulting pharmacokinetic parameters."	( Assessment of tear concentrations on therapeutic drug monitoring. II. Pharmacokinetic analysis of valproic acid in guinea pig serum, cerebrospinal fluid, and tears. Honda, A; Kitagawa, S; Miyazaki, H; Nakajima, M; Sato, S; Shimada, K, 2001)	0.53
"The measurement of [C]T which can be collected non-invasively and estimated the pharmacokinetic parameters for [Cf], [C]CSF, and [C]T might be a very useful method for TDM of VPA."	( Assessment of tear concentrations on therapeutic drug monitoring. II. Pharmacokinetic analysis of valproic acid in guinea pig serum, cerebrospinal fluid, and tears. Honda, A; Kitagawa, S; Miyazaki, H; Nakajima, M; Sato, S; Shimada, K, 2001)	0.53
" The plasma level decline was biphasic with a terminal half-life of 14."	( Pharmacokinetics of valproic acid in patients with bipolar disorder. Das, S; Goswami, U; Tayal, G; Vasudev, K, 2001)	0.63
" Apparent clearance (CL/F) and volume of distribution (V/F) were the pharmacokinetic parameters estimated."	( Population pharmacokinetics of lamotrigine. Chan, V; Ilett, KF; Morris, RG; Tett, SE, 2001)	0.31
" The peak concentration (Cmax) of CZP and the time intervals from dosing to Cmax (Tmax) were 20."	( Pharmacokinetic and pharmacodynamic effects of clonazepam in children with epilepsy treated with valproate: a preliminary study. Wang, L; Wang, XD, 2002)	0.31
"The aim of this study was to obtain a pharmacokinetic calculation for valproic acid (VPA) and its free fraction in 50 children and adolescents (4-18 years) treated for epilepsy in VPA monotherapy and bitherapy with carbamazepine (CBZ)."	( Studies on the pharmacokinetics of total and free valproate in mono- and bitherapy with carbamazepine in epileptic children and adolescents. Galas-Zgorzalewicz, B; Steinborn, B, 2002)	0.55
"To determine population-based pharmacokinetic parameters for intravenous valproic acid, and the factors influencing these parameters, in Korean adults."	( Population pharmacokinetics of intravenous valproic acid in Korean patients. Kang, SS; Kim, ON; Lee, SB; Lee, YB; Park, HM; Shin, DJ; Yim, DS, 2002)	0.81
"The novel antiepileptic drug (AED) levetiracetam (LEV; Keppra) has a wide therapeutic index and pharmacokinetic characteristics predicting limited drug-interaction potential."	( Levetiracetam, a new antiepileptic agent: lack of in vitro and in vivo pharmacokinetic interaction with valproic acid. Browne, TR; Coupez, R; Nicolas, JM, 2003)	0.53
" An open-label, one-way, one-sequence crossover clinical trial was conducted in 16 healthy volunteers to assess further the possibility of any relevant pharmacokinetic interaction."	( Levetiracetam, a new antiepileptic agent: lack of in vitro and in vivo pharmacokinetic interaction with valproic acid. Browne, TR; Coupez, R; Nicolas, JM, 2003)	0.53
"These findings suggest the absence of a pharmacokinetic interaction between VPA and LEV during short-term administration, and suggest that dose adjustment is not required when these two drugs are given together."	( Levetiracetam, a new antiepileptic agent: lack of in vitro and in vivo pharmacokinetic interaction with valproic acid. Browne, TR; Coupez, R; Nicolas, JM, 2003)	0.53
"The availability of an intravenous formulation now makes possible rapid administration of valproate (VPA) loading doses, but estimates of key VPA pharmacokinetic parameters in patients have limited the use of this approach."	( Valproate unbound fraction and distribution volume following rapid infusions in patients with epilepsy. Cao, G; Cloyd, JC; Collins, SD; Dutta, S; Granneman, GR; Walch, JK, 2003)	0.32
" administration of individual enantiomers to mice, with (R)-PID having lower clearance and longer half-life than (S)-PID."	( Characterization of the anticonvulsant profile and enantioselective pharmacokinetics of the chiral valproylamide propylisopropyl acetamide in rodents. Bennett, GD; Bialer, M; Blotnik, S; Finnell, RH; Isoherranen, N; Spiegelstein, O; White, HS; Wilcox, KS; Woodhead, JH; Yagen, B, 2003)	0.32
" There were no significant differences in the pharmacokinetic parameters of total CPT-11 between treatment groups (p>0."	( The modulation of irinotecan-induced diarrhoea and pharmacokinetics by three different classes of pharmacologic agents. Cheung, YB; Chowbay, B; Lee, EJ; Sharma, A; Zhou, QY, )	0.13
" In mice, VTD had five to 10 times lower clearance (CL), and three times longer half-life than I-VTD and DM-VTD, making it a more attractive compound than DM-VTD and I-VTD for further development."	( Anticonvulsant activity, teratogenicity and pharmacokinetics of novel valproyltaurinamide derivatives in mice. Bialer, M; Finnell, RH; Isoherranen, N; Merriweather, M; Spiegelstein, O; White, HS; Wlodarczyk, B; Woodhead, JH; Yagen, B, 2003)	0.32
" Such aggravation may be due to a variety of factors that include a paradoxical pharmacodynamic effect."	( Antiepileptic drug-induced pharmacodynamic aggravation of seizures: does valproate have a lower potential? Genton, P; Hirsch, E, 2003)	0.32
"Valproate exhibits a complex pharmacokinetic profile due to concentration-dependent protein binding and clearance."	( Dose-related pharmacokinetics and pharmacodynamics of valproate in the elderly. Felix, S; Hardy, BG; Naranjo, CA; Sproule, BA, 2003)	0.32
" Valproate's pharmacokinetic profile has been extensively studied, mostly within the context of treatment of epilepsy."	( Pharmacokinetics, drug interactions, and tolerability of valproate. DeVane, CL, 2003)	0.32
"This paper describes a developed pharmacokinetic model for the estimation of valproic acid (VPA) clearance (CL) calculated from routine clinical data taken from Egyptian epileptic patients."	( Pharmacokinetic modelling of valproic acid from routine clinical data in Egyptian epileptic patients. Cosson, V; EL Desoky, ES; EL Din Amry, S; Fuseau, E, 2004)	0.84
"The population pharmacokinetic model for VPA could be used for a priori recommendation and dose optimisation of that drug in the Egyptian population of epileptic patients."	( Pharmacokinetic modelling of valproic acid from routine clinical data in Egyptian epileptic patients. Cosson, V; EL Desoky, ES; EL Din Amry, S; Fuseau, E, 2004)	0.61
" Given the known pharmacokinetic interaction between these two drugs, clinically relevant questions that should be answered include (1) at what dose and/or concentration of VPA does this interaction begin, and (2) at what dose of VPA does maximal inhibition occur."	( Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetics: implications for conversion to lamotrigine monotherapy. Gidal, BE; Maloney, K; Parnell, J; Sale, M; Sheth, R, 2003)	0.32
" Serial blood samples were obtained over 120 h post-dose in order to calculate LTG kinetic parameters including area under the concentration-time curve, apparent oral clearance, elimination half-life and percent inhibition of LTG clearance at each dosage level of VPA."	( Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetics: implications for conversion to lamotrigine monotherapy. Gidal, BE; Maloney, K; Parnell, J; Sale, M; Sheth, R, 2003)	0.32
"LTG pharmacokinetic parameters were evaluated in adult healthy female & male volunteers."	( Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetics: implications for conversion to lamotrigine monotherapy. Gidal, BE; Maloney, K; Parnell, J; Sale, M; Sheth, R, 2003)	0.32
"To develop a population pharmacokinetic model to evaluate the effects of variety of covariates on clearance of carbamazepine (CBZ) and its main metabolite carbamazepine-10,11-epoxide (CBZE) in Chinese population."	( Population pharmacokinetic modeling of steady state clearance of carbamazepine and its epoxide metabolite from sparse routine clinical data. Jiao, Z; Shi, XJ; Zhao, ZG; Zhong, MK, 2004)	0.32
"Valproic acid pharmacokinetic profile and tolerability after administration of divalproex sodium extended-release tablets was characterized in older children and adolescents."	( Divalproex-ER pharmacokinetics in older children and adolescents. Biton, V; Conway, JM; Dutta, S; Kearns, GL; Reed, MD; Sallee, FR; Zhang, Y, 2004)	1.77
"On analysis, steady-state pharmacokinetic parameters (peak plasma concentrations [C(max)], time to C(max,) area under the concentration-time curve) of valproate were of the same order of magnitude on day 14 (monotherapy) and day 28 (valproate plus risperidone or placebo), with no period effect."	( Risperidone does not affect steady-state pharmacokinetics of divalproex sodium in patients with bipolar disorder. Alexander, J; Lacroix, D; Ravindran, A; Silverstone, P; van Schaick, E; Vermeulen, A, 2004)	0.32
" Pharmacokinetic parameters were determined by a noncompartmental method."	( Topiramate pharmacokinetics in children with epilepsy aged from 6 months to 4 years. Bouhours, P; Chiron, C; d'Athis, P; Dulac, O; Echenne, B; Grinspan, A; Mikaeloff, Y; Pons, G; Rey, E; Soufflet, C; Vallée, L, 2004)	0.32
" Valproic acid pharmacokinetic values were measured, and the safety of each regimen was evaluated."	( Pharmacokinetics and safety of extended-release divalproex sodium tablets: morning versus evening administration. Cavanaugh, JH; Dutta, S; Reed, RC, 2004)	1.23
"Using sparse data of valproate (VPA) serum concentrations to build a population pharmacokinetic (PPK) model of VPA in Chinese children with epilepsy and to predict serum concentrations for new patients using a Bayesian approach."	( Population pharmacokinetic model of valproate and prediction of valproate serum concentrations in children with epilepsy. Jiang, DC; Wang, L, 2004)	0.32
" Coadministration with lithium increased mean Cmax and AUC values of aripiprazole by about 19% and 15%, respectively, whereas the apparent oral clearance decreased by 15%."	( Pharmacokinetics of aripiprazole and concomitant lithium and valproate. Bark, N; Citrome, L; Josiassen, R; Mallikaarjun, S; Salazar, DE, 2005)	0.33
"To report a pharmacokinetic interaction between valproic acid (VPA) and anticancer agents observed in an epileptic patient."	( Pharmacokinetic interaction on valproic acid and recurrence of epileptic seizures during chemotherapy in an epileptic patient. Ikeda, H; Kihira, K; Murakami, T; Takano, M; Usui, T, 2005)	0.87
" Three pharmacokinetic profiles were obtained: on days -7 and -1, to assess pharmacokinetic parameters of oral valproic acid administered alone, and on day 35, after 14 days of zonisamide treatment at the maximal tolerated dose, to evaluate the effect of zonisamide on valproic acid pharmacokinetics and to characterise zonisamide pharmacokinetics in the presence of valproic acid."	( Lack of pharmacokinetic interactions between steady-state zonisamide and valproic acid in patients with epilepsy. Brodie, M; Grundy, JS; Levy, RH; Ragueneau-Majlessi, I; Shah, J; Smith, D, 2005)	0.77
"Seventeen patients completed the study, with 16 patients contributing to the pharmacokinetic analyses."	( Lack of pharmacokinetic interactions between steady-state zonisamide and valproic acid in patients with epilepsy. Brodie, M; Grundy, JS; Levy, RH; Ragueneau-Majlessi, I; Shah, J; Smith, D, 2005)	0.56
"Human pharmacokinetic parameters are often predicted prior to clinical study from in vivo preclinical pharmacokinetic data."	( Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure. Jolivette, LJ; Ward, KW, 2005)	0.33
" The pharmacokinetic and pharmacodynamic profiles of intravenous lorazepam were characterized before and after inhibition with 600 mg valproate once daily for 4 days and after induction with rifampin (INN, rifampicin) pretreatment (600 mg once daily for 10 days), with a washout period of 10 days between."	( Effect of the UGT2B15 genotype on the pharmacokinetics, pharmacodynamics, and drug interactions of intravenous lorazepam in healthy volunteers. Cho, JY; Chung, JY; Jang, IJ; Jung, HR; Kim, JR; Lim, KS; Shin, SG; Yu, KS, 2005)	0.33
"Carbapenem antibiotics cause pharmacokinetic interaction with valproic acid (VPA) in clinical pharmacotherapy."	( Increased erythrocyte distribution of valproic acid in pharmacokinetic interaction with carbapenem antibiotics in rat and human. Kiribayashi, Y; Maeda, Y; Murakami, T; Nagai, J; Omoda, K; Takano, M; Yumoto, R, 2005)	0.84
" VPA was not found to have any clinically significant influence on TPM pharmacokinetic and metabolic profiles."	( A comparative study of the effect of carbamazepine and valproic acid on the pharmacokinetics and metabolic profile of topiramate at steady state in patients with epilepsy. Bialer, M; Britzi, M; Doose, DR; Gatti, G; La Neve, A; Levy, RH; Maryanoff, BE; Mimrod, D; Perucca, E; Soback, S; Specchio, LM; Specchio, N, 2005)	0.58
"The aim of the study was to obtain pharmacokinetic data for carbamazepine (CBZ) and its fractions not bound with proteins in bitherapy with lamotrigine (LTG), topiramate (TPM), vigabatrin (VGB) or valproic acid (VPA) in children and adolescents treated for epilepsy."	( Pharmacokinetic interactions of carbamazepine with some antiepileptic drugs during epilepsy treatment in children and adolescents. Steinborn, B, 2005)	0.52
" For pharmacokinetic calculations of total and free CBZ, one-compartment model was used according to standardized procedure."	( Pharmacokinetic interactions of carbamazepine with some antiepileptic drugs during epilepsy treatment in children and adolescents. Steinborn, B, 2005)	0.33
"No significant differences in pharmacokinetic parameters of unbound CBZ in four groups of patients on bitherapy with CBZ and LTG, TPM, VGB or VPA were found."	( Pharmacokinetic interactions of carbamazepine with some antiepileptic drugs during epilepsy treatment in children and adolescents. Steinborn, B, 2005)	0.33
" Any pharmacokinetic contribution was ascertained by measurement of brain antiepileptic drug (AED) concentrations."	( Pharmacodynamic and/or pharmacokinetic characteristics of interactions between loreclezole and four conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice: an isobolographic analysis. Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2005)	0.33
" Likewise, PGB steady-state pharmacokinetic parameter values were similar among patients receiving CBZ, PHT, LTG, or VPA and, in general, were similar to those observed historically in healthy subjects receiving PGB alone."	( Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy. Alvey, CW; Bockbrader, HN; Brodie, MJ; Bron, NJ; Gibson, GL; Hounslow, NJ; Posvar, EL; Randinitis, EJ; Wesche, DL; Wilson, EA, 2005)	0.33
" We then determined the pharmacokinetic profiles of S-2-pentyl-4-pentynoic hydroxamic acid and of S-2-pentyl-4-pentynoic acid in mice."	( S-2-pentyl-4-pentynoic hydroxamic acid and its metabolite s-2-pentyl-4-pentynoic acid in the NMRI-exencephaly-mouse model: pharmacokinetic profiles, teratogenic effects, and histone deacetylase inhibition abilities of further valproic acid hydroxamates an Eikel, D; Hoffmann, K; Lampen, A; Nau, H; Zoll, K, 2006)	0.52
" The exact mechanism of this pharmacokinetic interaction is unknown, although several experimental studies have been carried out in animals."	( [Pharmacokinetic interaction between valproic acid and meropenem]. Balcells Ramírez, J; Cabañas Poy, MJ; Clemente Bautista, S; Hidalgo Albert, E; Oliveras Arenas, M; Padullés Zamora, N; Sala Piñol, F, 2006)	0.61
"The aims of this study were to define the relationship between total and unbound valproic acid (VPA) concentrations, to compare pharmacokinetic parameters of total and unbound VPA, and to determine the difference in pharmacokinetic parameters between the seizure-controlled and -uncontrolled groups."	( Pharmacokinetic parameters of total and unbound valproic acid and their relationships to seizure control in epileptic children. Panomvana Na Ayudhya, D; Suwanmanee, J; Visudtibhan, A, )	0.61
"Phenytoin dosing is critical in cancer patients as to decreased absorption secondary to chemotherapy-induced gastrointestinal toxicity, increased phenytoin metabolism in the liver secondary to chemotherapy, extreme patient profile that falls outside the predicted pharmacokinetic population, frequent hypoalbuminaemia and polydrug treatment."	( Interactions of serum albumin, valproic acid and carbamazepine with the pharmacokinetics of phenytoin in cancer patients. Beijnen, JH; Boogerd, W; Huitema, AD; Joerger, M; Schellens, JH; van der Sande, JJ, 2006)	0.62
" It showed a beneficial pharmacokinetic profile in rats, having a high oral bioavailability of 75% and satisfactory values of clearance and volume of distribution."	( Anticonvulsant activity, neural tube defect induction, mutagenicity and pharmacokinetics of a new potent antiepileptic drug, N-methoxy-2,2,3,3-tetramethylcyclopropane carboxamide. Bialer, M; Finnell, RH; Lamb, JG; Sobol, E; White, HS; Wlodarczyk, BJ; Yagen, B, 2007)	0.34
" Brain AED concentrations were also measured so as to ascertain any pharmacokinetic contribution to the pharmacodynamic interactions."	( Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis. Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2006)	0.33
" However, these interactions were complicated by changes in brain AED concentrations consequent to pharmacokinetic interactions."	( Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis. Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2006)	0.33
" However, these conclusions are confounded by the fact that STP is associated with significant pharmacokinetic interactions."	( Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis. Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2006)	0.33
"For many drugs, steady-state concentration-time profiles are often not optimally characterised by the intrinsic terminal elimination half-life for various reasons, including multiexponential disposition with minimal contribution of the terminal phase to steady-state exposure or use of controlled-release formulations with extended zero- or mixed zero-/first-order absorption."	( Functional half-life is a meaningful descriptor of steady-state pharmacokinetics of an extended-release formulation of a rapidly cleared drug : as shown by once-daily divalproex-ER. Dutta, S; Reed, RC, 2006)	0.33
" The t((1/2)F) values of valproic acid in adult hepatic enzyme-uninduced healthy subjects and enzyme-induced epilepsy patients were calculated from five pharmacokinetic studies in which divalproex-ER was administered once daily for 6-14 days."	( Functional half-life is a meaningful descriptor of steady-state pharmacokinetics of an extended-release formulation of a rapidly cleared drug : as shown by once-daily divalproex-ER. Dutta, S; Reed, RC, 2006)	0.64
"0 hours versus the expected elimination half-life of 12-16 hours in this population (including patients on valproic acid monotherapy); for induced patients, t((1/2)F) was 26."	( Functional half-life is a meaningful descriptor of steady-state pharmacokinetics of an extended-release formulation of a rapidly cleared drug : as shown by once-daily divalproex-ER. Dutta, S; Reed, RC, 2006)	0.55
" The pharmacokinetics of the 260 PB concentrations at a steady-state obtained from 79 patients was described with a one-compartment open pharmacokinetic model with first-order elimination."	( Population estimation of the effects of cytochrome P450 2C9 and 2C19 polymorphisms on phenobarbital clearance in Japanese. Goto, S; Ishitsu, T; Murata, T; Nakada, N; Nakagawa, K; Seo, T; Ueda, N, 2007)	0.34
" Serial samples of blood (n = 4) and CSF (n = 3) were obtained for pharmacokinetic studies of total and free VPA."	( Plasma and cerebrospinal fluid pharmacokinetics of valproic acid after oral administration in non-human primates. Berg, SL; Blaney, SM; Gibson, B; McGuffey, L; Ou, CN; Stapleton, SL; Thompson, PA, 2008)	0.6
"Pharmacokinetic and pharmacodynamic profiles of lorazepam and valproate were analyzed according to uridine 5'-diphosphate-glucuronosyltransferase (UGT)2B7 genotype in 14 healthy subjects with UGT2B15*2/*2 genotype."	( Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Cho, JY; Chung, JY; Jang, IJ; Kim, JR; Lim, KS; Shin, SG; Sohn, DR; Yu, KS, 2008)	0.58
"To determine whether there is a pharmacokinetic drug interaction between quetiapine fumarate and divalproex sodium."	( Open-label steady-state pharmacokinetic drug interaction study on co-administered quetiapine fumarate and divalproex sodium in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. Davis, PC; DeVane, CL; Ennis, DJ; Figueroa, C; Hamer-Maansson, JE; Smith, MA; Winter, HR, 2007)	0.34
"Combination therapy with quetiapine (150 mg bid) and divalproex (500 mg bid) resulted in small and statistically non-significant pharmacokinetic changes."	( Open-label steady-state pharmacokinetic drug interaction study on co-administered quetiapine fumarate and divalproex sodium in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. Davis, PC; DeVane, CL; Ennis, DJ; Figueroa, C; Hamer-Maansson, JE; Smith, MA; Winter, HR, 2007)	0.34
" Here, we report on the pharmacokinetic and pharmacodynamic effects of this combination in a cancer patient."	( Irinotecan chemotherapy during valproic acid treatment: pharmacokinetic interaction and hepatotoxicity. de Jong, FA; Kitzen, JJ; Loos, WJ; Mathijssen, RH; Mathôt, RA; van den Bent, MJ; van der Bol, JM; Verweij, J, 2007)	0.63
" Blood samples for pharmacokinetic purposes were drawn during a course with and a course without concomitant valproic acid."	( Irinotecan chemotherapy during valproic acid treatment: pharmacokinetic interaction and hepatotoxicity. de Jong, FA; Kitzen, JJ; Loos, WJ; Mathijssen, RH; Mathôt, RA; van den Bent, MJ; van der Bol, JM; Verweij, J, 2007)	0.84
"The aim of the present study is to establish a population pharmacokinetic (PPK) model of valproate (VPA) in Chinese epileptic children to promote the reasonable use of anti-epileptic drugs."	( Population pharmacokinetics of valproate in Chinese children with epilepsy. Bai, XR; Jiang, DC; Li, L; Lu, W; Wang, L; Wang, YQ, 2007)	0.34
" Patients continued on ER + 500 for 4 additional weeks after the pharmacokinetic phase."	( A pharmacokinetic and clinical evaluation of switching patients with bipolar I disorder from delayed-release to extended-release divalproex. Bartolucci, AA; Davis, LL; Li, X; Lowe, JS; Williford, RB, 2007)	0.34
"The aim of this study was to define a population pharmacokinetic model that could estimate the clearance of valproate (VPA) in a Serbian epileptic population."	( Pharmacokinetic modeling of valproate from clinical data in Serbian epileptic patients. Jankovic, SM; Milovanovic, JR, 2007)	0.34
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."	( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Lombardo, F; Obach, RS; Waters, NJ, 2008)	0.35
" There have been no previous studies designed to investigate a potential pharmacokinetic (PK) interaction between MCB and VPA or CBZ; however, these agents are likely to be used concomitantly for the treatment of depressive disorders."	( Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study. Miljkovic, B; Pokrajac, M; Rakic Ignjatovic, A; Timotijevic, I; Todorovic, D, 2009)	0.61
"The purpose of this study was to perform population pharmacokinetic (PPK) analysis on carbamazepine and to determine the population model of clearance of this drug in terms of individual patient characteristics."	( Pharmacokinetic modeling of carbamazepine based on clinical data from Serbian epileptic patients. Jankovic, SM; Jovanovic, D; Milovanovic, JR, 2008)	0.35
"To evaluate the effects of CYP2C19 and CYP2C9 genotypes on the pharmacokinetic variability of valproic acid (VPA) in epileptic patients using a population pharmacokinetic (PPK) approach."	( Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients: nonlinear mixed-effect modeling. Bai, X; Jiang, D; Li, L; Lu, W; Müller, M; Wang, Y; Zhang, Q, 2009)	0.8
" Pharmacokinetic parameters are necessary to predict the optimum therapeutic level after administration."	( Pharmacokinetics and clinical application of intravenous valproate in Thai epileptic children. Bhudhisawadi, K; Chulavatnatol, S; Kaojareon, S; Vaewpanich, J; Visudtibhan, A, 2011)	0.37
" Plural simultaneously - operant pharmacodynamic mechanisms may explain catatonia of unclear etiology and reconcile a seemingly contradictory literature (e."	( Catatonia and CPK elevation in neurosyphilis: role of plural pharmacodynamic mechanisms. Carter, WG; Lauterbach, EC; Norris, BK; Shillcutt, SD, 2009)	0.35
" Blood and tumor tissue were collected for determination of serum valproic acid concentration and evaluation of pharmacodynamic effects by immunofluorescence cytochemistry and immunohistochemistry."	( Phase I pharmacokinetic and pharmacodynamic evaluation of combined valproic acid/doxorubicin treatment in dogs with spontaneous cancer. Gustafson, DL; Thamm, DH; Wittenburg, LA, 2010)	0.83
" Comparative pharmacokinetic analysis showed that α-Cl-TMCD is less susceptible to liver first-pass effect than α-F-TMCD because of lower total (metabolic) clearance and liver extraction ratio."	( Comparative pharmacodynamic and pharmacokinetic analysis of two anticonvulsant halo derivatives of 2,2,3,3-tetramethylcyclopropanecarboxamide, an amide of a cyclic analog of valproic acid. Bialer, M; Finnell, RH; Hen, N; Kaufmann, D; Pessah, N; Wlodarczyk, B; Yagen, B, 2010)	0.55
"The aim of the present study was to build population pharmacokinetic models for the clearance of valproate (VPA) in 2 separate populations of Serbian patients with epilepsy, children and adults."	( Factors influencing valproate pharmacokinetics in children and adults. Jankovic, S; Jankovic, SM; Milovanovic, JR, 2010)	0.36
" The pharmacokinetic models obtained were validated in groups of 15 epileptic patients, each showing good predictive performance of the model."	( Factors influencing valproate pharmacokinetics in children and adults. Jankovic, S; Jankovic, SM; Milovanovic, JR, 2010)	0.36
"The aim of our study was to develop and use a population pharmacokinetic model for assessment of individual valproate clearance in children and young adults suffering from epilepsy."	( [Pharmacokinetic modelling of valproate in epileptic patients]. Jakovljević, MB; Janković, S; Janković, SM; Milovanović, JR; Todorović, N, )	0.13
" A validation set of 20 epileptic patients (one blood sample per a patient) was used to estimate predicted performances of the pharmacokinetic model."	( [Pharmacokinetic modelling of valproate in epileptic patients]. Jakovljević, MB; Janković, S; Janković, SM; Milovanović, JR; Todorović, N, )	0.13
" The patients' characteristics and pharmacokinetic parameters were compared between the 2 dosage groups using independent t test or χ² test where appropriate."	( The impact of dosage of sustained-release formulation on valproate clearance and plasma concentration in psychiatric patients: analysis based on routine therapeutic drug monitoring data. Chamchitchun, S; Panomvana, D; Silpakit, O; Sriboonruang, T, 2011)	0.37
"Extractive electrospray ionization mass spectrometry is shown to allow real-time, in vivo drug monitoring and pharmacokinetic measurement in a non-invasive, pain-free manner as demonstrated by the mass spectral measurement of a novel exhaled breath biomarker for valproic acid, a medication used to control epilepsy."	( Real-time, in vivo monitoring and pharmacokinetics of valproic acid via a novel biomarker in exhaled breath. Azov, V; Chen, H; Chingin, K; Disko, A; Gamez, G; Krämer, G; Zenobi, R; Zhu, L, 2011)	0.8
"Most of bayesian pharmacokinetic studies and the influence of clinical variables have been carried out in adults."	( Effect of treatment and additional disease on pharmacokinetic of valproic acid in children with epilepsy. Flores Pérez, J; Flores-Murrieta, F; Juárez-Olguín, H; Lares Asseff, I; Lugo-Goytia, G; Ruiz-García, M, )	0.37
"The aim was to estimate population-based pharmacokinetic of valproic acid (VPA) and to determine the effect of treatment and additional disease on its performance in children with epilepsy."	( Effect of treatment and additional disease on pharmacokinetic of valproic acid in children with epilepsy. Flores Pérez, J; Flores-Murrieta, F; Juárez-Olguín, H; Lares Asseff, I; Lugo-Goytia, G; Ruiz-García, M, )	0.61
"Based on a population model of children with epilepsy, the pharmacokinetic of VPA could be altered by weight, age and the administration of CBZ and additional GER to epilepsy."	( Effect of treatment and additional disease on pharmacokinetic of valproic acid in children with epilepsy. Flores Pérez, J; Flores-Murrieta, F; Juárez-Olguín, H; Lares Asseff, I; Lugo-Goytia, G; Ruiz-García, M, )	0.37
" On the other hand, pharmacokinetic analyses revealed that joint EPA administration had no effect on serum VPA concentrations."	( Eicosapentaenoic acid ablates valproate-induced liver oxidative stress and cellular derangement without altering its clearance rate: dynamic synergy and therapeutic utility. Abdel-Aziz, A; Abdel-Dayem, MA; El-Azab, MF; El-Mowafy, AM; Said, SA, )	0.13
"Two open-label, randomized, multiple-dose clinical studies evaluated the potential for pharmacokinetic interaction between the antiepileptic drugs lacosamide and valproic acid."	( No pharmacokinetic interaction between lacosamide and valproic acid in healthy volunteers. Bonn, R; Cawello, W, 2012)	0.82
" The validity of this approach remains uncertain and could be improved by understanding sources of pharmacokinetic variability."	( Population pharmacokinetics of valproic acid in pediatric patients with epilepsy: considerations for dosing spinal muscular atrophy patients. Barrett, JS; Jayaraman, B; Swoboda, KJ; Williams, JH, 2012)	0.66
"In the first DDI study, coadministration of ketoconazole (a CYP3A4 inhibitor) and clobazam increased clobazam's area under the concentration time curve from time zero extrapolated to infinity (AUC(0-∞) ) 54% and decreased clobazam's maximum plasma concentration (C(max) ) by 15% versus administration of clobazam alone, but the combination affected these pharmacokinetic parameters for N-CLB to a lesser degree."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
" UGT polymorphisms had no influence on the pharmacokinetic interactions between carbamazepine and VPA."	( Influence of UDP-glucuronosyltransferase polymorphisms on valproic acid pharmacokinetics in Chinese epilepsy patients. Chu, XM; Hao, HP; Wang, GJ; Zhang, LF; Zhang, SN; Zhou, JH, 2012)	0.62
" Consequences of these pharmacokinetic (PK) properties may include adverse events (AEs) and breakthrough seizures, potentially leading to poor adherence."	( Extended-release antiepileptic drugs: a comparison of pharmacokinetic parameters relative to original immediate-release formulations. Hovinga, CA; Leppik, IE, 2013)	0.39
" Cosinor analysis showed circadian rhythm in different pharmacokinetic parameters."	( Circadian variation of Valproic acid pharmacokinetics in mice. Aouam, K; Ben-Attia, M; Ben-Cherif, W; Boughattas, NA; Dridi, I; Reinberg, A, 2013)	0.7
" The elimination half-life (t ½ = 40."	( The effect of uridine diphosphate glucuronosyltransferase (UGT)1A6 genetic polymorphism on valproic acid pharmacokinetics in Indian patients with epilepsy: a pharmacogenetic approach. Arumugam, K; Behari, M; Jain, DC; Mallayasamy, SR; Munisamy, M; Raghavan, S; Rajakannan, T; Ramanujam, B; Subbiah, V; Tripathi, M, 2013)	0.61
" A population pharmacokinetic analysis with sex, weight, age and contraceptive therapy as possible covariates was performed."	( Sex related differences on valproic acid pharmacokinetics after oral single dose. Derendorf, H; Fagiolino, P; Ibarra, M; Vázquez, M, 2013)	0.69
" This study describes synthesis and stereospecific comparative pharmacodynamics (PD, anticonvulsant activity and teratogenicity) and pharmacokinetic (PK) analysis of four individual SPD stereoisomers."	( Stereoselective pharmacodynamic and pharmacokinetic analysis of sec-Butylpropylacetamide (SPD), a new CNS-active derivative of valproic acid with unique activity against status epilepticus. Bialer, M; Finnell, RH; Hen, N; McDonough, JH; Shekh-Ahmad, T; Wlodarczyk, B; Yagen, B, 2013)	0.6
"To establish using dried blood spot (DBS) as a surrogate to plasma for therapeutic drug monitoring (TDM) of carbamazepine (CBZ), we compared the population pharmacokinetic (PPK) estimates from concurrent DBS and plasma levels."	( Estimation and comparison of carbamazepine population pharmacokinetics using dried blood spot and plasma concentrations from people with epilepsy: the clinical implication. Chan, E; Ho, PC; Kong, ST; Lim, SH, 2014)	0.4
"To determine the effects of CYP3A5 polymorphisms on carbamazepine (CBZ) pharmacokinetic parameters when CBZ is used either as monotherapy or co-administered with phenytoin (PHT), phenobarbital (PB) or valproic acid (VPA)."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.78
" Pharmacokinetic parameters of CBZ; clearance and dose-adjusted CBZ levels in patients with different genotypes were calculated and compared."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.59
"The LTG population pharmacokinetic model developed in this study may be a reliable method for individualising the LTG dosing regimen in paediatric and young adult patients on combination therapy during therapeutic drug monitoring."	( Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients--nonlinear mixed effects modelling approach. Brzaković, B; Kovačević, SV; Martinović, Ž; Miljković, B; Pokrajac, M; Prostran, M; Vučićević, K, 2014)	0.4
"Pharmacotherapy for mood disorders during pregnancy is often complicated by pregnancy-related pharmacokinetic changes and the need for dose adjustments."	( Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. Byatt, N; Deligiannidis, KM; Freeman, MP, 2014)	0.4
"The English-language literature indexed on MEDLINE/PubMed was searched for original observational studies (controlled and uncontrolled, prospective and retrospective), case reports, and case series that evaluated or described pharmacokinetic changes or TDM during pregnancy or the postpartum period."	( Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. Byatt, N; Deligiannidis, KM; Freeman, MP, 2014)	0.4
"Substantial pharmacokinetic changes can occur during pregnancy in a number of commonly used antidepressants and mood stabilizers."	( Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. Byatt, N; Deligiannidis, KM; Freeman, MP, 2014)	0.4
"There are several reports describing population pharmacokinetic (PPK) models of valproic acid (VPA)."	( Population pharmacokinetics of valproic acid in adult Chinese epileptic patients and its application in an individualized dosage regimen. Guo, XZ; Huang, PF; Jiao, Z; Lin, WW; Liu, YW; Ma, CL; Wang, CL; Wang, HY, 2015)	0.93
" The aim of this work was to develop a physiologically based pharmacokinetic model for plasma and tissue/organ prediction in children and adults following intravenous and oral dosing of Valproic acid."	( A physiologically based pharmacokinetic model for Valproic acid in adults and children. Aarons, L; Ogungbenro, K, 2014)	0.85
" However, this is the first case of VPA-induced hearing loss that was tested and confirmed with a VPA rechallenge, supported by serial audiometry and pharmacokinetic modelling."	( Valproate-induced reversible sensorineural hearing loss: a case report with serial audiometry and pharmacokinetic modelling during a valproate rechallenge. Bakar, MZ; Lim, KS; Lo, YL; Tan, CT; Yeap, LL, 2014)	0.4
"This retrospective study included 237 and 169 VPA-treated Japanese patients with epilepsy for population pharmacokinetic and pharmacokinetic-pharmacodynamic analyses, respectively."	( Impact of the superoxide dismutase 2 Val16Ala polymorphism on the relationship between valproic acid exposure and elevation of γ-glutamyltransferase in patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis. Deguchi, M; Ishitsu, T; Kaneko, S; Nakagaswa, K; Nakashima, H; Nishimura, M; Noai, M; Ogusu, N; Oniki, K; Saruwatari, J; Yasui-Furukori, N, 2014)	0.63
"The present study aimed to establish population pharmacokinetic model for phenobarbital (PB), examining and quantifying the magnitude of PB interactions with other antiepileptic drugs concomitantly used and to demonstrate its use for individualization of PB dosing regimen in adult epileptic patients."	( Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients. Golubović, B; Jovanović, M; Kovačević, SV; Martinović, Ž; Miljković, B; Prostran, M; Vučićević, K, 2015)	0.42
"Valproic acid (VPA) follows a non-linear pharmacokinetic profile in terms of protein-binding saturation."	( A population pharmacokinetic model of valproic acid in pediatric patients with epilepsy: a non-linear pharmacokinetic model based on protein-binding saturation. Ding, J; Jiao, Z; Li, X; Lin, W; Miao, L; Wang, C; Wang, Y; Zhao, L; Zhao, Z, 2015)	2.13
" The population pharmacokinetic model was developed using NONMEM(®) software."	( A population pharmacokinetic model of valproic acid in pediatric patients with epilepsy: a non-linear pharmacokinetic model based on protein-binding saturation. Ding, J; Jiao, Z; Li, X; Lin, W; Miao, L; Wang, C; Wang, Y; Zhao, L; Zhao, Z, 2015)	0.69
" Furthermore, the proposed population pharmacokinetic model of VPA can be used to design rational dosage regimens to achieve desirable serum concentrations."	( A population pharmacokinetic model of valproic acid in pediatric patients with epilepsy: a non-linear pharmacokinetic model based on protein-binding saturation. Ding, J; Jiao, Z; Li, X; Lin, W; Miao, L; Wang, C; Wang, Y; Zhao, L; Zhao, Z, 2015)	0.69
"Thirty-five children with epilepsy were included in a prospective population pharmacokinetic study (using NONMEM(®) software)."	( Pharmacokinetics of clobazam and N-desmethylclobazam in children with dravet syndrome receiving concomitant stiripentol and valproic Acid. Chhun, S; Chiron, C; Dulac, O; Jullien, V; Pons, G; Rey, E; Tod, M, 2015)	0.62
"This is the first simultaneous pharmacokinetic model for clobazam and N-CLB in epileptic children."	( Pharmacokinetics of clobazam and N-desmethylclobazam in children with dravet syndrome receiving concomitant stiripentol and valproic Acid. Chhun, S; Chiron, C; Dulac, O; Jullien, V; Pons, G; Rey, E; Tod, M, 2015)	0.62
"Noninvasive, real-time pharmacokinetic (PK) monitoring of ketamine, propofol, and valproic acid, and their metabolites was achieved in mice, using secondary electrospray ionization and high-resolution mass spectrometry."	( Drug Pharmacokinetics Determined by Real-Time Analysis of Mouse Breath. Bregy, L; Brown, SA; Dallmann, R; Detmar, M; Hollmén, M; Kohler, M; Li, X; Martinez-Lozano Sinues, P; Proulx, S; Zenobi, R, 2015)	0.64
" Pharmacokinetic parameters were calculated using noncompartmental methods."	( Effects of amoxicillin/clavulanic acid on the pharmacokinetics of valproic acid. Huh, W; Jung, JA; Kim, JR; Ko, JW; Lee, SY; Yoo, HM, 2015)	0.65
" In this study, we developed a population-based pharmacokinetic (PK)-pharmacodynamic (PD) model to determine the optimal concentration of VPA according to the clinical characteristics of each patient."	( Determination of the Optimal Concentration of Valproic Acid in Patients with Epilepsy: A Population Pharmacokinetic-Pharmacodynamic Analysis. Ishitsu, T; Matsuda, K; Nakagawa, K; Nakashima, H; Nishimura, M; Ogusu, N; Oniki, K; Ono, T; Saruwatari, J; Shimomasuda, M; Yasui-Furukori, N, 2015)	0.68
" Therapeutic response, common adverse effects, and the pharmacokinetic profile of valproic acid were evaluated."	( Pharmacokinetics and Clinical Utility of Valproic Acid Administered via Continuous Infusion. Albuja, AC; Baumann, RJ; Bensalem-Owen, M; Cook, AM; Kapoor, S; Mathias, S; Stewart, AM; Zafar, MS, 2016)	0.93
" The relatively short half-life seen with intermittent intravenous bolus doing may lead to serum concentration variability."	( Steady-state pharmacokinetic simulation of intermittent vs. continuous infusion valproic acid therapy in non-critically ill and critically ill patients. Cook, AM; Van Matre, ET, 2016)	0.66
" Pharmacokinetic parameters were reviewed for 234 patients (25 critically ill) and compared between the two groups (non-critically ill vs."	( Steady-state pharmacokinetic simulation of intermittent vs. continuous infusion valproic acid therapy in non-critically ill and critically ill patients. Cook, AM; Van Matre, ET, 2016)	0.66
" Continuous infusion VPA provides more consistent serum steady-state concentrations while mitigating pharmacokinetic variability."	( Steady-state pharmacokinetic simulation of intermittent vs. continuous infusion valproic acid therapy in non-critically ill and critically ill patients. Cook, AM; Van Matre, ET, 2016)	0.66
" The purpose of the study was to investigate 2-way pharmacokinetic interactions between ESL and other AEDs as compared to OXC and CBZ."	( The Impact of Pharmacokinetic Interactions With Eslicarbazepine Acetate Versus Oxcarbazepine and Carbamazepine in Clinical Practice. Baftiu, A; Brodtkorb, E; Burns, ML; Dinarevic, J; Johannessen Landmark, C; Johannessen, SI; Kufaas, RF; Reimers, A; Svendsen, T, 2016)	0.43
"Possible pharmacokinetic interactions have been studied for ESL as compared to OXC and CBZ."	( The Impact of Pharmacokinetic Interactions With Eslicarbazepine Acetate Versus Oxcarbazepine and Carbamazepine in Clinical Practice. Baftiu, A; Brodtkorb, E; Burns, ML; Dinarevic, J; Johannessen Landmark, C; Johannessen, SI; Kufaas, RF; Reimers, A; Svendsen, T, 2016)	0.43
" The objective of the study was to identify pharmacokinetic interactions of different mood stabilizers on the metabolism of risperidone (RIS) under natural conditions."	( Pharmacokinetic Drug-Drug Interactions of Mood Stabilizers and Risperidone in Patients Under Combined Treatment. Gründer, G; Haen, E; Hiemke, C; Lammertz, SE; Paulzen, M; Schoretsanitis, G; Schruers, KR; Stegmann, B, 2016)	0.43
"The data give evidence for pharmacokinetic interactions between RIS and different anticonvulsant mood stabilizers."	( Pharmacokinetic Drug-Drug Interactions of Mood Stabilizers and Risperidone in Patients Under Combined Treatment. Gründer, G; Haen, E; Hiemke, C; Lammertz, SE; Paulzen, M; Schoretsanitis, G; Schruers, KR; Stegmann, B, 2016)	0.43
" The aim of this study was to try to build a population pharmacokinetic model that would describe the time course of VPA and its selected metabolites when the drug is ingested in an overdose situation."	( Population pharmacokinetic modelling of valproic acid and its selected metabolites in acute VPA poisoning. Jawień, W; Kłys, M; Piekoszewski, W; Wilimowska, J, 2017)	0.72
" For population pharmacokinetic evaluation of VPA and its metabolites, the two-compartment-model was applied."	( Population pharmacokinetic modelling of valproic acid and its selected metabolites in acute VPA poisoning. Jawień, W; Kłys, M; Piekoszewski, W; Wilimowska, J, 2017)	0.72
"The aims of the study were to develop a population pharmacokinetic model of orally administered brivaracetam in paediatric patients and to provide dosing suggestions."	( Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years. Schoemaker, R; Stockis, A; Wade, JR, 2017)	0.46
" Pharmacokinetic analysis was performed using non-linear mixed effects modelling, and a stepwise covariate search was used to determine factors influencing brivaracetam clearance."	( Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years. Schoemaker, R; Stockis, A; Wade, JR, 2017)	0.46
" Pharmacokinetic parameters were estimated using non-compartmental analysis."	( Plasma and cerebrospinal fluid pharmacokinetics of select chemotherapeutic agents following intranasal delivery in a non-human primate model. Cruz, R; Figg, WD; League-Pascual, JC; Lester-McCully, CM; Peer, CJ; Rodgers, L; Ronner, L; Shandilya, S; Warren, KE, 2017)	0.46
"This study characterized the population pharmacokinetic properties of valproic acid in patients with mania and determined potential factors that affect the pharmacokinetic properties of valproic acid in this population."	( Population Pharmacokinetics of Valproic Acid in Patients with Mania: Implication for Individualized Dosing Regimens. Methaneethorn, J, 2017)	0.97
"A qualified population pharmacokinetic model for valproic acid in patients with mania was developed."	( Population Pharmacokinetics of Valproic Acid in Patients with Mania: Implication for Individualized Dosing Regimens. Methaneethorn, J, 2017)	1
"The purpose was to investigate pharmacokinetic variability of valproic acid (VPA) in women of childbearing age by therapeutic drug monitoring (TDM) data to elucidate the variable relationship between dose and serum concentrations with the ultimate aim of facilitating safer use of VPA."	( Pharmacokinetic variability of valproate in women of childbearing age. Baftiu, A; Burns, ML; Farmen, AH; Johannessen Landmark, C; Johannessen, SI; Lossius, MI; Tomson, T, 2017)	0.7
" Serum levels of valproate were estimated using HPLC for pharmacokinetic study."	( Pharmacokinetic and pharmacodynamic interaction of hydroalcoholic extract of Ocimum sanctum with valproate. Gupta, YK; Joshi, D; Kaleekal, T; Kumar, R; Sarangi, SC, 2017)	0.46
"Valproic acid (VPA) is an older first-line antiepileptic drug with a complex pharmacokinetic (PK) profile, currently under investigation for several novel neurologic and non-neurologic indications."	( Physiologically based pharmacokinetic modeling of disposition and drug-drug interactions for valproic acid and divalproex. Alam, HB; Conner, TM; Georgoff, PE; Nikolian, VC; Pai, MP; Reed, RC; Sun, D; Zhang, T, 2018)	2.14
" The aims of this systematic review are to provide knowledge concerning population pharmacokinetics of valproic acid (VPA) and to identify factors influencing VPA pharmacokinetic variability."	( A systematic review of population pharmacokinetics of valproic acid. Methaneethorn, J, 2018)	0.94
" All population pharmacokinetic studies of VPA conducted in humans and that employed a nonlinear mixed effect modelling approach were included in this review."	( A systematic review of population pharmacokinetics of valproic acid. Methaneethorn, J, 2018)	0.73
"The aims of this study were to develop a population pharmacokinetic (PPK) model of lamotrigine (LTG) in Chinese epileptic children by using nonlinear mixed effects modeling (NONMEM) and to investigate the effects of valproic acid (VPA) and genetic polymorphisms of the major metabolizing enzymes (UGT1A4, UGT2B7) on the pharmacokinetics of LTG."	( Population pharmacokinetics of lamotrigine co-administered with valproic acid in Chinese epileptic children using nonlinear mixed effects modeling. Chen, Y; Liu, L; Liu, M; Liu, S; Lu, T; Wang, H; Xu, S; Zhao, L; Zhao, M, 2018)	0.91
" The purpose of this study was to characterise pharmacokinetic variability of VPA in pregnancy, and discuss use of therapeutic drug monitoring (TDM) as guidance to exposure in women."	( Pharmacokinetic variability of valproate during pregnancy - Implications for the use of therapeutic drug monitoring. Baftiu, A; Burns, ML; Farmen, AH; Johannessen Landmark, C; Johannessen, SI; Lossius, MI; Tomson, T, 2018)	0.48
"There is pronounced pharmacokinetic variability of VPA during pregnancy."	( Pharmacokinetic variability of valproate during pregnancy - Implications for the use of therapeutic drug monitoring. Baftiu, A; Burns, ML; Farmen, AH; Johannessen Landmark, C; Johannessen, SI; Lossius, MI; Tomson, T, 2018)	0.48
" The population pharmacokinetic (PPK) model was developed using a nonlinear mixed effects modelling (NONMEM) approach."	( Population pharmacokinetics of valproic acid in epileptic children: Effects of clinical and genetic factors. Chen, Y; Guo, Y; Wang, Z; Xu, S; Zhao, L; Zhao, M, 2018)	0.77
" Therefore, this study aimed to establish a population pharmacokinetic (PPK) model of LTG in Chinese children with epilepsy and to comprehensively evaluate the effects of genetic variations in drug-metabolizing enzymes, transporters, and a transcriptional regulator on LTG pharmacokinetics."	( A Population Pharmacokinetic-Pharmacogenetic Model of Lamotrigine in Chinese Children With Epilepsy. Chen, Y; Lu, T; Wang, H; Wang, Z; Xu, S; Zhao, L; Zhao, M, 2018)	0.48
" The aims of this study were to review all published valproate population pharmacokinetic models in children and assess them by external validation to determine their predictive performance."	( Simulations of Valproate Doses Based on an External Evaluation of Pediatric Population Pharmacokinetic Models. Aboura, R; Benaboud, S; Billette de Villemeur, T; Bouazza, N; Chenevier-Gobeaux, C; Desguerre, I; Freihuber, C; Gana, I; Hirt, D; Nabbout, R; Tauzin, M; Tréluyer, JM; Zheng, Y, 2019)	0.51
"Background Valproic acid is one of several antiepileptic medications requiring therapeutic drug monitoring due to its complex and wide pharmacokinetic interindividual variability."	( Estimation of apparent clearance of valproic acid in adult Saudi patients. Alandas, N; Alqahtani, S; Alsultan, A, 2019)	1.18
" Pharmacokinetic parameters of lithium and valproate, including maximum plasma concentration and area under the plasma concentration-time curve over a 12-h dosing interval, were calculated."	( Combination of Olanzapine and Samidorphan Has No Clinically Significant Effect on the Pharmacokinetics of Lithium or Valproate. Graham, C; Sun, L; von Moltke, L; Yagoda, S; Yao, B, 2020)	0.56
"This narrative review aimed to provide critical findings of the available literature about the role of pharmacodynamic AEDs' interactions in patients whose epilepsies were treated with polytherapy."	( Pharmacodynamic interactions of antiepileptic drugs: From bench to clinical practice. Brigo, F; Lattanzi, S; Verrotti, A; Zaccara, G, 2020)	0.56
"Electronic databases, Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica dataBASE (EMBASE), were systematically searched to identify relevant studies on pharmacodynamic AEDs' interactions in patients with epilepsy."	( Pharmacodynamic interactions of antiepileptic drugs: From bench to clinical practice. Brigo, F; Lattanzi, S; Verrotti, A; Zaccara, G, 2020)	0.56
" Conversely, the combination of AEDs may cause pharmacodynamic synergistic effects that may result in not only increased efficacy but also more adverse effects."	( Pharmacodynamic interactions of antiepileptic drugs: From bench to clinical practice. Brigo, F; Lattanzi, S; Verrotti, A; Zaccara, G, 2020)	0.56
" Both the safety and the pharmacokinetic populations of the stiripentol arm comprised 14 patients (2 placebo; 12 cannabidiol)."	( A Phase II Randomized Trial to Explore the Potential for Pharmacokinetic Drug-Drug Interactions with Stiripentol or Valproate when Combined with Cannabidiol in Patients with Epilepsy. Arenas Cabrera, CM; Ben-Menachem, E; Critchley, D; Crockett, J; Gunning, B; Morrison, G; Tayo, B; Toledo, M; VanLandingham, K; Wray, L, 2020)	0.56
"To evaluate external predictability of a population pharmacokinetic model of valproic acid in Thai patients with mania to ensure its appropriateness for use in other clinical settings."	( External evaluation of a published population pharmacokinetic model of valproic acid in Thai manic patients. Lohitnavy, M; Methaneethorn, J, 2020)	1.02
"The published population pharmacokinetic model was evaluated for its predictive ability (at both individual and population levels) and its precision by means of mean absolute prediction error (MAPE), root mean square error (RMSE) and normalised prediction distribution error (NPDE)."	( External evaluation of a published population pharmacokinetic model of valproic acid in Thai manic patients. Lohitnavy, M; Methaneethorn, J, 2020)	0.79
"The predictability of the population pharmacokinetic model of valproic acid in Thai patients with mania was confirmed."	( External evaluation of a published population pharmacokinetic model of valproic acid in Thai manic patients. Lohitnavy, M; Methaneethorn, J, 2020)	1.03
" We aimed an observational study to develop a population pharmacokinetic model for quantitative evaluation of the factors that influence lamotrigine pharmacokinetics in Mexican adults with epilepsy."	( Dosing Recommendations Based on Population Pharmacokinetics of Lamotrigine in Mexican Adult Patients With Epilepsy. Chávez-Castillo, CE; Medellín-Garibay, SE; Milán-Segovia, RDC; Rodríguez-Leyva, I; Romano-Moreno, S, 2020)	0.56
" The aim was to use long-term TDM to investigate pharmacokinetic variability of ASMs in these patients."	( Pharmacokinetic Variability During Long-Term Therapeutic Drug Monitoring of Valproate, Clobazam, and Levetiracetam in Patients With Dravet Syndrome. Bjørnvold, M; Burns, ML; Heger, K; Johannessen Landmark, C; Johannessen, SI; Lund, C; Sætre, E, 2020)	0.56
" Pharmacokinetic variability of the total number of measurements of valproate (n = 417), clobazam and N-desmethylclobazam (n = 328), and levetiracetam (n = 238) was determined."	( Pharmacokinetic Variability During Long-Term Therapeutic Drug Monitoring of Valproate, Clobazam, and Levetiracetam in Patients With Dravet Syndrome. Bjørnvold, M; Burns, ML; Heger, K; Johannessen Landmark, C; Johannessen, SI; Lund, C; Sætre, E, 2020)	0.56
" Pharmacokinetic variability and interactions can thus be identified and adjusted to facilitate decision making to achieve the optimal treatment outcome."	( Pharmacokinetic Variability During Long-Term Therapeutic Drug Monitoring of Valproate, Clobazam, and Levetiracetam in Patients With Dravet Syndrome. Bjørnvold, M; Burns, ML; Heger, K; Johannessen Landmark, C; Johannessen, SI; Lund, C; Sætre, E, 2020)	0.56
"This prospective study aimed to establish the valproic acid (VPA) population pharmacokinetic model in Chinese patients and realise personalised medication on the basis of population pharmacokinetics."	( Impact of gender, albumin, and CYP2C19 polymorphisms on valproic acid in Chinese patients: a population pharmacokinetic model. Guo, J; Guo, Z; Han, H; Huo, Y; Li, F; Li, Y; Zhou, Y, 2020)	1.06
" Nonlinear mixed-effect modelling was used to build the population pharmacokinetic model."	( Impact of gender, albumin, and CYP2C19 polymorphisms on valproic acid in Chinese patients: a population pharmacokinetic model. Guo, J; Guo, Z; Han, H; Huo, Y; Li, F; Li, Y; Zhou, Y, 2020)	0.8
" NONMEM software was used for population pharmacokinetic modeling."	( Population pharmacokinetics of unbound valproic acid in pediatric epilepsy patients in China: a protein binding model. Gu, X; Hu, Y; Jiao, Z; Li, Z; Ma, M; Peng, Q; Sheng, C; Yu, S; Zhou, B; Zhu, M, 2021)	0.89
"A one-compartment model of first-order absorption and first-order elimination was used to describe the pharmacokinetic characteristics of unbound VPA, and the linear non-saturable binding equation was introduced to describe the protein binding."	( Population pharmacokinetics of unbound valproic acid in pediatric epilepsy patients in China: a protein binding model. Gu, X; Hu, Y; Jiao, Z; Li, Z; Ma, M; Peng, Q; Sheng, C; Yu, S; Zhou, B; Zhu, M, 2021)	0.89
"We developed a population pharmacokinetic model of unbound and bound VPA that took account of protein binding."	( Population pharmacokinetics of unbound valproic acid in pediatric epilepsy patients in China: a protein binding model. Gu, X; Hu, Y; Jiao, Z; Li, Z; Ma, M; Peng, Q; Sheng, C; Yu, S; Zhou, B; Zhu, M, 2021)	0.89
" The alterations in pharmacokinetic parameters (maximum serum concentration, area under the curve, clearance) of AEDs were also found with co-administration of HECA."	( Pharmacodynamic and pharmacokinetic interactions of hydroalcoholic leaf extract of Centella asiatica with valproate and phenytoin in experimental models of epilepsy in rats. Agarwal, A; Arora, R; Ganeshan N, S; Gupta, YK; Kaleekal, T; Kumar, R; Sarangi, SC, 2021)	0.62
" But, alteration in pharmacokinetic parameters revel that needs critical medical supervision to avoid any toxic reactions."	( Pharmacodynamic and pharmacokinetic interactions of hydroalcoholic leaf extract of Centella asiatica with valproate and phenytoin in experimental models of epilepsy in rats. Agarwal, A; Arora, R; Ganeshan N, S; Gupta, YK; Kaleekal, T; Kumar, R; Sarangi, SC, 2021)	0.62
" The objective of this work was to evaluate predictive performance of two early concentrations and prior pharmacokinetic (PK) information for estimating early exposure."	( A pharmacokinetic simulation study to assess the performance of a sparse blood sampling approach to quantify early drug exposure. Brundage, RC; Chamberlain, JM; Cloyd, JC; Coles, LD; Elm, JJ; Ivaturi, V; Kapur, J; Sathe, AG; Silbergleit, R, 2021)	0.62
" Pharmacokinetic drug-drug interactions (DDIs) between antiseizure medications (ASMs) and anti-infectives can occur and influence their efficacy or cause toxicity."	( A review of pharmacokinetic drug interactions between antimicrobial and antiseizure medications in children. Lattanzi, S; Zaccara, G, 2021)	0.62
"In this study, we examined whether the pharmacokinetic profiles of sodium valproate (SVA), levetiracetam (LEV), and carbamazepine (CBZ) are affected by altering the dosing time of RACOL®-NF Semi Solid for Enteral Use (RASS), a prescribed semi-solid formula."	( Effects of concurrent and staggered dosing of semi-solid enteral nutrients on pharmacokinetic behavior of antiepileptic drugs after oral administration in rats. Fukuno, S; Hatsuda, Y; Iwanami, Y; Konishi, H; Myotoku, M; Nagai, K; Omotani, S; Ryuno, Y, 2021)	0.62
"There was no difference in pharmacokinetic characteristics of SVA and LEV when the dosing time of RASS was altered."	( Effects of concurrent and staggered dosing of semi-solid enteral nutrients on pharmacokinetic behavior of antiepileptic drugs after oral administration in rats. Fukuno, S; Hatsuda, Y; Iwanami, Y; Konishi, H; Myotoku, M; Nagai, K; Omotani, S; Ryuno, Y, 2021)	0.62
"We concluded that the pharmacokinetic profiles of CBZ, but not SVA and LEV, after its oral administration are affected by the dosing time of RASS, but staggered administration of CBZ and RASS prevented their interaction."	( Effects of concurrent and staggered dosing of semi-solid enteral nutrients on pharmacokinetic behavior of antiepileptic drugs after oral administration in rats. Fukuno, S; Hatsuda, Y; Iwanami, Y; Konishi, H; Myotoku, M; Nagai, K; Omotani, S; Ryuno, Y, 2021)	0.62
"Individual levetiracetam pharmacokinetic parameters were calculated based on therapeutic drug monitoring data, using a one-compartmental model, and regression models were used to explore possible covariates."	( Levetiracetam pharmacokinetics and its covariates: proposal for optimal dosing in the paediatric population. Pokorná, P; Šíma, M; Slanař, O; Švestková, N, 2023)	0.91
"This study reviewed all published valproic acid (VPA) population pharmacokinetic (PPK) models in adult patients and assessed them using external validation methods to determine predictive performance."	( Published population pharmacokinetic models of valproic acid in adult patients: a systematic review and external validation in a Chinese sample of inpatients with bipolar disorder. de Leon, J; Dong, F; Guo, W; Li, AN; Ruan, CJ; Zang, YN, 2022)	1.26
" Using this fact we aimed to develop an MHD population pharmacokinetic (PPK) model in Chinese adult epileptic patients to facilitate the clinical implementation of model-guided individualised drug therapy."	( Population pharmacokinetics of oxcarbazepine 10-monohydroxy derivative in Chinese adult epileptic patients. Dai, H; Hu, Y; Li, X; Yang, Q; Zhang, X, 2023)	0.91
" A pilot pharmacokinetic (PK) open-labeled parallel study on healthy human volunteers was carried out to assess the PK of FDC of aripiprazole/divalproex sodium in comparison with its individual components with a view to rationalize therapeutic regimen and potentially improve compliance of bipolar patients in future."	( Fixed Dose Combination Tablets of Aripiprazole and Divalproex Sodium: a Pilot Pharmacokinetic Study in Human Volunteers. Ahmed, S; Ahmed, Z; Subhan, F, 2022)	0.72
" Population pharmacokinetic model was developed on NONMEM® software by using first order conditional estimation method for estimation of pharmacokinetic parameters."	( Comparative pharmacokinetics of valproic acid among Pakistani and South Korean patients: A population pharmacokinetic study. Ali, M; Bilal, R; Khan, HM; Khan, RR; Khokhar, MI; Saeed, HA; Shaukat, QU; Usman, M, 2022)	1
" A mixed-effects model was used to analyze the effect of valproic acid on the natural log-transformed pharmacokinetic parameters of vixotrigine and its metabolites including maximum concentration and area under the concentration-time curve from time zero to infinity."	( Evaluation of the Effect of Uridine Diphosphate-Glucuronosyltransferases (UGT) Inhibition by Valproic Acid on Vixotrigine Pharmacokinetics in Healthy Volunteers. Finnigan, H; Kotecha, M; Naik, H; Serenko, M; Zhao, Y, 2022)	1.19
" There are limited studies providing sufficient pharmacokinetic data, thus the variability of concentrations of olanzapine used in Chinese paediatric patients aged 10 to 17 years remains to be evaluated."	( Population pharmacokinetics and dosing optimization of olanzapine in Chinese paediatric patients: Based on the impact of sex and concomitant valproate on clearance. Hu, JQ; Huang, SQ; Kong, W; Li, XL; Liu, SJ; Lu, HQ; Lu, HY; Ni, XJ; Shang, DW; Wen, YG; Xiao, T; Yang, HL; Zhang, M; Zhu, XQ, 2022)	0.72
" A population pharmacokinetic (PopPK) model was established to analyze the PK of DP-VPA and active metabolite VPA."	( Population pharmacokinetics and exposure-safety of lipophilic conjugates prodrug DP-VPA in healthy Chinese subjects for dose regime exploring. Cao, G; Chen, Y; Fan, Y; Guo, B; Hu, J; Li, X; Li, Y; Liu, X; Wang, Y; Wu, H; Wu, J; Wu, X; Xu, X; Yu, J; Yu, P; Zhan, H; Zhang, J, 2023)	0.91

Compound-Compound Interactions

Valproic acid undergoes drug-drug interactions with most of the commonly used anticonvulsants. The aim of this study was to illustrate the mechanism of inhibiting the cell growth in diffuse large B-cell lymphoma.

Excerpt	Reference	Relevance
"Erythrocyte (ENH3) and plasma (PNH3) ammonia levels, liver function tests and plasma valproate concentration were measured in 81 epileptic patients, comprising three therapeutic groups: Group 1 (23 patients) received sodium valproate (VPA) monotherapy, group 2 (33 patients) received sodium valproate combined with phenytoin, carbamazepine, phenobarbitone and/or primidone and group 3 (25 patients) received one or more of these anti-epileptic drugs without sodium valproate."	( Hyperammonaemia and hepatotoxicity during chronic valproate therapy: enhancement by combination with other antiepileptic drugs. Hoffmann, S; Purdie, G; Ratnaike, RN; Rischbieth, RH; Schapel, GJ, 1986)	0.27
"5, and 15 mg/kg), and valproic acid (40, 60, 80, and 120 mg/kg), and those of phenobarbital (10 and 20 mg/kg) in combination with phenytoin (2."	( Effects of phenobarbital in combination with phenytoin or valproic acid on the delayed-matching-to-sample performance of pigeons. Karas, CA; Picker, M; Poling, A, 1986)	0.83
" Purely additive interactions were found for the anticonvulsant effect when valproate was combined with carbamazepine as well as with phenobarbital."	( Anticonvulsant potency and neurotoxicity of valproate alone and in combination with carbamazepine or phenobarbital. Bourgeois, BF, 1988)	0.27
"Antiepileptic drugs interact with a variety of other drugs to affect the pharmacokinetic behavior of either drug."	( Drug interactions between antiepileptic drugs and other drugs. Kutt, H, 1985)	0.27
" Phenytoin in combination with other drugs (anticonvulsives, antibiotics etc."	( [Effects of drug interaction in infancy (author's transl)]. Alterthum, K; Bauer, P; Stünkel, S; Windorfer, A, 1980)	0.26
"Valproic acid undergoes drug-drug interactions with most of the commonly used anticonvulsants."	( Drug interactions with valproic acid. Koch, KM; Levy, RH, 1982)	2.02
" It is often necessary to have lithium combined with other psychopharmacological agents when efforts are aimed at either enhancing a less-than-optimal therapeutic effect or treating other symptoms as well."	( [Drug combinations of lithium: reasons and limitations]. Lagomarsino, AJ, 1993)	0.29
" Because of its widespread and long term use, carbamazepine is frequently prescribed in combination with other drugs, leading to the possibility of drug interactions."	( Clinically significant pharmacokinetic drug interactions with carbamazepine. An update. Perucca, E; Pisani, F; Spina, E, 1996)	0.29
" Patients received phenobarbitone as monotherapy or in combination with either of the antiepileptic drugs carbamazepine or valproic acid."	( Detection of a drug-drug interaction on population-based phenobarbitone clearance using nonlinear mixed-effects modeling. Aoyama, T; Higuchi, S; Ohdo, S; To, H; Yukawa, E, 1998)	0.51
" The mechanism of this proposed interaction may involve drug-drug competition at the level of hepatic glucuronidation (conjugation), although shifts in protein binding cannot be ruled out."	( Increased plasma valproate concentrations when coadministered with guanfacine. Ambrosini, PJ; Sheikh, RM, 1998)	0.3
"The effect of nitrendipine (NTP) alone and in combination with phenytoin (PHT) and valproate (VPA) against maximal electroshock seizures (MES) was studied in rats."	( Anticonvulsant and psychomotor activity of nitrendipine alone and in combination with phenytoin and valproate in rats. Balakrishnan, S; Bhargava, VK; Pandhi, P, )	0.13
"The use of methylphenidate (MPH) in combination with antiepileptic drugs is gaining acceptance for children with epilepsy who have the symptoms of attention-deficit hyperactivity disorder (ADHD)."	( Adverse response to methylphenidate in combination with valproic acid. Gara, L; Roberts, W, 2000)	0.55
" In this study we tested the effect of valproic acid and trichostatin, alone or in combination with hemin, on gamma chain synthesis in human erythroid liquid cultures."	( Valproic acid, trichostatin and their combination with hemin preferentially enhance gamma-globin gene expression in human erythroid liquid cultures. Akel, S; Kollia, P; Loukopoulos, D; Marianna, P; Papassotiriou, Y; Stamoulakatou, A, 2001)	2.02
"Valproic acid, trichostatin and their combination with hemin (all three FDA-approved drugs) preferentially increase gamma-globin chain synthesis and may be helpful for the treatment of hemoglobinopathies."	( Valproic acid, trichostatin and their combination with hemin preferentially enhance gamma-globin gene expression in human erythroid liquid cultures. Akel, S; Kollia, P; Loukopoulos, D; Marianna, P; Papassotiriou, Y; Stamoulakatou, A, 2001)	3.2
" All these effects of VPA were significantly enhanced when combined with INF-alpha which on its own had little or no effect."	( Induction of differentiation and suppression of malignant phenotype of human neuroblastoma BE(2)-C cells by valproic acid: enhancement by combination with interferon-alpha. Blaheta, R; Cinatl, J; Driever, PH; Kotchetkov, R; Vogel, JU, 2002)	0.53
" Treatment with divalproex in combination with an atypical antipsychotic agent resulted in earlier improvements in a range of psychotic symptoms among acutely hospitalized patients with schizophrenia."	( Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia. Casey, DE; Daniel, DG; Sommerville, KW; Tracy, KA; Wassef, AA; Wozniak, P, 2003)	0.32
" Other agents frequently used as mood stabilizers in monotherapy and in combination with lithium are valproate and carbamazepine."	( Drug interactions of lithium and other antimanic/mood-stabilizing medications. Dunner, DL, 2003)	0.32
" Some precautions are warranted in its use, but valproate is generally safe whether administered alone or in combination with other therapies."	( Pharmacokinetics, drug interactions, and tolerability of valproate. DeVane, CL, 2003)	0.32
" They could then enter a 10-week open-label study during which they received risperidone combined with a mood stabilizer."	( Risperidone in combination with mood stabilizers: a 10-week continuation phase study in bipolar I disorder. Bowden, CL; Grossman, F; Myers, JE; Xie, Y, 2004)	0.32
" In this study, we have clarified the mechanism of the drug-drug interaction using PAPM, MEPM, and doripenem [S-4661; (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(3S,5S)-5-[(sulfamoylamino)methyl]-3-pyrrolidinyl]thio]-1-azabicyclo[3."	( Mechanism of the drug interaction between valproic acid and carbapenem antibiotics in monkeys and rats. Inagaki, H; Koike, M; Kominami, G; Mizobuchi, M; Nakajima, Y; Nakamura, M; Takagi, H; Yamaguchi, T, 2004)	0.59
"Quetiapine (QTP) combined with lithium (Li) or divalproex (DVP) for the treatment of mania was evaluated in 2 double-blind, placebo-controlled studies."	( Quetiapine versus placebo in combination with lithium or divalproex for the treatment of bipolar mania. Mullen, J; Paulsson, B; Vågerö, AM; Yatham, LN, 2004)	0.32
"To evaluate the efficacy of olanzapine, in combination with lithium or valproate, for treating depressive symptoms associated with mania."	( Efficacy of olanzapine combined with valproate or lithium in the treatment of dysphoric mania. Akiskal, HS; Baker, RW; Brown, E; Calabrese, JR; Ketter, TA; Schuh, LM; Tohen, M; Trzepacz, PT; Watkin, JG, 2004)	0.32
"Secondary analysis of a 6-week, double-blind, randomised study of olanzapine (5-20 mg/day) or placebo combined with ongoing valproate or lithium open treatment for 344 patients in mixed or manic episodes."	( Efficacy of olanzapine combined with valproate or lithium in the treatment of dysphoric mania. Akiskal, HS; Baker, RW; Brown, E; Calabrese, JR; Ketter, TA; Schuh, LM; Tohen, M; Trzepacz, PT; Watkin, JG, 2004)	0.32
" The aim of this study was to compare the effectiveness and tolerability of topiramate and divalproex in combination with risperidone for treating acute mania patients in a naturalistic treatment setting."	( Topiramate and divalproex in combination with risperidone for acute mania: a randomized open-label study. Bahk, WM; Choi, SK; Chung, SK; Jon, DI; Lee, JS; Pae, CU; Paik, IH; Shin, YC; Woo, JM; Yoon, BH, 2005)	0.33
" In this study, we show for the first time that VPA, in combination with RA and the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (Aza-dC), can overcome the epigenetic barriers to transcription of a prototypical silenced tumor suppressor gene, RARbeta2, in human breast cancer cells."	( Valproic acid, in combination with all-trans retinoic acid and 5-aza-2'-deoxycytidine, restores expression of silenced RARbeta2 in breast cancer cells. Gudas, LJ; Mongan, NP, 2005)	1.77
"Valproate is a well-established anticonvulsant that is increasingly being employed, often in combination with other psychotropics, for its mood-stabilizing properties."	( Psychotropic drug interactions with valproate. Chetty, M; Fleming, J, )	0.13
" Patients received PGB, 600 mg/day (200 mg q8h) for 7 days, in combination with their individualized maintenance monotherapy with valproate (VPA), phenytoin (PHT), lamotrigine (LTG), or carbamazepine (CBZ)."	( Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy. Alvey, CW; Bockbrader, HN; Brodie, MJ; Bron, NJ; Gibson, GL; Hounslow, NJ; Posvar, EL; Randinitis, EJ; Wesche, DL; Wilson, EA, 2005)	0.33
" PGB may be added to VPA, LTG, PHT, or CBZ therapy without concern for pharmacokinetic drug-drug interactions."	( Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy. Alvey, CW; Bockbrader, HN; Brodie, MJ; Bron, NJ; Gibson, GL; Hounslow, NJ; Posvar, EL; Randinitis, EJ; Wesche, DL; Wilson, EA, 2005)	0.33
" For patients with high-risk MDS, VPA may be combined with chemotherapy or demethylating drugs."	( Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia. Fox, F; Gattermann, N; Germing, U; Haas, R; Hildebrandt, B; Knipp, S; Kuendgen, A; Steidl, C; Strupp, C, 2005)	0.62
"To identify symptoms associated with suicidality in bipolar I disorder patients, and to assess suicide risk during treatment with olan-zapine in combination with lithium or divalproex."	( Reduced suicidal ideation in bipolar I disorder mixed-episode patients in a placebo-controlled trial of olanzapine combined with lithium or divalproex. Ahl, J; Baldessarini, RJ; Houston, JP; Kaiser, CJ; Meyers, AL; Tohen, M, 2006)	0.33
"The anticonvulsant and acute adverse (neurotoxic) effects of STP in combination with the various conventional antiepileptic drugs (AEDs), at fixed ratios of 1:3, 1:1, and 3:1, were evaluated in the PTZ and chimney tests in mice using the isobolographic analysis."	( Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis. Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2006)	0.33
"To assess the efficacy of lamotrigine combined with either divalproex or lithium for the treatment of bipolar disorder."	( Lamotrigine combined with divalproex or lithium for bipolar disorder: a case series. Bowden, CL; Jamison, KL; Redmond, JR, 2006)	0.33
"0 or 5 mM), but melatonin (1 or 10 nM) was ineffective alone or in combination with valproic acid, in the first (MCF-7A) subline examined."	( Human melatonin MT1 receptor induction by valproic acid and its effects in combination with melatonin on MCF-7 breast cancer cell proliferation. Brown, GM; Jawed, S; Kim, B; Niles, LP; Ottenhof, T; Werstiuk, ES, 2007)	0.83
" Our results indicate that ABT-510 combined with VPA may be an effective antiangiogenic treatment strategy for children with high-risk neuroblastoma."	( Thrombospondin-1 peptide ABT-510 combined with valproic acid is an effective antiangiogenesis strategy in neuroblastoma. Chlenski, A; Cohn, SL; Henkin, J; Liu, S; Salwen, HR; Tian, Y; Yang, Q; Zeine, R, 2007)	0.6
"The aim of this analysis was to compare the rates of remission/euthymia in patients with bipolar mania receiving quetiapine in combination with lithium/divalproex (QTP+Li/DVP) versus placebo (PBO) in combination with Li/DVP (PBO+Li/DVP)."	( Rates of remission/euthymia with quetiapine in combination with lithium/divalproex for the treatment of acute mania. Mullen, J; Paulsson, B; Sussman, N; Vågerö, M, 2007)	0.34
"At Days 21 and 42, quetiapine combined with Li/DVP compared to Li/DVP monotherapy yielded significant, sustained improvements in the rate of clinical remission/euthymia in patients with bipolar mania."	( Rates of remission/euthymia with quetiapine in combination with lithium/divalproex for the treatment of acute mania. Mullen, J; Paulsson, B; Sussman, N; Vågerö, M, 2007)	0.34
" These results suggest that the plasma cell differentiation factor XBP-1, in combination with activated PKD, can mediate the reactivation of EBV, thereby allowing the viral life cycle to be intimately linked to plasma cell differentiation."	( X-box-binding protein 1 activates lytic Epstein-Barr virus gene expression in combination with protein kinase D. Bhende, PM; Dickerson, SJ; Feng, WH; Kenney, SC; Sun, X, 2007)	0.34
" In the present study, VPA in combination with two differentiating agents, 13-cis retinoic acid and 1,25-dihydroxyvitamin D3, was given to 19 previously untreated patients with MDS or CMML."	( Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes. Hallman, H; Honkanen, T; Juvonen, E; Kauppila, M; Koistinen, P; Kutila, A; Mikkola, M; Nyländen, P; Poikonen, E; Rauhala, A; Savolainen, ER; Siitonen, T; Sinisalo, M; Suominen, M; Terävä, V; Timonen, T, 2007)	1.78
"To determine an optimal biologic dose (OBD) of decitabine as a single agent and then the maximum-tolerated dose (MTD) of valproic acid (VA) combined with decitabine in acute myeloid leukemia (AML)."	( Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. Blum, W; Byrd, JC; Chan, KK; Devine, H; Devine, SM; Grever, MR; Hackanson, B; Heerema, NA; Huynh, L; Kefauver, C; Klisovic, RB; Liu, S; Liu, Z; Lozanski, G; Marcucci, G; Murgo, A; Plass, C; Vukosavljevic, T, 2007)	0.79
"The goal of this study was to determine if manifestations of agitation (ie, physical aggression, physically nonaggressive behavior, and verbally agitated behaviors) show different degrees of response to divalproex sodium (extended release or sprinkles) alone or in combination with second-generation antipsychotic agents."	( Report on an open-label prospective study of divalproex sodium for the behavioral and psychological symptoms of dementia as monotherapy and in combination with second-generation antipsychotic medication. Adkison, L; Ahokpossi, C; Forester, B; Hyde, J; Perez, R; Sribney, W; Vanelli, M, 2007)	0.34
" Daily doses of divalproex (mean dose, 656 mg/d) in combination with a second-generation antipsychotic were 28% lower than divalproex monotherapy (mean dose, 914 mg/d)."	( Report on an open-label prospective study of divalproex sodium for the behavioral and psychological symptoms of dementia as monotherapy and in combination with second-generation antipsychotic medication. Adkison, L; Ahokpossi, C; Forester, B; Hyde, J; Perez, R; Sribney, W; Vanelli, M, 2007)	0.34
"This study examined the efficacy and safety of quetiapine in combination with lithium or divalproex compared with placebo with lithium or divalproex in the prevention of recurrent mood events in bipolar I patients, most recent episode mania, depression, or mixed."	( Efficacy and safety of quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar I disorder (international trial 126). Brecher, M; Eggens, I; Paulsson, B; Persson, I; Suppes, T; Vieta, E, 2008)	0.35
"Treatment with quetiapine in combination with lithium/divalproex significantly increased the time to recurrence of any mood event compared with placebo plus lithium/divalproex."	( Efficacy and safety of quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar I disorder (international trial 126). Brecher, M; Eggens, I; Paulsson, B; Persson, I; Suppes, T; Vieta, E, 2008)	0.35
"Maintenance treatment with quetiapine in combination with lithium/divalproex significantly increased time to recurrence of any event (mania, depression, or mixed) irrespective of the polarity of the index episode compared with placebo with lithium/divalproex."	( Efficacy and safety of quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar I disorder (international trial 126). Brecher, M; Eggens, I; Paulsson, B; Persson, I; Suppes, T; Vieta, E, 2008)	0.35
" When valproic acid is combined with tazarotene or isotretinoin, it does not change their photocarcinogenicity significantly."	( Photocarcinogenesis of topical tazarotene and isotretinoin alone and in combination with valproic acid in hairless mice. Lerche, CM; Philipsen, PA; Sehested, M; Wulf, HC, 2008)	1.05
"To investigate the potential drug-drug interaction (DDI) between lipoic acid (LA) and valproate (VA) via the mitochondrial beta-oxidation pathway in rats."	( Investigation of the drug-drug interaction between alpha-lipoic acid and valproate via mitochondrial beta-oxidation. Browne, ER; Chan, EC; Goh, CW; Neo, AH; New, LS; Phua, LC, 2008)	0.35
"The objective of this study was to evaluate the efficacy and safety of divalproex sodium extended release (divalproex ER) vs placebo in combination with olanzapine or risperidone for the treatment of acute exacerbations of schizophrenia."	( Divalproex ER combined with olanzapine or risperidone for treatment of acute exacerbations of schizophrenia. Abi-Saab, W; Baker, J; Casey, DE; Daniel, DG; Greco, N; Kane, JM; Redden, L; Saltarelli, M; Tamminga, C; Tran-Johnson, T; Wozniak, P, 2009)	0.35
" Treatment was commenced with the HDACi sodium valproate (VPA) in combination with the anti-viral nucleoside analogue ganciclovir (GCV)."	( Sodium valproate in combination with ganciclovir induces lysis of EBV-infected lymphoma cells without impairing EBV-specific T-cell immunity. Corbett, G; Gandhi, MK; Jones, K; Nourse, J, 2010)	0.36
" After at least 12 weeks of clinical stability, 628 patients were randomly assigned to double-blind treatment with quetiapine or placebo, in combination with lithium or divalproex, for up to 104 weeks."	( Maintenance treatment for patients with bipolar I disorder: results from a north american study of quetiapine in combination with lithium or divalproex (trial 127). Brecher, M; Liu, S; Paulsson, B; Suppes, T; Vieta, E, 2009)	0.35
" The goal of this study was to evaluate the anticancer effect of a histone deacetylase inhibitor, valproate, on mesothelioma cells in combination with pemetrexed and cisplatin, the usual first-line regimen of chemotherapy for this tumor."	( Valproate, in combination with pemetrexed and cisplatin, provides additional efficacy to the treatment of malignant mesothelioma. Burny, A; Delvenne, P; Grigoriu, B; Hubert, P; Mascaux, C; Scherpereel, A; Vandermeers, F; Willems, L, 2009)	0.35
" As expected, valproate alone or combined with pemetrexed and cisplatin triggers hyperacetylation of histone H3."	( Valproate, in combination with pemetrexed and cisplatin, provides additional efficacy to the treatment of malignant mesothelioma. Burny, A; Delvenne, P; Grigoriu, B; Hubert, P; Mascaux, C; Scherpereel, A; Vandermeers, F; Willems, L, 2009)	0.35
"These observations support the potential additional efficacy of valproate in combination with pemetrexed and cisplatin for treatment of malignant mesothelioma."	( Valproate, in combination with pemetrexed and cisplatin, provides additional efficacy to the treatment of malignant mesothelioma. Burny, A; Delvenne, P; Grigoriu, B; Hubert, P; Mascaux, C; Scherpereel, A; Vandermeers, F; Willems, L, 2009)	0.35
"The present study investigated the mechanism underlying the antitumor activity of the histone deacetylases inhibitor valproic acid (VPA), alone and in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative (HS-1200), or the proteasome inhibitor lactacystin on cultured anaplastic thyroid carcinoma KAT-18 cells."	( Efficacy on anaplastic thyroid carcinoma of valproic acid alone or in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative, or lactacystin. Kang, DY; Kim, SH; Kim, TH; Park, KJ; Park, MK; Suh, H; Yoo, YH, 2009)	0.82
" Adverse-effect profiles of the drugs in combination were determined and brain AED concentrations were measured."	( Isobolographic characterization of the anticonvulsant interaction profiles of levetiracetam in combination with clonazepam, ethosuximide, phenobarbital and valproate in the mouse pentylenetetrazole-induced seizure model. Andres-Mach, MM; Czuczwar, SJ; Dudra-Jastrzebska, M; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2009)	0.35
" The abovementioned activity of VPA as a differentiation agent suggested that it might be worth investigating its possible therapeutic potential in synergistic combination with FTS."	( Downregulation of survivin and aurora A by histone deacetylase and RAS inhibitors: a new drug combination for cancer therapy. Biran, A; Brownstein, M; Haklai, R; Kloog, Y, 2011)	0.37
" This case highlights the interplay between pharmacogenetic factors, drug-drug interactions, and dose-related toxicity in a child."	( Fatal hydrocodone overdose in a child: pharmacogenetics and drug interactions. Carleton, BC; Ciszkowski, C; Gong, IY; Hayden, MR; Hildebrandt, D; Koren, G; Lauwers, AE; Madadi, P; Ross, CJ; Schwarz, UI; Sistonen, J, 2010)	0.36
"Clinicians prescribing divalproex sodium (DVX) are well aware of its potential to cause a drug-drug interaction."	( Drug interaction between carbapenems and extended-release divalproex sodium in a patient with schizoaffective disorder. Candeloro, CL; Christopher, EJ; Muzyk, AJ, )	0.13
"Our case report is the first to document this drug-drug interaction in a patient diagnosed with schizoaffective disorder, bipolar type."	( Drug interaction between carbapenems and extended-release divalproex sodium in a patient with schizoaffective disorder. Candeloro, CL; Christopher, EJ; Muzyk, AJ, )	0.13
" We determined the anticancer effects of VPA combined with 5-FU in these cell lines."	( Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell lines. Hanaoka, J; Ikemoto, T; Imura, S; Ishibashi, H; Iwahashi, S; Mori, H; Morine, Y; Ochir, TL; Shimada, M; Utsunomiya, T, 2011)	0.37
"To evaluate the efficacy and adverse effect of valproic acid (VPA) in combination with low dose chemotherapy on intermediate and high-risk myelodysplastic syndrome."	( [The efficacy and safety of valproic acid in combination with low dose chemotherapy on intermediate and high-risk myelodysplastic syndrome]. Ge, GM; Han, XL; He, LS; Huang, Y; Wu, S; Yan, YP; Zhang, QY, 2011)	0.92
"With acceptable adverse effect, the low dose chemotherapy in combination with VPA regimen is effective for the treatment of intermediate and high-risk myelodysplastic syndrome."	( [The efficacy and safety of valproic acid in combination with low dose chemotherapy on intermediate and high-risk myelodysplastic syndrome]. Ge, GM; Han, XL; He, LS; Huang, Y; Wu, S; Yan, YP; Zhang, QY, 2011)	0.66
" Since strong anti-tumor properties became evident with respect to cell growth and adhesion dynamics, the triple drug combination might provide progress in the treatment of advanced prostate cancer."	( Molecular targeting of prostate cancer cells by a triple drug combination down-regulates integrin driven adhesion processes, delays cell cycle progression and interferes with the cdk-cyclin axis. Blaheta, RA; Haferkamp, A; Hudak, L; Juengel, E; Makarević, J; Seibel, JM; Tsaur, I; Waaga-Gasser, A; Wedel, S, 2011)	0.37
" To demonstrate a case of a 15 year old girl suffering from refractory epilepsy with underlying focal cortical dysplasia (FCD), whose seizure deterioration was most probably associated with drug-drug interactions between prescribed common antiepileptic drugs, namely valproic acid, phenobarbital or the prodrug primidon and carbamazepine."	( Antiepleptic drug interactions: a clinical case demonstration. Klapková, E; Komárek, V; Tesfaye, H; Tesfayeová, A, 2011)	0.55
" The authors examined the in vitro and clinical activity of the histone deacetylase inhibitor valproic acid (VA) combined with cytosine arabinoside (AraC) in elderly patients with AML unsuited to intensive therapy."	( Valproic acid combined with cytosine arabinoside in elderly patients with acute myeloid leukemia has in vitro but limited clinical activity. Fan, HM; Gill, D; Keane, C; Lane, S; McMillan, NA; Mollee, P; Murphy, R; Saunders, N; Spurr, T, 2012)	2.04
" In conclusion, we identified HSPA1A as a possible therapeutic target, in combination with HDACi, for lymphoid neoplasms."	( Proteomic study identified HSP 70 kDa protein 1A as a possible therapeutic target, in combination with histone deacetylase inhibitors, for lymphoid neoplasms. Fujii, K; Hamada, T; Ikeda, K; Iwatsuki, K; Kondo, T; Suzuki, N; Yamamoto, T, 2012)	0.38
"To investigate potential drug-drug interactions between clobazam and cytochrome P450 (CYP) isoenzyme substrates, inhibitors, and inducers."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
"Two, prospective, open-label, single-center, drug-drug interaction (DDI) studies and a population pharmacokinetics analysis of seven multicenter phase II-III trials."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
"Fifty-four healthy adult volunteers were enrolled in the two drug-drug interaction studies; 53 completed the studies."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
"In the first drug-drug interaction study, 36 participants received a single oral dose of clobazam 10 mg on day 1, followed by either ketoconazole 400 mg once/day or omeprazole 40 mg once/day on days 17-22, with a single dose of clobazam 10 mg coadministered on day 22, to study the effects of CYP3A4 or CYP2C19 inhibition, respectively, on clobazam and its active metabolite N-desmethylclobazam (N-CLB)."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
" In the second DDI study, no clinically significant drug-drug interactions were observed between clobazam 40 mg and the CYP probe substrates caffeine or tolbutamide."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
"These findings suggest no clinically meaningful drug-drug interactions between clobazam and drugs metabolized by CYP3A4, CYP2C19, CYP1A2, or CYP2C9."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
"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
" This study summarizes 6 cases of drug-drug interactions between VPA and carbapenem antibiotics."	( Reduced valproic acid serum concentrations due to drug interactions with carbapenem antibiotics: overview of 6 cases. Cho, JY; Han, HK; Jang, IJ; Kim, TE; Lim, KS; Park, MK; Shin, KH; Shin, SG; Yi, SJ; Yu, KS, 2012)	0.81
"In order to investigate the mechanisms and therapeutic effects of valproate combined with lithium carbonate on mouse model of Parkinson's disease (PD), male C57BL/6 mice were injected into intraperitoneal with valproate (20 μg/ml) combined with lithium carbonate (10 μg/ml) for 7 days following 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) (30 mg/kg) administration, and the effects on motor function were analyzed."	( Therapeutic effects of valproate combined with lithium carbonate on MPTP-induced parkinsonism in mice: possible mediation through enhanced autophagy. Bai, LM; Chen, XP; Li, XZ; Zhang, H; Zhao, K; Zhou, XP, 2013)	0.39
" Patients were treated with escalating doses of decitabine (5-15 mg/m(2)) IV for 10 days in combination with VPA (10-20 mg/kg/day) PO on days 5-21 of a 28-day cycle."	( Phase I study of 5-aza-2'-deoxycytidine in combination with valproic acid in non-small-cell lung cancer. Aimiuwu, J; Chan, KK; Chu, BF; Grever, MR; Karpenko, MJ; Liu, Z; Otterson, GA; Villalona-Calero, MA, 2013)	0.63
"To determine the efficacy and safety of quetiapine combined with lithium or divalproex for preventing mood events in patients with bipolar I disorder."	( Maintenance treatment with quetiapine when combined with either lithium or divalproex in bipolar I disorder: analysis of two large randomized, placebo-controlled trials. Ekholm, B; Gustafsson, U; Suppes, T; Vieta, E, 2013)	0.39
"In patients with bipolar I disorder previously stabilized on quetiapine and lithium or divalproex, maintenance therapy with quetiapine significantly increased the time to recurrence of a mood event (mania or depression) versus placebo, regardless of whether it was combined with lithium or divalproex."	( Maintenance treatment with quetiapine when combined with either lithium or divalproex in bipolar I disorder: analysis of two large randomized, placebo-controlled trials. Ekholm, B; Gustafsson, U; Suppes, T; Vieta, E, 2013)	0.39
" Therefore, we studied the effect of polo-like kinase 1 (Plk1) inhibitors on prostate cancer cells as a single agent and in combination with histone deacetylase (HDAC) inhibitors valproic acid and vorinostat."	( Targeting prostate cancer cell lines with polo-like kinase 1 inhibitors as a single agent and in combination with histone deacetylase inhibitors. Carducci, MA; Gonzalez, M; Hammers, H; Kachhap, SK; Kaelber, NS; Kim, E; Kortenhorst, MS; Mendonca, J; van Diest, PJ; Wissing, MD, 2013)	0.58
" Sequential treatment with azacitidine and valproic acid (VPA) in combination with carboplatin may overcome resistance to platinum-based therapy, and we conducted a phase I trial to assess safety, maximum tolerated dose (MTD), and clinical correlates."	( Methylation and histone deacetylase inhibition in combination with platinum treatment in patients with advanced malignancies. Bustinza-Linares, E; Falchook, GS; Fu, S; Hong, DS; Hu, W; Kurzrock, R; Moulder, S; Naing, A; Parkhurst, KL; Sood, AK; Wheler, JJ, 2013)	0.65
" For patients who used CBZ in combination with an enzyme-inducing antiepileptic drug (AED: PHT or PB), individuals carrying the CYP3A5*1 allele (CYP3A5 expressers) showed a trend of having higher CBZ clearance and lower dose-adjusted CBZ level as compared to individuals carrying the CYP3A5*3 allele, even though no statistical significance was recorded."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.59
"When CBZ was used in combination with enzyme-inducing AED, CYP3A5 expressers yielded a trend toward greater susceptibility to change in CBZ clearance and showed lower dose-adjusted CBZ levels compared to CYP3A5 non-expressers."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.59
" In the present work, we tried to increase the adenovirus transduction level and mediated gene delivery of human adipose stem cells with the use of valproic acid (VPA) and determined the proper concentration and duration of treatment alone or in combination with ViraDuctin adenovirus transduction reagent."	( Evaluation of optimal concentration and exposure duration of valproic acid alone or in combination with ViraDuctin to augment adenovirus transduction in human adipose stem cells. Azadmanesh, K; Hartoonian, C; Khorramizadeh, MR; Modarresi, MH; Negahdari, B; Shokrghozar, MA; Shokrgozar, MA, 2014)	0.84
" The effects of various doses and exposure periods of VPA on CAR expression in human adipose stem cells were speculated by quantitative real-time polymerase chain reaction and adenoviral transduction rate by flow cytometry in different doses and time intervals of VPA and in combination with ViraDuctin transduction reagent."	( Evaluation of optimal concentration and exposure duration of valproic acid alone or in combination with ViraDuctin to augment adenovirus transduction in human adipose stem cells. Azadmanesh, K; Hartoonian, C; Khorramizadeh, MR; Modarresi, MH; Negahdari, B; Shokrghozar, MA; Shokrgozar, MA, 2014)	0.64
"These results confirm that addition of VPA to hASCs alone or in combination with ViraDuctin has enhancing effects on adenoviral transduction rate, which can be auspicious in adenoviral-mediated gene therapy."	( Evaluation of optimal concentration and exposure duration of valproic acid alone or in combination with ViraDuctin to augment adenovirus transduction in human adipose stem cells. Azadmanesh, K; Hartoonian, C; Khorramizadeh, MR; Modarresi, MH; Negahdari, B; Shokrghozar, MA; Shokrgozar, MA, 2014)	0.64
"The aim of this study was to illustrate the mechanism of inhibiting the cell growth in diffuse large B-cell lymphoma by histone deacetylase inhibitor valproic acid (VPA) combined with mTOR inhibitor temsirolimus (TEM)."	( [Mechanism of inhibiting the cell growth in diffuse large B-cell lymphoma by valproic acid combined with temsirolimus]. Cheng, S; Dong, LH; Wang, L; Zhao, WL; Zhao, Y; Zheng, Z, 2013)	0.82
" Together our findings indicate that valproate which act as inhibitor of cell proliferation and inducer of apoptosis in human cancer MIAPaca2 cells when used in combination with nicotinamide makes it a potentially good candidate for new anticancer drug development."	( Synergistic anticancer activity of valproate combined with nicotinamide enhances anti-proliferation response and apoptosis in MIAPaca2 cells. Ahmadian, S; Jafary, H; Soleimani, M, 2014)	0.4
" The effects of VPA in combination with PIs on the growth of colorectal cancer cells were assessed with regard to proliferation, cell cycle, apoptosis, reactive oxygen species (ROS) generation and the expression of genes that control the cell cycle, apoptosis and pro-survival/stress-related pathways."	( Valproic acid, an anti-epileptic drug and a histone deacetylase inhibitor, in combination with proteasome inhibitors exerts antiproliferative, pro-apoptotic and chemosensitizing effects in human colorectal cancer cells: underlying molecular mechanisms. Abaza, MS; Al-Attiyah, RJ; Bahman, AM, 2014)	1.85
"This study was aimed to investigate the apoptosis-inducing effect of valproic acid (VPA) combined with arsenic trioxide (ATO) on human multiple myeloma RPMI 8226 cells and its mechanism."	( [Apoptosis-inducing effect of valproic acid combined with arsenic trioxide on RPMI 8226 cells and its mechanism]. Wang, XN; Zhang, M, 2014)	0.93
" Hydralazine-valproate is safe when used alone or in combination with chemotherapy or chemoradiation."	( Hydralazine-valproate: a repositioned drug combination for the epigenetic therapy of cancer. Cetina, L; Chavez-Blanco, A; Coronel, J; Dueñas-Gonzalez, A; González-Fierro, A; Taja-Chayeb, L, 2014)	0.4
" Primary GBM cells were treated with VPA as a monotherapy and in combination with temozolomide and irradiation."	( The effect of valproic acid in combination with irradiation and temozolomide on primary human glioblastoma cells. Cosgrove, L; Day, B; Fay, M; Head, R; Hosein, AN; Lim, YC; Martin, JH; Rose, S; Sminia, P; Stringer, B, 2015)	0.78
" Patients are randomized to one of the four treatment groups: DAC alone or in combination with VPA or ATRA or with both add-on drugs."	( DECIDER: prospective randomized multicenter phase II trial of low-dose decitabine (DAC) administered alone or in combination with the histone deacetylase inhibitor valproic acid (VPA) and all-trans retinoic acid (ATRA) in patients >60 years with acute mye Cieslik, C; Döhner, K; Grishina, O; Hackanson, B; Lübbert, M; Lubrich, B; May, AM; Müller, MJ; Schmoor, C, 2015)	0.61
" This study was designed to investigate the effect of VPA combined with therapeutic hypothermia (HT) in an asphyxial cardiac arrest rat model."	( Effect of valproic acid combined with therapeutic hypothermia on neurologic outcome in asphyxial cardiac arrest model of rats. Hwang, JE; Jo, YH; Kim, K; Kim, MA; Lee, JH; Lee, MJ, 2015)	0.82
" We conclude that targeting MC2 Ag, combined with epigenetic drug-enhanced antigenicity, allows for significant and tumor-selective T cell responses."	( MAGE-C2-Specific TCRs Combined with Epigenetic Drug-Enhanced Antigenicity Yield Robust and Tumor-Selective T Cell Responses. Coulie, PG; da Silva, M; Debets, R; Kunert, A; Lamers, C; Sleijfer, S; van Brakel, M; van Steenbergen-Langeveld, S, 2016)	0.43
"The combination of anticonvulsant mood stabilizers with antipsychotic drugs may lead to clinically relevant drug-drug interactions."	( Pharmacokinetic Drug-Drug Interactions of Mood Stabilizers and Risperidone in Patients Under Combined Treatment. Gründer, G; Haen, E; Hiemke, C; Lammertz, SE; Paulzen, M; Schoretsanitis, G; Schruers, KR; Stegmann, B, 2016)	0.43
" In another independent set of experiments, similar results of drug combination responses were also found."	( Anti-Epileptic Drug Combination Efficacy in an In Vitro Seizure Model - Phenytoin and Valproate, Lamotrigine and Valproate. French, CR; O'Brien, TJ; Taing, KD; Williams, DA, 2017)	0.46
" A retrospective analysis of VPA therapeutic drug monitoring (TDM) records was performed to investigate this VPA pharmacokinetics drug-drug interaction."	( Drug-drug interaction between valproic acid and meropenem: a retrospective analysis of electronic medical records from neurosurgery inpatients. Chen, XP; Chen, Y; Du, C; Fan, SS; Peng, ZF; Wen, ZP; Xiao, J; Xie, YY; Yin, T; Zhang, W; Zhou, BT, 2017)	0.74
" The aim of the study was to conduct an in vivo evaluation of the relationship between treatments with synthetic cannabinoid arachidonyl-2'-chloroethylamide (ACEA) alone or in combination with valproic acid (VPA) and hippocampal neurogenesis in a mouse pilocarpine model of epilepsy."	( A Long-Term Treatment with Arachidonyl-2'-Chloroethylamide Combined with Valproate Increases Neurogenesis in a Mouse Pilocarpine Model of Epilepsy. Andres-Mach, M; Dudra-Jastrzębska, M; Haratym, J; Haratym-Maj, A; Maj, M; Rola, R; Zagaja, M; Łuszczki, JJ, 2017)	0.64
"Human in vitro and dog in vitro/in vivo researches indicate that the drug-drug interaction (DDI) of decreased plasma valproic acid (VPA) concentration by co-administration of carbapenem antibiotics is caused by inhibition of acylpeptide hydrolase (APEH)-mediated VPA acylglucuronide (VPA-G) hydrolysis by carbapenems."	( Observation of Clinically Relevant Drug Interaction in Chimeric Mice with Humanized Livers: The Case of Valproic Acid and Carbapenem Antibiotics. Chiba, K; Goda, R; Koyama, K; Kuga, H; Nakai, D; Suzuki, E, 2017)	0.88
" To evaluate the recurrence prevention efficacy of lurasidone for the maintenance treatment of bipolar I disorder, patients received up to 20 weeks of open-label lurasidone (20-80mg/d) combined with lithium or valproate during an initial stabilization phase."	( Lurasidone in combination with lithium or valproate for the maintenance treatment of bipolar I disorder. Calabrese, JR; Cucchiaro, J; Loebel, A; Mao, Y; Pikalov, A; Streicher, C, 2017)	0.46
"High-dose valproic acid in combination with hypothermic-targeted temperature management has been reported to synergistically improve neurologic outcomes after cardiac arrest."	( Valproic Acid Combined With Postcardiac Arrest Hypothermic-Targeted Temperature Management Prevents Delayed Seizures and Improves Survival in a Rat Cardiac Arrest Model. Neumar, RW; Oh, JS; Stacey, WC; Tulasi, J; Xiaodan, R, 2017)	2.3
"High-dose valproic acid combined with hypothermic-targeted temperature management prevents postcardiac arrest seizures and improves survival."	( Valproic Acid Combined With Postcardiac Arrest Hypothermic-Targeted Temperature Management Prevents Delayed Seizures and Improves Survival in a Rat Cardiac Arrest Model. Neumar, RW; Oh, JS; Stacey, WC; Tulasi, J; Xiaodan, R, 2017)	2.3
" Our study objective was to design and validate a mechanistic model of VPA disposition in adults and children; and evaluate its predictive performance of drug-drug interactions (DDIs)."	( Physiologically based pharmacokinetic modeling of disposition and drug-drug interactions for valproic acid and divalproex. Alam, HB; Conner, TM; Georgoff, PE; Nikolian, VC; Pai, MP; Reed, RC; Sun, D; Zhang, T, 2018)	0.7
" Here, we demonstrated that VPA combined with ZOL revealed the synergistic effect in enhancing antitumor efficacy of γδ T cells against osteosarcoma cells."	( Valproic Acid Combined with Zoledronate Enhance γδ T Cell-Mediated Cytotoxicity against Osteosarcoma Cells Li, B; Li, H; Lin, N; Lin, P; Sun, L; Teng, W; Wang, S; Wang, Z; Xue, D; Ye, C; Ye, Z; Zhang, W; Zhou, X, 2018)	1.92
"The current study evaluates the anticonvulsant effect of valproic acid (VPA) alone or combined with low dose γ-irradiation (LDR) against pentylenetetrazol-induced convulsions in rats."	( Effect of valproic acid alone or combined with low dose gamma irradiation in modulating PTZ-induced convulsions in rats involving AKT/m-TOR pathway. Kenawy, SA; Lotfy, DM; Mohamed, SH; Safar, MM, 2018)	1.13
" VPA alone or combined with LDR ameliorated, the convulsions and caused significant improvement in behavioural changes and other tested parameters compared to normal control."	( Effect of valproic acid alone or combined with low dose gamma irradiation in modulating PTZ-induced convulsions in rats involving AKT/m-TOR pathway. Kenawy, SA; Lotfy, DM; Mohamed, SH; Safar, MM, 2018)	0.88
"Phase I, open-label, randomized, single-dose, 3-period crossover study assessing pharmacokinetics (PK) and safety of ZX008, a liquid oral formulation of fenfluramine (FFA) under development for adjunctive treatment of Dravet syndrome and Lennox-Gastaut syndrome, administered with and without a combined antiepileptic drug (AED) regimen of stiripentol (STP), valproate (VPA), and clobazam (CLB) (STP regimen)."	( A phase I, randomized, open-label, single-dose, 3-period crossover study to evaluate the drug-drug interaction between ZX008 (fenfluramine HCl oral solution) and a regimen of stiripentol, clobazam, and valproate in healthy subjects . Boyd, B; Farfel, GM; Galer, BS; Gammaitoni, A; Smith, S, 2019)	0.51
" Additionally, we established the relationship between treatment with ACEA in combination with LEV and hippocampal neurogenesis in mouse brain."	( Levetiracetam combined with ACEA, highly selective cannabinoid CB1 receptor agonist changes neurogenesis in mouse brain. Andres-Mach, M; Haratym-Maj, A; Maj, M; Rola, R; Szewczyk, A; Zagaja, M; Łuszczki, JJ, 2019)	0.51
"This study aimed to assess the molecular mechanism of the histone deacetylase inhibitor (HDACI) valproate acid (VPA) alone or in combination with the antipsychotic drug chlorpromazine in the epigenetic regulation of schizophrenia."	( Molecular mechanism of action of valproate acid alone or in combination with chlorpromazine in the epigenetic regulation of schizophrenia. Geng, YM; Li, HY; Su, JP; Xue, JT, )	0.13
" The effect of losartan and enalapril alone and in combination with sodium valproate on seizures, cognition, cardiac histopathology, and serum brain-derived neurotropic factor (BDNF) levels were determined."	( Effects of enalapril and losartan alone and in combination with sodium valproate on seizures, memory, and cardiac changes in rats. Arava, S; Gupta, YK; Joshi, D; Katyal, J, 2019)	0.51
" Sodium valproate alone or in combination with losartan or enalapril prevented kindled seizures."	( Effects of enalapril and losartan alone and in combination with sodium valproate on seizures, memory, and cardiac changes in rats. Arava, S; Gupta, YK; Joshi, D; Katyal, J, 2019)	0.51
" This open-label, fixed-sequence, drug-drug interaction, healthy volunteer trial investigated the impact of cannabidiol on steady-state pharmacokinetics of clobazam (and N-desmethylclobazam), stiripentol, and valproate; the reciprocal effect of clobazam, stiripentol, and valproate on cannabidiol and its major metabolites (7-hydroxy-cannabidiol [7-OH-CBD] and 7-carboxy-cannabidiol [7-COOH-CBD]); and cannabidiol safety and tolerability when coadministered with each antiepileptic drug."	( A Phase 1, Open-Label, Pharmacokinetic Trial to Investigate Possible Drug-Drug Interactions Between Clobazam, Stiripentol, or Valproate and Cannabidiol in Healthy Subjects. Blakey, G; Crockett, J; Morrison, G; Sommerville, K, 2019)	0.51
" The apoptotic effects of GE in combination with VPA were more significant that of each\ compound alone."	( Effect of DNA Methyltransferase in Comparison to and\ in Combination with Histone Deacetylase Inhibitors on\ Hepatocellular Carcinoma HepG2 Cell Line Kavoosi, F; Sanaei, M, 2019)	0.51
"Atypical antipsychotics are used for the treatment of acute mania, either as monotherapy or in combination with lithium or divalproex, which have a better tolerability profile as compared with typical antipsychotics."	( Efficacy and Safety of Asenapine Versus Olanzapine in Combination With Divalproex for Acute Mania: A Randomized Controlled Trial. Arora, M; Gillani, Z; Mahajan, V; Praharaj, SK; Tandon, VR, )	0.13
"One hundred twenty patients aged 18 to 55 years, diagnosed with manic episode, were randomized to receive either flexible dose of sublingual asenapine (10-20 mg/d) or tablet olanzapine (10-20 mg/d), in combination with valproate 20 mg/kg per day for a period of 6 weeks."	( Efficacy and Safety of Asenapine Versus Olanzapine in Combination With Divalproex for Acute Mania: A Randomized Controlled Trial. Arora, M; Gillani, Z; Mahajan, V; Praharaj, SK; Tandon, VR, )	0.13
"This study found that asenapine was an effective and well-tolerated atypical antipsychotic alternative to olanzapine in combination with divalproex for the short-term management of acute mania."	( Efficacy and Safety of Asenapine Versus Olanzapine in Combination With Divalproex for Acute Mania: A Randomized Controlled Trial. Arora, M; Gillani, Z; Mahajan, V; Praharaj, SK; Tandon, VR, )	0.13
" In the case of a treatment of valproate combined with dipyrone, a close monitoring of the valproate level is recommended."	( [Medicinal Complex Therapy - Drug Interaction of Valproate and Dipyrone]. Green, K; Kliem, A; Mattern, M, 2020)	0.56
" In conclusion, MDC-1112 should be further explored as a potential agent to be used in combination with GEM for treating PC."	( Phospho-valproic acid (MDC-1112) reduces pancreatic cancer growth in patient-derived tumor xenografts and KPC mice: enhanced efficacy when combined with gemcitabine. Digiovanni, MG; Lacomb, JF; Luo, D; Mackenzie, GG; Rigas, B; Wei, R; Williams, JL, 2020)	0.99
"DNA-hypomethylating agents are studied in combination with other epigenetic drugs, such as histone deacetylase inhibitors or differentiation inducers (eg, retinoids), in myeloid neoplasias."	( Valproate and Retinoic Acid in Combination With Decitabine in Elderly Nonfit Patients With Acute Myeloid Leukemia: Results of a Multicenter, Randomized, 2 × 2, Phase II Trial. Becker, H; Brugger, W; Bug, G; Crysandt, M; De Wit, M; Döhner, H; Döhner, K; Duyster, J; Ganser, A; Germing, U; Giagounidis, A; Götze, KS; Grishina, O; Hackanson, B; Heil, G; Heuser, M; Jost, E; Krauter, J; Kuendgen, A; Lindemann, HW; Lübbert, M; May, AM; Müller-Tidow, C; Neubauer, A; Salih, HR; Schittenhelm, MM; Schlenk, RF; Schmoor, C; Scholl, S; Schwaenen, C; Thol, F; Wäsch, R, 2020)	0.56
"We sought to explore the effects of sodium valproate combined with lamotrigine on quality of life and serum inflammatory factors in patients with poststroke secondary epilepsy."	( Effects of Sodium Valproate Combined with Lamotrigine on Quality of Life and Serum Inflammatory Factors in Patients with Poststroke Secondary Epilepsy. Guo, D; Hao, F; Li, X; Liu, X; Sun, J; Tang, W; Tao, S, 2020)	0.56
"A total of 145 patients with post-stroke secondary epilepsy admitted to our hospital from January 2017 to June 2018 were collected: 76 treated with sodium valproate combined with lamotrigine (study group) and 69 patients treated with sodium valproate alone (control group)."	( Effects of Sodium Valproate Combined with Lamotrigine on Quality of Life and Serum Inflammatory Factors in Patients with Poststroke Secondary Epilepsy. Guo, D; Hao, F; Li, X; Liu, X; Sun, J; Tang, W; Tao, S, 2020)	0.56
"Sodium valproate combined with lamotrigine has better clinical efficacy and higher safety in the treatment of poststroke secondary epilepsy and is able to reduce the expression levels of serum inflammatory factors."	( Effects of Sodium Valproate Combined with Lamotrigine on Quality of Life and Serum Inflammatory Factors in Patients with Poststroke Secondary Epilepsy. Guo, D; Hao, F; Li, X; Liu, X; Sun, J; Tang, W; Tao, S, 2020)	0.56
" It is important to consider the possibility of drug-drug interactions (DDIs)."	( Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs. Critchley, D; Gidal, B; Morrison, G; Patsalos, PN; Szaflarski, JP; VanLandingham, K, 2020)	0.56
"The dolutegravir/valproic acid drug-drug interaction (DDI) is suggested to be caused by protein displacement."	( The dolutegravir/valproic acid drug-drug interaction is primarily based on protein displacement. Bax, H; Bollen, PDJ; Burger, DM; Colbers, A; de Mendonca Melo, M; de Vries-Sluijs, TEMS; Nouwen, J; Prins, HAB; Rijnders, BJA; Rokx, C; van Nood, E; Velthoven-Graafland, K; Verbon, A, 2021)	1.3
" The aim of this study was to compare the differential effects of standard chemotherapy regimens (FEC: 5-fluorouracil plus epirubicine plus cyclophosphamide) in combination with epigenetic modulators (decitabine, valproic acid): (a) on gene methylation levels of selected tumour biomarkers (LINE-1, uPA, PAI-1, DAPK); (b) their expression status (uPA and PAI-1); (c) differentiation status (5meC and H3K27me3)."	( Epigenetic modulators combination with chemotherapy in breast cancer cells. Akgun, O; Ari, F; Magdolen, V; Napieralski, R; Ulukaya, E, 2021)	0.81
" Carbamazepine combined with valproic acid significantly increased epoxide levels in milk and maternal serum but not in breastfed infants."	( Therapeutic monitoring of carbamazepine and its active metabolite during the 1st postnatal month: Influence of drug interactions. Brozmanova, H; Grundmann, M; Kacirova, I, 2021)	0.91
" Pharmacokinetic drug-drug interactions (DDIs) between antiseizure medications (ASMs) and anti-infectives can occur and influence their efficacy or cause toxicity."	( A review of pharmacokinetic drug interactions between antimicrobial and antiseizure medications in children. Lattanzi, S; Zaccara, G, 2021)	0.62
"Quetiapine combined with sodium valproate is an effective and more suitable drug treatment for Alzheimer's disease."	( Quetiapine Combined with Sodium Valproate in Patients with Alzheimer's Disease with Mental and Behavioral Symptoms Efficacy Observation. Fu, K; He, X; Liu, W; Xu, J; Xu, P; Zhang, Z, 2022)	0.72
"While the beneficial effects of medications are numerous, drug-drug interactions may lead to adverse drug reactions that are preventable causes of morbidity and mortality."	( Drug interactions in hospital prescriptions in Denmark: Prevalence and associations with adverse outcomes. Andersen, SE; Belling, KG; Biel, JH; Brunak, S; Eriksson, R; Kaas-Hansen, BS; Leal Rodríguez, C, 2022)	0.72
" We measured the prevalence of potential drug-drug interactions in general and discouraged drug pairs in particular during admissions and associations with adverse outcomes: post-discharge all-cause mortality rate, readmission rate and length-of-stay."	( Drug interactions in hospital prescriptions in Denmark: Prevalence and associations with adverse outcomes. Andersen, SE; Belling, KG; Biel, JH; Brunak, S; Eriksson, R; Kaas-Hansen, BS; Leal Rodríguez, C, 2022)	0.72
"Among 2 886 227 hospital admissions (945 475 patients; median age 62 years [IQR: 41-74]; 54% female; median number of drugs 7 [IQR: 4-11]), patients in 1 836 170 admissions were exposed to at least one potential drug-drug interaction (659 525 patients; median age 65 years [IQR: 49-77]; 54% female; median number of drugs 9 [IQR: 6-13]) and in 27 605 admissions to a discouraged drug pair (18 192 patients; median age 68 years [IQR: 58-77]; female 46%; median number of drugs 16 [IQR: 11-22])."	( Drug interactions in hospital prescriptions in Denmark: Prevalence and associations with adverse outcomes. Andersen, SE; Belling, KG; Biel, JH; Brunak, S; Eriksson, R; Kaas-Hansen, BS; Leal Rodríguez, C, 2022)	0.72
"Well-described potential drug-drug interactions are still missed and alerts at point of prescription may reduce the risk of harming patients; prescribing clinicians should be alert when using strong inhibitor/inducer drugs (i."	( Drug interactions in hospital prescriptions in Denmark: Prevalence and associations with adverse outcomes. Andersen, SE; Belling, KG; Biel, JH; Brunak, S; Eriksson, R; Kaas-Hansen, BS; Leal Rodríguez, C, 2022)	0.72
" The aim of the present study was to assess and evaluate the potential drug-drug interaction (DDI) between Bu and VPA."	( Impact of valproic acid on busulfan pharmacokinetics: In vitro assessment of potential drug-drug interaction. Al-Enezi, BF; Al-Hasawi, N; Matar, KM, 2023)	1.31
"To investigate the efficacy and mechanisms of Dingxian pill combined with valproic acid (VPA) on pentylenetetrazol-induced chronical epilepsy in rats."	( Efficacy and mechanisms of Dingxian pill combined with valproic acid on pentylenetetrazol-induced chronic epilepsy in rats. Dongxiao, QU; Guoyi, LI; Jie, T; Jiwei, C; Liji, C; Limin, Z; Qian, X; Yiqin, GE; Yonghua, X; Yudan, Z, 2023)	1.39

Bioavailability

The study examined relative bioavailability of a novel valproic acid (VPA) delayed-release (DR) soft gelatin capsule formulation to divalproex sodium DR tablet under fasting conditions.

Excerpt	Reference	Relevance
" They appear to be well absorbed when given by mouth, but their patterns of distribution within the body are different."	( Pharmacokinetics of drugs used for petit mal 'absence' epilepsy. Eadie, MJ; McKauge, L; Smith, GA; Tyrer, JH, 1977)	0.26
" In two patients, the route of administration was changed from rectal to an equivalent oral dose with continuing control of seizures and minimal change in plasma levels, suggesting that bioavailability is similar for the two forms of the drug."	( Rectal administration of sodium valproate in status epilepticus. Bladin, PF; Donnan, GA; Mihaly, GW; Miles, JL; Vajda, FJ, 1978)	0.26
" New knowledge of the pharmacokinetics of phenytoin has led to a better understanding of the drug's bioavailability and uses."	( Recent advances in drug therapy for epilepsy. Bruni, J, 1979)	0.26
" The absorption rate and fraction are very much dependent on the pharmaceutical preparation, and changes of brand may alter the plasma level of phenytoin in spite of unaltered dose."	( Clinical pharmacokinetics of anticonvulsants. Dam, M; Hvidberg, EF, 1976)	0.26
"05), and the absorption rate (Ka) was larger (P less than ."	( Circadian changes of valproate kinetics depending on meal condition in humans. Nakano, S; Ogawa, N; Ohdo, S, 1992)	0.28
" The bioavailability was not affected by the change in dosage regimen."	( [A single daily dose with valproic acid. A pharmacodynamic and clinical study]. Mamoli, B; Pelzl, G, 1992)	0.58
" Their effect on bioavailability was observed as an increase in plasma levels of the active substance, with areas under the plasma concentration/time curve of 396."	( Rectal bioavailability of water-soluble drugs: sodium valproate. Cerezo, A; Margarit, MV; Rodríguez, IC, 1991)	0.28
"The in vivo bioavailability of magnesium valproate (500 and 1000 mg) enteric-coated tablets has been compared with that of sodium valproate (Depakine) (500 and 1000 mg) enteric-coated tablets."	( Study of bioequivalence of magnesium and sodium valproates. Balbi, A; Mazzei, M; Sannita, WG; Sottofattori, E, 1991)	0.28
" For the 2 extravascular routes, the absolute bioavailability F, maximal plasma concentrations Cmax, times to peak Tmax and absorption coefficients Kabs were the same."	( Effects of administration route on valproate pharmacokinetics in the rabbit. Bourin, M; Guenzet, J; Kergueris, MF; Larousse, C; Ortega, A; Thomare, P, 1991)	0.28
" The complete oral bioavailability of VPD and the fact that the AUC of VPA obtained after oral administration of VPD was not higher than that obtained after the iv injection of VPD indicates that the gastrointestinal tract is not one of the metabolic sites of VPD to VPA conversion."	( The disposition of valpromide in rats and the isolated perfused rat liver. Bar-On, H; Bialer, M; Billig, H; Ziv, E, )	0.13
"The pharmacokinetics and bioavailability of valproic acid was compared in six healthy volunteers after single dose oral administration of 400 mg of the drug in tablet, capsule and syrup form in a crossover manner."	( Pharmacokinetics of valproic acid after administration of three oral formulations in healthy adults. Bano, G; Gupta, KL; Gupta, S; Raina, RK, 1990)	0.86
"05) and absorption rate constant (ka) tended to be larger (0."	( Chronopharmacokinetic study of valproic acid in man: comparison of oral and rectal administration. Nakano, S; Ogawa, N; Yoshiyama, Y, 1989)	0.56
"The relative bioavailability was measured for the 150-, 300-, and 600-mg enteric coated Leptilan tablets (valproic acid, sodium salt) using a new method."	( [Bioavailability of a valproic acid preparation. The relative bioavailability of enteric-resistant valproic acid preparations in tablet form with simultaneously administered tetradeuterated valproic acid as the bioavailability reference]. Hoffmann, F; Jancik, BC; von Unruh, GE, 1986)	0.8
" The Cmax and the AUC were lower with III than with IV, VI or VII but the extent of bioavailability (EBA) of III was about 80%."	( Pharmaceutical evaluation of hollow type suppositories. V. Preparation of valproic acid suppository and rectal absorption of valproic acid in rabbits. Matsumoto, M; Nishihara, S; Tone, Y; Watanabe, Y, 1986)	0.5
" Although rectal administration of sodium valproate (NaVPA) has been shown to be a possible alternative route, little is known about the bioavailability and local effects during repeated administration of NaVPA suppositories."	( Bioavailability of sodium valproate suppositories during repeated administration at steady state in epileptic children. Bourgeois, BF; Issakainen, J, 1987)	0.27
" The bioavailability of VPA following dosing of both ointment was above 97%."	( Percutaneous absorption of valproic acid and its plasma concentration after application of ointment. Ito, Y; Iwaki, M; Ogiso, T; Yamahata, T; Yamamoto, Y, 1987)	0.57
"The bioavailability of a film-coated tablet of valproate (VPA) in nonfasting volunteers was studied."	( Bioavailability of a film-coated tablet of valproate in nonfasting volunteers. Awaya, A; Furuyama, M; Horie, M; Ishikawa, T; Ohuchi, M; Okajima, K; Sobajima, H; Suchi, M; Wanibe, M; Yamaguchi, A, 1987)	0.27
" Following oral administration, the absolute bioavailability of VCD was 94 +/- 14%, and the terminal half-life was similar to that obtained after iv administration."	( Pharmacokinetics of a valpromide isomer, valnoctamide, in dogs. Bialer, M; Haj-Yehia, A, 1988)	0.27
" The mechanisms responsible for these effects have not been elucidated and possibly include decreased bioavailability or compliance, increased metabolic clearance, or decreased plasma protein binding."	( Effects of pregnancy on antiepileptic drug utilization. Levy, RH; Yerby, MS, 1985)	0.27
" The bioavailability of valproate from SHD enteric-coated tablets (Epival, Abbott-50711) and from sodium valproate enteric-coated tablets (Ergenyl) was compared in a single-dose, double-blind, crossover study."	( Single-dose kinetics and bioavailability of sodium-hydrogen divalproate. Anderson, P; Elwin, CE, 1985)	0.27
" Three of the formulations exhibited a more prolonged and uniform absorption rate and yielded more sustained serum levels after ingestion."	( Pharmacokinetic evaluation of novel sustained-release dosage forms of valproic acid in humans. Abramsky, O; Bialer, M; Dubrovsky, J; Friedman, M; Raz, I, )	0.37
" Carbamazepine is well absorbed and largely metabolized."	( Pharmacokinetics of antiepileptic drugs. Neuvonen, PJ; Tokola, RA, 1983)	0.27
" Although the absorption of DS was delayed, the bioavailability of VA capsules and DS tablets was equivalent."	( Gastrointestinal tolerance of divalproex sodium. Asconape, J; Karas, BJ; Penry, JK; Wilder, BJ, 1983)	0.27
"5 microgram/ml and provides the capability of conducting absolute bioavailability and pulsed dosing studies with deuterated drug analogues without a mass spectrometer."	( Resolution of valproic acid from deuterated analogues and their quantitation in plasma using capillary gas chromatography. Hoffman, DJ; Porter, WR, 1983)	0.63
" The relative bioavailability of the two compounds was similar across the group of patients, although there were marked differences between individual subjects."	( Pharmacokinetics of enteric-coated valproic acid. Albright, PS; Bruni, J; Suria, D, 1984)	0.54
" The average fraction of valpromide that was transformed to valproic acid (fm) ranged from 30-55 per cent after all the oral and parenteral administrations, except for the enteric-coated tablet, which showed a very low bioavailability of valpromide."	( Pharmacokinetics of valpromide in dogs after various modes of administration. Bialer, M; Rubinstein, A, )	0.37
" Several issues pertaining to the bioavailability of progabide were addressed: first-pass effect, incomplete dissolution, and dose and time dependency."	( Disposition of progabide and valproic acid following intraperitoneal administration in rhesus monkey. Bialer, M; Johno, I; Levy, RH; Nickelson, SA, 1984)	0.56
"As part of a comparative bioavailability investigation, the steady-state pharmacokinetics of the anticonvulsant valproate (given as the sodium salt and the free acid) were studied in 8 epileptic patients who had received long term therapy with the drug."	( Steady-state valproate pharmacokinetics during long term therapy. Eadie, MJ; Heazlewood, V; McKauge, L; Tyrer, JH, 1983)	0.27
"6 hr and the mean bioavailability was 100%."	( Meal-dependent absorption of enteric-coated sodium valproate. Akbaraly, R; Brachet-Liermain, A; Cenraud, B; Gomeni, R; Guyot, M; Levy, RH; Loiseau, P; Morselli, PL, 1980)	0.26
"The Michaelis-Menten pharmacokinetics and bioavailability of phenytoin were evaluated in children."	( Plasma levels and pharmacokinetics of antipileptic drugs in children. Miura, H, 1981)	0.26
"In six healthy volunteers the bioavailability of two valproic acid preparations (enteric coated tablets and slow-release formulation) was measured in a cross-over study during steady state."	( Bioavailability of a slow-release preparation of valproic acid under steady-state conditions. Klotz, U, 1982)	0.77
" The relative bioavailability of the amide was 81."	( Some clinical pharmacological aspects of n-dipropylacetamide. Di Perri, R; Pisani, F, 1980)	0.26
"The bioavailability of commercially available valproic acid (VPA) syrup was studied following rectal administration in both dogs and children."	( Bioavailability of rectally administered valproic acid syrup. Cloyd, JC; Kriel, RL, 1981)	0.79
" The bioavailability appeared to be the same for all the forms."	( Comparison of the effectiveness of several formulations of sodium valproate: tablets, enteric-coated capsules, solutions and rectal capsules. Avanzini, G; Battino, D; Biraghi, M; Cusi, C; Nespolo, A, 1982)	0.26
"The effects of three antacid products on the bioavailability of valproic acid were evaluated."	( Effects of three antacids on the bioavailability of valproic acid. Garnett, WR; May, CA; Pellock, JM; Small, RE, )	0.62
" We suggest that the interaction occurs at gastrointestinal level with a reduction of PHT and VPA oral bioavailability during antiviral treatment."	( Possible interaction between acyclovir and antiepileptic treatment. Parmeggiani, A; Posar, A; Riva, R; Rossi, PG, 1995)	0.29
" Bioavailability of CBZ was reduced by 29% in the presence of AMP, while that of SV was increased by about 8%."	( Aminophylline alters pharmacokinetics of carbamazepine but not that of sodium valproate--a single dose pharmacokinetic study in human volunteers. David, J; Joseph, T; Kulkarni, C; Vaz, J, 1995)	0.29
" HPE-101 increased the transdermal absorption rate of VPA by 80 times compared with the control."	( In vivo microdialysis for the transdermal absorption of valproate in rats. Goto, S; Ichikawa, M; Matsuyama, K; Nakashima, M; Satoh, S; Yano, T, 1994)	0.29
" Drug bioavailability was greatly affected as a result of microspheres formation."	( In vitro evaluation of cumulative release of valproic acid and vitamin E from hexadecanol microspheres. Part 2: Antiepileptic agents. De Caro, V; Di Stefano, V; Giannola, LI; Rizzo, MC, 1993)	0.55
" Also, the bioavailability relative to VPA alone was 86."	( Effect of cholestyramine resin on single dose valproate pharmacokinetics. Diskin, CJ; Malloy, MJ; Pennell, AT; Ravis, WR, 1996)	0.29
"Relative bioavailability of valproic acid after oral administration of 2 Convulsofin (test) tablets each containing 300 mg calcium valproate (263."	( Relative bioavailability of different valproic acid formulations. Diletti, E; Franke, G; Hoffmann, C; Scheuch, E; Siegmund, W; Zschiesche, M, 1995)	0.86
" Despite tissue damage sodium valproate was well absorbed intramuscularly."	( Pharmacokinetics and muscle histopathology of intramuscular valproate. DeToledo, J; Gallo, BV; Ramsay, RE; Slater, JD; Toledo, C, 1997)	0.3
"91 h), the absorption rate constant (0."	( Lack of kinetic interaction between valproic acid and citrus pectin. de Carvalho, D; Issy, AM; Lanchote, VL; Silva, HC, 1997)	0.57
" Bioequivalence with respect to extent and rate of absorption is therefore concluded for the comparison of fasting and non-fasting administration."	( Influence of food on the pharmacokinetics of a new multiple unit sustained release sodium valproate formulation. Retzow, A; Vens-Cappell, B; Wangemann, M, 1997)	0.3
" Also, the plasma t 1/2 (of carbamazepine was prolonged by two folds and bioavailability reduced by about 32% in presence of caffeine."	( Influence of caffeine on pharmacokinetic profile of sodium valproate and carbamazepine in normal human volunteers. David, J; Joseph, T; Kulkarni, C; Vaz, J, 1998)	0.3
"Two bioavailability studies were conducted in healthy male volunteers to determine the absorption characteristics of a new dosage form of sodium valproate consisting of sustained release pellets in a hard gelatine capsule."	( Pharmacokinetic characteristics of a new multiple unit sustained release formulation of sodium valproate. Retzow, A; Vens-Cappell, B; Wangemann, M, 1999)	0.3
" Population analysis was made with NONMEM program, assuming a one-compartment model, fixing the VPA absorption rate, bioavailability and distribution volume at values found in the literature."	( Valproate population pharmacokinetics in children. Buelga, DS; Domínguez-Gil, A; García Sánchez, MJ; Otero, MJ; Serrano, BB; Serrano, J, 1999)	0.3
" The newer anticonvulsants felbamate, lamotrigine, topiramate, and tiagabine have different hepatically-mediated drug-drug interactions, while the renally excreted gabapentin lacks hepatic drug-drug interactions but may have reduced bioavailability at higher doses."	( Metabolism and excretion of mood stabilizers and new anticonvulsants. Corá-Locatelli, G; Frye, MA; Ketter, TA; Kimbrell, TA; Post, RM, 1999)	0.3
"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
" Neurosteroid replacement is a potential approach to therapy, but natural neurosteroids have poor bioavailability and may be converted to metabolites with undesired progestational activity."	( Enhanced anticonvulsant activity of ganaxolone after neurosteroid withdrawal in a rat model of catamenial epilepsy. Reddy, DS; Rogawski, MA, 2000)	0.31
"A bioavailability study using three different doses was designed to assess the dose proportionality of a new multiple-unit sustained release formulation of sodium valproate."	( Study on the dose proportionality of the pharmacokinetics of sustained release sodium valproate. Mazur, D; Retzow, A; Vens-Cappell, B; Wangemann, M, 2000)	0.31
"Parameters determining the extent and rate of absorption (AUC and Cmax) increased proportionally with the dose of the new sustained release sodium valproate formulation."	( Study on the dose proportionality of the pharmacokinetics of sustained release sodium valproate. Mazur, D; Retzow, A; Vens-Cappell, B; Wangemann, M, 2000)	0.31
" The concepts of bioavailability and bioequivalence require further consideration."	( Is generic prescribing acceptable in epilepsy? Besag, FM, 2000)	0.31
" The absorption rate constant of copper (k(a)) which was estimated from the copper decline in the perfusion was unchanged without and with VPA (0."	( Valproic acid increases biliary copper excretion in the rat. Amioka, K; Kuzuya, T; Nabeshima, T, 2002)	1.76
" However, due to its poor bioavailability in vivo, the therapeutic use of butyrate is limited."	( Modulation of angiogenesis-related protein synthesis by valproic acid. Becker, U; Loitsch, S; Stein, J; Zgouras, D, 2004)	0.57
"001) difference in median values of the absorption rate constant was found between enteric-coated and sustained-release VAL formulations."	( Nonparametric population modeling of valproate pharmacokinetics in epileptic patients using routine serum monitoring data: implications for dosage. Bondareva, IB; Jelliffe, RW; Sokolov, AV; Tischenkova, IF, 2004)	0.32
"Conventional delayed-release, enteric-coated divalproex sodium tablet has an absolute bioavailability of approximately 100%."	( Absolute bioavailability and absorption characteristics of divalproex sodium extended-release tablets in healthy volunteers. Cavanaugh, JH; Dutta, S; Reed, RC, 2004)	0.32
" The bioavailability of novel 250 mg divalproex-ER formulations, under development to allow greater flexibility in dosing, was compared with the available 500 mg divalproex-ER in a single-dose, fasting and nonfasting, randomized, open-label, crossover study in healthy adult volunteers."	( Comparison of the bioavailability of 250 and 500 mg divalproex sodium extended-release tablets in healthy volunteers. Dutta, S; Lee, LL; O'Dea, R; Zhang, Y, 2004)	0.32
" A meta-analysis of divalproex-ER/divalproex relative bioavailability across five studies under different meal conditions and divalproex dosing frequencies was performed."	( Bioavailability of divalproex extended-release formulation relative to the divalproex delayed-release formulation. Dutta, S; Zhang, Y, 2004)	0.32
" High-fat breakfast or yogurt did not modify either the bioavailability or pharmacokinetic profile of valproate MR granules."	( Bioequivalence of a new sustained-release formulation of sodium valproate, valproate modified-release granules, compared with existing sustained-release formulations after once- or twice-daily administration. Alvarez, JC; Dulac, O, 2005)	0.33
" The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability and bioequivalence studies."	( Liquid chromatography/electrospray ionization mass spectrometry method for the quantification of valproic acid in human plasma. Chidambara, J; Koteshwara, M; Kumar, BR; Manoj, S; Ramakrishna, NV; Santosh, M; Vishwottam, KN, 2005)	0.55
" Oral forms are almost completely bioavailable but the rate of absorption varies between formulations."	( Valproate as a mainstay of therapy for pediatric epilepsy. Guerrini, R, 2006)	0.33
" It showed a beneficial pharmacokinetic profile in rats, having a high oral bioavailability of 75% and satisfactory values of clearance and volume of distribution."	( Anticonvulsant activity, neural tube defect induction, mutagenicity and pharmacokinetics of a new potent antiepileptic drug, N-methoxy-2,2,3,3-tetramethylcyclopropane carboxamide. Bialer, M; Finnell, RH; Lamb, JG; Sobol, E; White, HS; Wlodarczyk, BJ; Yagen, B, 2007)	0.34
" The comparable AUC across the five formulations, when corrected for bioavailability differences, demonstrates that formulation primarily affects the drug-release and in vivo absorption of VPA."	( Distinct absorption characteristics of oral formulations of valproic acid/divalproex available in the United States. Dutta, S; Reed, RC, 2007)	0.58
" 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
" Both volume and absorption rate constant were fixed (14 L and 1 hr, respectively)."	( Population pharmacokinetics of valproic acid concentrations in elderly nursing home residents. Ahn, JE; Birnbaum, AK; Brundage, RC; Conway, JM; Hardie, NA; Leppik, IE, 2007)	0.63
" Oral administration within the LCT solution caused more than a 3-fold increase in DP-VPA bioavailability in comparison to the MCT solution."	( The oral absorption of phospholipid prodrugs: in vivo and in vitro mechanistic investigation of trafficking of a lecithin-valproic acid conjugate following oral administration. Dahan, A; Duvdevani, R; Elmann, A; Finkelstein, E; Hoffman, A; Shapiro, I, 2008)	0.55
" VPA was selected since it is currently used in clinical practice and its pharmacokinetic, pharmacodynamic and bioavailability are known."	( Valproic acid sensitizes K562 erythroleukemia cells to TRAIL/Apo2L-induced apoptosis. Iacomino, G; Medici, MC; Russo, GL, )	1.57
"The study examined relative bioavailability of a novel valproic acid (VPA) delayed-release (DR) soft gelatin capsule formulation to divalproex sodium DR tablet under fasting conditions and the effect of food on the bioavailability of the VPA DR soft gelatin capsule."	( Bioequivalence studies of a new valproic acid delayed-release capsule and divalproex sodium delayed-release tablet. Fang, Q; Garikipati, V; Toops, DS, 2008)	0.88
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."	( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination. Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010)	0.36
" Our findings also suggest that ethnic traits may affect carnitine bioavailability as well as cognitive outcomes in this clinical context."	( Clinical outcomes and low-dose levocarnitine supplementation in psychiatric inpatients with documented hypocarnitinemia: a retrospective chart review. Abramson, RK; Cuturic, M; Hardin, JW; Moran, RR, 2010)	0.36
" Using Monte Carlo simulation, our results predict a way to maximize the operational multiple dosing half lives relative to the terminal half life by using a first-order absorption rate constant close to the terminal elimination rate constant in the design of extended release dosage forms."	( Intermittent drug dosing intervals guided by the operational multiple dosing half lives for predictable plasma accumulation and fluctuation. Benet, LZ; Grover, A, 2011)	0.37
"3% bioavailability for enteral liquid applications."	( Levetiracetam compared to valproic acid: plasma concentration levels, adverse effects and interactions in aneurysmal subarachnoid hemorrhage. Bjeljac, M; Keller, E; Mink, S; Muroi, C; Seule, M, 2011)	0.67
"Though this finding needs further verification, the enteral liquid application of levetiracetam seems to be associated with lower bioavailability than the common oral application of levetiracetam."	( Levetiracetam compared to valproic acid: plasma concentration levels, adverse effects and interactions in aneurysmal subarachnoid hemorrhage. Bjeljac, M; Keller, E; Mink, S; Muroi, C; Seule, M, 2011)	0.67
" Herein, we tested if valproic acid and the novel orally bioavailable HDACi, AR-42 reduced the proliferation of ATL cell lines by promoting apoptosis and histone hyperacetylation."	( Efficacy of novel histone deacetylase inhibitor, AR42, in a mouse model of, human T-lymphotropic virus type 1 adult T cell lymphoma. Chen, CS; Fernandez, SA; Lairmore, MD; Landes, K; Sargeant, A; Zimmerman, B, 2011)	0.68
" Future studies are needed to determine whether VPA increases TMZ bioavailability or acts as an inhibitor of histone deacetylases and thereby sensitizes for radiochemotherapy in vivo."	( Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma. Belanger, K; Bogdahn, U; Brandes, AA; Cairncross, JG; Forsyth, P; Gorlia, T; Lacombe, D; Macdonald, DR; Mason, W; Mirimanoff, RO; Rossetti, AO; Stupp, R; van den Bent, MJ; Vecht, CJ; Weller, M, 2011)	0.68
"The purpose of this study was to compare the pharmacokinetics and bioavailability of two commercial brands of delayed release divalproex sodium (CAS 76584-70-8) tablets in healthy male Iranian volunteers in fasted state."	( Fasted state bioavailability of two delayed release formulations of divalproex sodium in healthy Iranian volunteers. Ghanbarzadeh, S; Hamishehkar, H; Nemati, M; Valizadeh, H; Zakeri-Milani, P, 2011)	0.37
" Weight affected both volume of the central compartment and the absorption rate constant."	( Sex related differences on valproic acid pharmacokinetics after oral single dose. Derendorf, H; Fagiolino, P; Ibarra, M; Vázquez, M, 2013)	0.69
"If these data translate to the overall transport and subsequent bioavailability of folates, noncompetitive inhibition of the folate receptors by VPA may serve to lower the bioavailable folates in VPA treated mothers."	( Brief report novel mechanism for valproate-induced teratogenicity. Fathe, K; Finnell, RH; Palacios, A, 2014)	0.4
" Bioavailability after oral administration vs."	( Drug Pharmacokinetics Determined by Real-Time Analysis of Mouse Breath. Bregy, L; Brown, SA; Dallmann, R; Detmar, M; Hollmén, M; Kohler, M; Li, X; Martinez-Lozano Sinues, P; Proulx, S; Zenobi, R, 2015)	0.42
" The oral bioavailability of paliperidone was increased by an estimated 51% (Cmax ) and 51%-52% (AUCs) when coadministered with divalproex sodium ER."	( Drug-Drug Interaction Studies of Paliperidone and Divalproex Sodium Extended-Release Tablets in Healthy Participants and Patients with Psychiatric Disorders. Ariyawansa, J; Berwaerts, J; Coppola, D; De Meulder, M; Remmerie, B, 2016)	0.43
" We also investigated the changes in the central carbon metabolism of HepaRG cells exposed to orally bioavailable concentrations of both drugs."	( In Silico Modeling for the Prediction of Dose and Pathway-Related Adverse Effects in Humans From In Vitro Repeated-Dose Studies. Bucher, J; Heinzle, E; Klein, S; Maggioni, S; Mauch, K; Mueller, D; Niklas, J; Noor, F; Shevchenko, V, 2016)	0.43
" The change of the drug formulation resulted in a several times higher bioavailability of the drug and a partial improvement of the patient's clinical condition."	( Valproic acid malabsorption in 30 year-old female patient - Case study. Jopowicz, A; Kurkowska-Jastrzębska, I; Piechal, A, )	1.57
" However, a low bioavailability beside the bad compliance should be considered when the minimal level is extremely low during therapy."	( Valproic acid malabsorption in 30 year-old female patient - Case study. Jopowicz, A; Kurkowska-Jastrzębska, I; Piechal, A, )	1.57
" The mean serum concentrations and the mean serum concentrations per weight per daily dose per bioavailability (F) of anti-epileptic drugs (AEDs) before and during the treatment were assessed."	( Effect of ketogenic diet and other dietary therapies on anti-epileptic drug concentrations in patients with epilepsy. Chang, MJ; Heo, G; Kim, SH, 2017)	0.46
"This study was aimed to investigate the potential of formulated valproic acid-encapsulated nanoemulsion (VANE) to improve the brain bioavailability of valproic acid (VPA)."	( Characterisation, in-vitro and in-vivo evaluation of valproic acid-loaded nanoemulsion for improved brain bioavailability. Basri, HB; Kirby, BP; Stanslas, J; Tan, SF, 2017)	0.94
" Given the same extent of in-vitro BBB permeation of VPA and VANE, the higher bioavailability of VANE in brain was believed to have due to higher concentration of VANE in blood."	( Characterisation, in-vitro and in-vivo evaluation of valproic acid-loaded nanoemulsion for improved brain bioavailability. Basri, HB; Kirby, BP; Stanslas, J; Tan, SF, 2017)	0.7
"Nanoemulsion containing VPA has alleviated the cytotoxic effect of VPA and improved the plasma and brain bioavailability for parenteral delivery of VPA."	( Characterisation, in-vitro and in-vivo evaluation of valproic acid-loaded nanoemulsion for improved brain bioavailability. Basri, HB; Kirby, BP; Stanslas, J; Tan, SF, 2017)	0.7
" In this paper, we have investigated the cytotoxic interaction of ERL and valproic acid (VA) in ERL-resistant NSCLC cells and developed a liquisolid formulation of ERL-VA for improving oral bioavailability of ERL."	( Erlotinib-Valproic Acid Liquisolid Formulation: Evaluating Oral Bioavailability and Cytotoxicity in Erlotinib-Resistant Non-small Cell Lung Cancer Cells. Bagde, A; Doddapaneni, R; Patel, K; Patki, M; Sekar, V; Singh, M, 2019)	1.15
"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
" Careful selection of appropriate in vitro and in vivo models to demonstrate increased radiosensitivity and suitable bioavailability are then necessary to prove that a drug warrants advancement to clinical investigation."	( Bench to bedside radiosensitizer development strategy for newly diagnosed glioblastoma. Camphausen, K; Degorre, C; Mathen, P; Tofilon, P, 2021)	0.62
" Their stability, natural structure, composition, and bioavailability make them good candidates as drug vehicles."	( Sustained release of sulforaphane by bioactive extracellular vesicles for neuroprotective effect on chick model. Saeidifar, M; Shahlaei, M; Zamanian, A, 2022)	0.72
" VPM summary of product characteristics and pharmacokinetic studies revealed a lower bioavailability (80% vs."	( Valproate, divalproex, valpromide: Are the differences in indications justified? Besson, VC; Blaise, N; Bloch, V; Chouchana, M; Delage, C; Etain, B; Hagenimana, M; Palayer, M; Smati, J, 2023)	0.91
"Cytochrome P450 3A4 (CYP3A4) is involved in first-pass metabolism in the small intestine and is heavily implicated in oral drug bioavailability and pharmacokinetics."	( The Effect of Vitamin D3 and Valproic Acid on the Maturation of Human-Induced Pluripotent Stem Cell-Derived Enterocyte-Like Cells. Kato, Y; Koike, M; Kume, S; Leo, S; Shiraki, N; Tsuchiya, K; Wu, Y; Yokota, M; Yui, S, 2023)	1.2
" A major challenge lies in the lack of knowledge about the bioavailability and pharmacodynamic effects of bioactive compounds in this model organism."	( Pharmacometabolic Effects of Pteryxin and Valproate on Pentylenetetrazole-Induced Seizures in Zebrafish Reveal Vagus Nerve Stimulation. Budzyńska, B; Gertsch, J; Kozioł, E; Lee, SM; Morozova, V; Pellegata, D; Skalicka-Woźniak, K; Skiba, A, 2023)	0.91

Dosage Studied

Once-daily administration of divalproex sodium extended-release tablets (doses ranged from 250 to 1750 mg) in older children and adolescents produced relatively flat plasma valproic acid concentration-time profiles over the entire 24-hour dosing interval. Cosmetic side effects leading to dosage change or discontinuation occurred most frequently with pregabalin and Valproic Acid compared with all other AEDs.

Excerpt	Relevance	Reference
" The 3 drugs also show differences in elimination rate, which make it desirable to give valproate 3 times a day and clonazepam twice a day, whereas ethosuximide could reasonably be given once daily without undesirably wide fluctuations in plasma drug level over the dosage interval."	( Pharmacokinetics of drugs used for petit mal 'absence' epilepsy. Eadie, MJ; McKauge, L; Smith, GA; Tyrer, JH, 1977)	0.26
" It is useful alone or as an adjunct to other anticonvulsants and may allow the dosage of the latter to be reduced."	( Valproic acid (Depakene). A new anticonvulsant agent. Lewis, JR, 1978)	1.7
" The following results were found while DPA was administered in a relatively high dosage with a mean of 48 mg/kg body weight/day and ranging from 7 to 125 mg/kg/day."	( Treatment of childhood epilepsy with dipropylacetic acid (DPA). Blaschke, E; Fehr, R; Lagenstein, I; Rothe, M; Sternowsky, HJ, 1978)	0.26
" A twice daily dosage regime was satisfactory."	( Sodium valproate (Epilim) in epilepsy: a trial. Briant, RH; Foote, SE; Wallis, WE, 1978)	0.26
" The occurrence of side effects or possible side effects of valproic acid led to a dosage reduction of discontinuation of the compound in 25% of the patients."	( [Antiepileptic therapy with valproinic acid. Correlations of side effects and serum levels of valproinic acid]. Fröscher, W; Gugler, R; Schulz, HU, 1979)	0.5
" It is suggested that the great fluctuations of the plasma concentrations within a dosing interval may be minimized by special galenic formulations."	( Pharmacokinetic studies with valproic acid in man. Klotz, U, 1977)	0.55
" 4) Dosage and plasma levels did not appear to show a close correlation."	( Plasma sodium valproate levels and clinical response in epilepsy. Anthony, M; Hinterberger, H; Lance, JW, 1977)	0.26
" In contrast, an acceleration of the growth and a reduction of the survival time were observed in females dosed with alpha-MPG or DPA."	( [Effect of alpha-mercaptopropionylglycine (alpha-MPG) and sodium dipropylacetate (DPA) on antibody formation (IV). Tumor immunity (author's transl)]. Koda, A; Mori, H; Saiki, I, 1978)	0.26
" Tremor was ameliorated in two cases when the dosage was reduced."	( Tremor due to sodium valproate. Dennis, PD; Hyman, NM; Sinclair, KG, 1979)	0.26
" The abnormal values returned promptly to normal when the drug therapy was discontinued or the dosage reduced."	( A direct hepatotoxic effect of valproic acid. McLain, LW; Sussman, NM, 1979)	0.55
" The results indicate that a proportional rise in plasma sodium valproate levels can be expected following dosage increments in an individual patient."	( Sodium valproate: dose-plasma level relationships and interdose fluctuations. Bladin, PF; Mihaly, GW; Miles, JL; Morris, PM; Vajda, FJ, 1978)	0.26
" Serum drug concentrations were measured during 4 dosing intervals, once before and 3 times after beginning carbamazepine."	( Effects of carbamazepine on valproic acid kinetics in normal subjects. Bowdle, TA; Cutler, RE; Levy, RH, 1979)	0.55
" Tissue distribution studies in rats sacrificed 20 and 90 min after dosage with [14C] NaVPA (150 mg/kg) showed that the drug concentration was highest in blood, moderate in liver, kidney, heart and lung and low in brain, fat, testis and skeletal muscle."	( Disposition of valproic acid in the rat: dose-dependent metabolism, distribution, enterohepatic recirculation and choleretic effect. Dickinson, RG; Gerber, N; Harland, RC; Ilias, AM; Kaufman, SN; Lynn, RK; Rodgers, RM, 1979)	0.61
" Dosage varied from 23 to 54mg/kg and twice-daily administration was usual."	( Treatment of generalized epilepsies of childhood and adolescence with sodium valproate ("epilim"). Clark, JE; Jeavons, PM; Maheshwari, MC, 1977)	0.26
"79 patients with primary generalized epilepsies have been treated with DPA in a medium dosage of 51 mg/kg bodyweight/day, range 14 to 125 mg/kg/day, for a medium time of 22 months, range 2 to 49 months."	( [The treatment of primary generalized epilepsies with dipropyl acetate (DPA)]. Blaschke-Zimmermann, E; Fehr, R; Iffland, E; Lagenstein, I; Sternowsky, HJ, 1977)	0.26
" Combined treatment with other anticonvulsant drugs decreases the half-life and more frequent dosing may be necessary."	( Clinical pharmacokinetics of anticonvulsants. Dam, M; Hvidberg, EF, 1976)	0.26
" In rather short time reliable information concerning indication, compatibility and dosage can be received."	( [Austrian complex-study on dipropylacetate. Pediatric experiences]. Groh, Ch; Rosenmayr, FW, 1976)	0.26
" In monopharmacy patients, plasma NH3 levels did not depend on age, VPA dosage or serum levels."	( Is 2-propyl-4-pentenoic acid, a hepatotoxic metabolite of valproate, responsible for valproate-induced hyperammonemia? Fukushima, Y; Hirano, T; Ishida, M; Kaneko, S; Koide, N; Kondo, T; Muranaka, H; Nakata, S; Otani, K; Yokoyama, M, )	0.13
" On the basis of these considerations and clinical reports describing the use of these drugs, we make dosage recommendations to enable the practitioner to individualize therapeutic regimens."	( Drugs used in the management of trigeminal neuralgia. Patsalos, PN; Zakrzewska, JM, 1992)	0.28
" The usual phenytoin (PHT) dosage in adults is 4-6 mg/kg per day, but children may need a dosage three to five times higher."	( Metabolism of antiepileptic medication: newborn to elderly. Leppik, IE, 1992)	0.28
" Because of the rapid conversion of the prodrugs to the parent drug, levels of VPA in plasma after administration of the prodrugs peaked at 6-26 min after dosing and did not yield an in vivo sustained-release dosage profile."	( Pharmacokinetic analysis of ester prodrugs of valproic acid. Bialer, M; Hadad, S; van der Kleijn, E; Vree, TB, 1992)	0.54
"6%) and without significant dose dependency, suggesting that this parameter may be useful for guiding VPA dosage adjustment and monitoring patient compliance."	( Relationship between serum concentration and dose of valproic acid during monotherapy in adult outpatients. Oles, KS; Penry, JK; Tisdale, JE; Tsuyuki, RT, 1992)	0.53
" Using whole rat embryo cultures, the simultaneous addition of methionine and sodium valproate to the medium provided no protection from neural tube defects, nor did the addition of methionine to a medium of serum obtained from rats previously dosed with sodium valproate."	( Methionine decreases the embryotoxicity of sodium valproate in the rat: in vivo and in vitro observations. Klein, NW; Nosel, PG, 1992)	0.28
" The result showed that both drugs were effective in most cases at modest dosage without causing notable psychological effects 12 months into treatment."	( Psychological effects of sodium valproate and carbamazepine in epilepsy. Stores, G; Styles, E; Williams, PL; Zaiwalla, Z, 1992)	0.28
"This study was performed to investigate the influence of the dosing route on chronopharmacological aspect of valproic acid (VPA) in mice, comparing the oral and rectal route."	( Chronopharmacological study of valproic acid in mice: comparison of oral and rectal administration. Nakano, S; Ogawa, N; Ohdo, S; Yoshiyama, Y, 1992)	0.78
" Valproate plasma levels and performances in attention and vigilance tasks were monitored during a 12-h period (daytime), both during monotherapy of conventional valproate (VPA) and 4 weeks after switching to a similar dosage of VPA-CR taken once daily."	( Conventional and controlled release valproate in children with epilepsy: a cross-over study comparing plasma levels and cognitive performances. Bakker, AM; Brouwer, OF; Edelbroek, PM; Jennekens-Schinkel, A; Lanser, JB; Peters, AC; Pieters, MS; Stijnen, T; van Geel, AA, 1992)	0.28
" Compliance may be enhanced because of the more convenient dosing schedules and the high degree of patient and parent acceptance."	( Comparison of sprinkle versus syrup formulations of valproate for bioavailability, tolerance, and preference. Cloyd, JC; Jancik, JT; Jones-Saete, CM; Kriel, RL; Ong, BY; Remmel, RP, 1992)	0.28
" However, the size of chronic treatment dose was important for the rate and degree of tolerance development, since an increase of dosage to 150 mg/kg 3 times daily resulted in significant anticonvulsant effects throughout the period of treatment with almost no indication of tolerance."	( Pharmacokinetics, anticonvulsant efficacy, and adverse effects of trans-2-en-valproate after acute and chronic administration in amygdala-kindled rats. Hönack, D; Löscher, W; Rundfeldt, C, 1992)	0.28
" Without changing the total daily dosage the once-daily treatment proved to be of at least equal clinical efficacy."	( [A single daily dose with valproic acid. A pharmacodynamic and clinical study]. Mamoli, B; Pelzl, G, 1992)	0.58
" Urine was collected for one dosage interval (12 h) at steady state for each dose and assayed for 15 VPA metabolites by gas chromatography/mass spectrometry (GCMS)."	( Effect of valproate dose on formation of hepatotoxic metabolites. Acheampong, AA; Anderson, GD; Levy, RH; Wilensky, AJ, )	0.13
" A significant improvement was found in the symptomatology of these patients, but relapses occurred when CLZ dosage was reduced."	( Sodium valproate and clonazepam for treatment-resistant panic disorder. Fontaine, R; Ontiveros, A, 1992)	0.28
"5 and year-old epileptic boy with severe acute pancreatitis which appeared 39 months after starting treatment with sodium valproate (VAP) at a daily dosage of 26."	( [Acute pancreatitis caused by sodium valproate. Review of the literature apropos of a case in a child]. Boussard, N; de Miscault, G; Rose, E; Thome, M, 1991)	0.28
" Rats were dosed ip with 100 mg/kg of VPA, 4-ene-, or 2,4-diene-VPA, and methylated bile and urine extracts were analyzed by LC/MS/MS and GC/MS, respectively."	( Identification and characterization of the glutathione and N-acetylcysteine conjugates of (E)-2-propyl-2,4-pentadienoic acid, a toxic metabolite of valproic acid, in rats and humans. Abbott, F; Farrell, K; Kassahun, K, )	0.33
"0001) inverse correlation between the daily VPA dosage and the VPA dose ratio (concentration/dose or 1/clearance)."	( Valproic acid dosages necessary to maintain therapeutic concentrations in children. Cox, S; Hayes, J; Suzuki, Y; Walson, PD, 1991)	1.72
" Recent experiments demonstrate that an appropriate dosing regimen (consecutive doses of VPA on day 9 of gestation) can also result in a low incidence of spina bifida aperta, and a high incidence of spina bifida occulta in the mouse as a potential animal model."	( Valproic acid-induced neural tube defects in mouse and human: aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms. Ehlers, K; Hauck, RS; Nau, H, 1991)	1.72
"A comment aid system for therapeutic drug monitoring (TDM), which produces the primary comment on the dosage regimen of valproate, was developed."	( [Development and evaluation of the comment aid system for therapeutic drug monitoring. I. Application to valproate]. Iga, T; Kohda, Y; Ohtani, H; Yamamoto, K, 1991)	0.28
" Plasma concentrations of paroxetine at steady state (8-147 ng/ml) were in the normal range for a 30-mg daily dosing regimen."	( No influence of the antidepressant paroxetine on carbamazepine, valproate and phenytoin. Andersen, BB; Dam, M; Kristensen, HB; Lund, J; Mengel, H; Mikkelsen, M; Pedersen, B; Vesterager, A, )	0.13
" Carbamazepine in moderate dosage adversely affected memory, but sodium valproate and phenytoin did not."	( Cognitive impairment in new cases of epilepsy randomly assigned to carbamazepine, phenytoin and sodium valproate. Berg, I; Butler, R; Forsythe, I; McGuire, R, 1991)	0.28
" They were divided into 3 groups treated with Mg-VPA in dosage of 800 mg, 600 mg and 400mg respectively at 7 pm in an attempt to find out an appropriate dosage with which the effective serum level could be maintained in the night time for those patients with only nocturnal seizures."	( [Appropriate dosage for maintaining effective serum level at night after taking one dose of magnesium valproate with separate measurements of serum Mg++ concentration]. Yan, CS, 1991)	0.28
"We describe the case of a 26 years old woman in chronic therapy with phenobarbital, carbamazepine, valproic acid (VPA) and clonazepam who showed a hyperammonemic encephalopathy after an increase in dosage of VPA."	( State of stupor from valproic acid during chronic treatment: case report. Buffa, C; Gentile, S; Ravetti, C; Sacerdote, I, 1991)	0.82
" Serum valproate concentrations were measured three times weekly; an unblinded investigator then adjusted dosage to produce serum concentrations between 50 and 100 mg/L."	( Valproate in the treatment of acute mania. A placebo-controlled study. Hudson, JI; Keck, PE; McElroy, SL; Pope, HG, 1991)	0.28
" To assess potential use of E-delta 2-VPA as an alternate to VPA, a dose-response study comparing the anticonvulsant activity and neurotoxicity of E-delta 2-VPA and VPA was conducted in rats using the intravenous (i."	( Comparative pharmacodynamics and brain distribution of E-delta 2-valproate and valproate in rats. Semmes, RL; Shen, DD, )	0.13
" The specific topics include: the placental transfer of valproic acid; the teratogenic potential; structure-teratogenicity and dose-response relationships; species and strain differences; biochemical changes evoked by the drug in the fetus."	( Developmental toxicity of valproic acid. Cotariu, D; Zaidman, JL, 1991)	0.83
"Free plasma level/dose ratio of valproic acid (L/D-F) can be more effective than total plasma level/dose ratio (L/D-T) in adjusting dosage regimens."	( Total and free valproic acid: plasma level/dose ratio in monotherapy. Abadín, JA; Durán, JA; Sánchez, A; Serrano, JS, 1991)	0.92
" In order to define the minimal dosage of fentanyl required, the MD was titrated according to increases or decreases in the heart rate and/or mean arterial pressure exceeding 15 per cent of baseline ward values."	( Anticonvulsant therapy increases fentanyl requirements during anaesthesia for craniotomy. Modica, PA; Spitznagel, EL; Tempelhoff, R, 1990)	0.28
" Nulliparous female CD-1 mice were dosed intraperitoneally on day 8 of gestation with 340 mg/kg of sodium valproate."	( Teratogenic effects on the neuroepithelium of the CD-1 mouse embryo exposed in utero to sodium valproate. De Philip, RM; Paulson, RB; Sucheston, ME; Turner, S, 1990)	0.28
" Blood and urine samples in the studies were collected during a dosing interval at steady state."	( Effects of polytherapy with phenytoin, carbamazepine, and stiripentol on formation of 4-ene-valproate, a hepatotoxic metabolite of valproic acid. Acheampong, A; Anderson, GD; Baillie, TA; Friel, PN; Guyot, M; Levy, RH; Loiseau, P; Rettenmeier, AW; Tor, J; Wilensky, AJ, 1990)	0.48
"To determine the absorption characteristics of a new dosage form of divalproex sodium consisting of coated particles in a pull-apart capsule (Depakote Sprinkle, Abbott Laboratories, North Chicago, IL), two absorption studies were conducted in adult volunteers."	( Absorption characteristics of a new valproate formulation: divalproex sodium-coated particles in capsules (Depakote Sprinkle). Brinker, DR; Carrigan, PJ; Cavanaugh, JH; Cloyd, JC; Lamm, JE, 1990)	0.28
" Our results suggest that the therapeutic serum range for seizures is valid for psychiatric patients but that the usual suggested oral dosage is often inadequate."	( Therapeutic levels of valproate for psychosis. Erickson, W; Kluznik, J; Merrill, R; VanValkenburg, C, 1990)	0.28
" Eighty-four patients had been established on treatment with a single anticonvulsant drug (35 carbamazepine (CBZ), 30 sodium valproate (VPA), 19 phenytoin (PHT)) at unaltered dosage for the previous 3 months."	( Cognitive function in adult epileptic patients established on anticonvulsant monotherapy. Brodie, MJ; Butler, E; Gillham, RA; Larkin, JG; Wiedmann, KD; Williams, N, 1990)	0.28
" These findings should therefore be considered when defining dosage regimens or interpreting serum drug concentrations."	( Analysis of the factors influencing anti-epileptic drug concentrations--valproic acid. Aoyama, T; Higuchi, S; Hirata, K; Ieiri, I; Yamada, H, 1990)	0.51
" Increasing the dosage raises the peak serum level and also increases the duration of time during which a minimum effective serum concentration is obtained."	( The scope and use of valproate in epilepsy. Dean, JC; Penry, JK, 1989)	0.28
" Mean VPA dosage was 16."	( The effect of carbamazepine on valproic acid disposition in adult volunteers. Abbott, FS; Burton, RW; Farrell, K; Kassahun, K; Orr, JM; Panesar, SK, 1989)	0.56
"Starting from Valproat dosage recommendations and serum levels and patient risk from acute hepatic failure, the results of our therapeutic service are set forth."	( [Valproate dosage]. Meyer, FP; Walther, H, 1989)	0.28
" The technique is simple and rapid: 4 anticonvulsants are simultaneously extracted and dosed, valproic acid, only has to be dosed lonely."	( [Plasma determination of 7 common drugs by high performance liquid chromatography]. Baty, C; Jambou, J; Leducq, B; Richard, L, 1989)	0.5
" The dose-response curve for NH4Cl was affected by simultaneous subcoma doses of VP and OA but not by PB."	( Valproic acid induction of coma in rats: synergism with NH4+ and pentobarbital. Lyftogt, C; Zieve, L, 1989)	1.72
" Dosage increases may be necessary, and serum concentrations should be monitored."	( Absorption of valproic acid suppositories in human volunteers. Carlson, GH; Graves, NM; Holmes, GB; Kriel, RD; Remmel, RP; Rosenfeld, WE, 1989)	0.64
" When the drug was repeatedly coadministered with DPH or CBZ, the initial VPA elimination from plasma up to 1 h after dosing was less than with VPA alone, while PB significantly enhanced the disappearance of VPA."	( Effects of anticonvulsants on plasma levels and entero-hepatic circulation of valproic acid and on hepatic drug metabolizing enzyme activities in rats. Horibe, Y; Ito, Y; Iwaki, M; Ogiso, T; Yoneda, I, 1989)	0.51
" Dosage adjustments and alterations in therapeutic regimen were allowed and another Cminss was measured after 1 to 12 months."	( Usefulness of a single-dose prediction model for the determination of long-term maintenance therapy of valproic acid. Garnett, WR; Pellock, JM; Pugh, CB, 1989)	0.49
" During EEG recording of wake-sleep cycle valporoic acid was shown to produce hypnotic action dependent on drug dosage in high active and low active animals."	( [The effect of valproic acid on sleep structure and ethanol consumption in rats with various types of individual reactivity before and after stress exposure]. Mdzinarishvili, AL; Molodavkin, GA; Voronina, TA, 1989)	0.63
" Two NaVP-filled Alzet osmotic minipumps were implanted subcutaneously on day 5 of gestation for continuous delivery of a total daily dosage of 850 mg/kg for 7 days."	( Effects of sodium valproate and oxygen on the craniofacial skeletal pattern in the CD-1 mouse embryo. Hayes, TG; Paulson, RB; Sucheston, ME; Weiss, HS, 1989)	0.28
" VPA was started in increasing dosage until infantile spasms were controlled or a maximum dose of 100 mg/kg/day was reached."	( Therapy of infantile spasms with valproate: results of a prospective study. Michael, T; Nau, H; Siemes, H; Spohr, HL, )	0.13
" In the case of diazepam, clonazepam, ethosuximide or trimethadione, the TE/TF ratio was decreased dose-dependently, but the slope of the dose-response regression line was less steep than that obtained by the administration of PB, PNT, CBZ, VPA or primidone."	( [The correlation between concentrations of anticonvulsive drugs in the brain and various parameters of maximal electroshock seizures in mice]. Kishita, C, 1986)	0.27
" The two cortical sites were distinguished by significantly different dose-response curve slopes for the suppression of afterdischarge duration by PHT, CBZ and VPA, which suggests more than one mechanism of action for these drugs."	( Differential antiepileptic sensitivity between cortical sites in the rat. Iragui, VJ; Kalichman, MW; Moss, KA, )	0.13
" Maternal pharmacokinetic parameters and plasma metabolites were determined for VPA on the first and last day of dosing for the 10X dose group."	( Predicting the human teratogenic potential of the anticonvulsant, valproic acid, from a non-human primate model. Cukierski, MA; Hendrickx, AG; Mast, TJ; Nau, H, 1986)	0.51
" Although dosage remained the same, serum concentrations decreased during pregnancy to therapeutic levels (33."	( Fetal growth, major malformations, and minor anomalies in infants born to women receiving valproic acid. Deichl, A; Hartmann, AM; Helge, H; Jäger-Roman, E; Jakob, S; Koch, S; Nau, H; Rating, D; Steldinger, R, 1986)	0.49
" This result has to be taken into account when dose-response relationships are evaluated."	( Pharmacokinetic aspects of drug effects in vitro: effects of serum protein binding on concentration and teratogenicity of valproic acid and 2-en-valproic acid in whole embryos in culture. Klug, S; Lewandowski, C; Nau, H; Neubert, D, 1986)	0.48
" One group (n = 6) received sodium valproate (1,100 mg/day) for 2 weeks, while the other group (n = 6) was given, for the same period, a dosage of VPM (1,200 mg/day) expected to produce VPA levels equivalent to those achieved with valproate."	( Sodium valproate and valpromide: differential interactions with carbamazepine in epileptic patients. Fazio, A; Gitto, C; Oteri, G; Perucca, E; Pisani, F; Ruello, C; Russo, F, )	0.13
" Photosensitivity disappeared in 44 of 65 patients at a mean dosage of VPA at 21."	( The prognosis of photosensitivity. Bishop, A; Harding, GF; Jeavons, PM, )	0.13
" Urine was also collected over the final dosing interval."	( Accumulation and washout kinetics of valproic acid and its active metabolites. Ermer, JC; Gengo, FM; McHugh, WB; Pollack, GM; Shen, DD, )	0.4
" The findings were related to previous diagnostic and dosage research."	( Effect of sodium valproate on psychomotor performance in children as a function of dose, fluctuations in concentration, and diagnosis. Aman, MG; Paxton, JW; Turbott, SH; Werry, JS, )	0.13
" We monitor free and total VPA at minimum and maximum along with evaluation of side effects and seizures for better interpretation of dosage requirements."	( Variable free and total valproic acid concentrations in sole- and multi-drug therapy. Bennett, DM; Cramer, JA; Mattson, RH; Swick, CT, 1986)	0.58
" Safety is increased through temporary discontinuation or dosage reduction of lithium in special risk situations."	( New developments in long-term preventive therapy. Schou, M, 1986)	0.27
" The dosage of VPA was adjusted to attain the level of 100-150 micrograms/ml."	( A trial of discontinuation of barbiturates in patients with secondary generalized epilepsy. Hosokawa, K; Kugoh, T, 1986)	0.27
" Thereafter, suppositories were administered for 2-7 days and serum levels were again determined (identical dosing and sampling times)."	( Bioavailability of sodium valproate suppositories during repeated administration at steady state in epileptic children. Bourgeois, BF; Issakainen, J, 1987)	0.27
" The dosage was 900 mg per day, administered orally."	( [Preventive effect of dipropylacetamide in bipolar manic-depressive psychoses]. Kabes, J; Peterová, E; Vencovský, E, 1987)	0.27
" At a mean daily dosage of less than 20 mg/kg, 83% of the patients became seizure-free."	( Monotherapy with valproate in primary generalized epilepsies. Beaumanoir, A; Blajev, B; Bourgeois, B; de la Cruz, N; Despland, PA; Egli, M; Geudelin, B; Kaspar, U; Ketz, E; Kronauer, C, 1987)	0.27
" It was found that both the dosage and timing of VPA administration were crucial in the development of lesions which are similar to human spina bifida aperta."	( New animal model for the study of neural tube defects. McCollough, D; Michejda, M, 1987)	0.27
") dosage form of valproic acid (VPA), ointments containing VPA and both VPA and its calcium salt (VPA-Ca) were prepared."	( Percutaneous absorption of valproic acid and its plasma concentration after application of ointment. Ito, Y; Iwaki, M; Ogiso, T; Yamahata, T; Yamamoto, Y, 1987)	0.91
" We founded a good relationship between PRI dosage and PB plasma levels."	( [Usefulness of the evaluation of plasma levels of primidone and phenobarbital]. Franzoni, E; Govoni, M; Mambelli, M; Masoni, P, )	0.13
" Dosage should be reduced when valpromide is used in combination with these drugs."	( [Use of valpromide in psychiatric therapeutics]. Lambert, PA; Venaud, G, )	0.13
" It was concluded that Cmax with a film-coated tablet of VPA can be detected if blood is taken at around 3 hours after the dosage under nonfasting conditions."	( Bioavailability of a film-coated tablet of valproate in nonfasting volunteers. Awaya, A; Furuyama, M; Horie, M; Ishikawa, T; Ohuchi, M; Okajima, K; Sobajima, H; Suchi, M; Wanibe, M; Yamaguchi, A, 1987)	0.27
" Two VA-filled Alzet osmotic minipumps were implanted subcutaneously on gestation day 5 for continuous exposure of a total daily dosage of 850 mg/kg on gestation days 5-12."	( Effects of sodium valproate and oxygen on the CD-1 mouse fetus. Hayes, TG; Kernan, B; Oca, M; Paulson, RB; Sachs, LA; Sucheston, ME; Weiss, HS; Weiss, S, 1988)	0.27
"3 years) during a dosage interval at steady state."	( Pharmacokinetics of free and total sodium valproate in adolescents and young adults during maintenance therapy. Herngren, L; Nergårdh, A, 1988)	0.27
" Children can begin to receive valproate treatment in a dosage of 20 to 30 mg/kg per day in two or three divided doses."	( Valproate monotherapy in children. Murphy, JV, 1988)	0.27
" In response to the effects of enzyme induction, valproate dosage may need to be doubled to maintain therapeutic serum levels."	( Pharmacologic interactions between valproate and other drugs. Bourgeois, BF, 1988)	0.27
" In three patients who were investigated after co-medications were eliminated, clearances and dosage requirements decreased by more than 50%."	( Valproic acid pharmacokinetics in children: III. Very high dosage requirements. Cloyd, JC; Fischer, JH; Fraser, GL; Green, KH; Kriel, RL, )	1.57
" In each patient, the average unbound fraction for a dosing interval increased with increase in sodium valproate dose."	( Changes in clearance of sodium valproate with changes in dose. Bury, RW; Fullinfaw, RO; Kilpatrick, CJ; Moulds, RF, 1987)	0.27
" In determining the dose and dosing interval of VPA, consider a possible alteration in the pharmacokinetics relating to age and other concurrent AED therapy."	( Comparison of steady-state pharmacokinetics of valproic acid in children between monotherapy and multiple antiepileptic drug treatment. Chiba, K; Hori, M; Iriki, T; Ishizaki, T; Naitoh, H; Shirai, Y; Suganuma, T, 1985)	0.53
" The PTZ infusion model was tested in a preliminary dose-response study of the anticonvulsant valproic acid (VPA)."	( A timed intravenous pentylenetetrazol infusion seizure model for quantitating the anticonvulsant effect of valproic acid in the rat. Pollack, GM; Shen, DD, 1985)	0.7
" If necessary the dosage has to be reduced or medication stopped."	( [Acute liver necrosis caused by valproate]. Hackenberg, K; Rengeling, M; Rühl, G; Zäh, W, 1985)	0.27
" The relation between the ethosuximide dosage given and the plasma concentration level was good."	( Evaluation of treatment in typical absence seizures. The roles of long-term EEG monitoring and ethosuximide. Blomquist, HK; Zetterlund, B, 1985)	0.27
" On the fifth day, blood samples were drawn over each dosage interval."	( Valproic acid clearance: unbound fraction and diurnal variation in young and elderly adults. Bauer, LA; Davis, R; Levy, RH; Raisys, V; Wilensky, A, 1985)	1.71
" These include patient age, concurrent anticonvulsant therapy, and dosage of VPA."	( A multivariable analysis of factors governing the steady-state pharmacokinetics of valproic acid in 52 young epileptics. Hall, K; Irvine-Meek, J; Johnston, B; Leroux, M; Otten, N; Seshia, S, )	0.36
" The incidence of malformations was greater at the higher dosage levels of 340 mg/kg and 560 mg/kg, with a predominance of exencephaly, open eyelids, and gross skeletal defects."	( Teratogenic effects of valproate in the CD-1 mouse fetus. Hayes, TG; Paulson, GW; Paulson, RB; Sucheston, ME, 1985)	0.27
" After discontinuation of enzyme-inducing AEDs, serum VPA concentrations can be maintained with a lower VPA dosage given less frequently."	( Valproic acid pharmacokinetics in children. II. Discontinuation of concomitant antiepileptic drug therapy. Cloyd, JC; Fischer, JH; Kriel, RL, 1985)	1.71
"Five new sustained-release dosage forms of valproic acid (VPA) were developed."	( Pharmacokinetic evaluation of novel sustained-release dosage forms of valproic acid in humans. Abramsky, O; Bialer, M; Dubrovsky, J; Friedman, M; Raz, I, )	0.63
" Acute intraperitoneal administration of the other drugs revealed VPA to be an effective anticonvulsant agent, whereas ethosuximide and diazepam were ineffective at dosage levels that are normally effective in mice as determined by classical testing methods such as electroshock and chemoshock."	( Seizure control following administration of anticonvulsant drugs in the quaking mouse. Abbott, LC; Bennett, GD; Finnell, RH; Taylor, SM, 1985)	0.27
" The dose-response curve of the effects has a shape similar to that for ethanol."	( Excitable channel currents and gating times in the presence of anticonvulsants ethosuximide and valproate. Adelman, WJ; Brennan, JJ; Fohlmeister, JF, 1984)	0.27
"From the analysis of 115 cases of primary generalized epilepsies treated for a mean duration of 43 months with sodium valproate as sole therapy, it appears that: the mean effective daily dosage is 21 mg/kg; the efficacy of valproate proved excellent in 82."	( [Monotherapy with sodium valproate in generalized primary epilepsy. 2d phase: Study of long-term efficacy and tolerance]. Feuerstein, J; Revol, M; Roger, J; Sallou, C; Truelle, JL; Vercelletto, P; Weber, M, 1983)	0.27
" The dose-response curve for naloxone against seizure activity induced by leucine enkephalin was the same as that in gamma-hydroxybutyrate-induced petit mal."	( Anticonvulsants specific for petit mal antagonize epileptogenic effect of leucine enkephalin. Bearden, LJ; Snead, OC, 1980)	0.26
"Eighteen infants with infantile spasms were given sodium dipropylacetate at a dosage of 20mg/kg/day."	( Treatment of infantile spasms with sodium dipropylacetic acid. Incorpora, G; La Rosa, M; Li Volti, S; Mollica, F; Pavone, L, 1981)	0.26
" After chronic dosing the sedative effects of flunitrazepam showed tolerance and the increases in exploration remained while locomotion was less increased."	( Effects of agents which enhance GABA-mediated neurotransmission on licking conflict in rats and exploration in mice. Gardner, CR; Piper, DC, 1982)	0.26
"Pharmacokinetics as the basis for dosage calculation for acute and subacute treatment of status epilepticus have been discussed."	( Clinical pharmacokinetics of drugs used in the treatment of status epilepticus. Baars, AM; van der Dries, A; van der Kleijn, E; Vree, TB, 1983)	0.27
" Food consumption and body weight gain were significantly reduced during the dosing period with both salts at dose levels of 600 mg/kg."	( Teratogenesis of calcium valproate in rats. de la Iglesia, FA; Fitzgerald, JE; Humphrey, RR; Jordan, H; Ong, LL; Petrere, JA; Sakowski, R; Schardein, JL, )	0.13
"Equivalent doses of enteric-coated divalproex were substituted for valproic acid in 15 epileptic patients who were on a three- or four-times-a-day dosing schedule."	( Twice-daily dosing of valproate with divalproex. Hammond, EJ; Karas, BJ; Perchalski, RJ; Wilder, BJ, 1983)	0.5
" This difference was most pronounced in patients with valproic acid dosage increases in excess of 20% and no change in their concurrent anticonvulsant therapy between the single-dose and steady-state study periods."	( First-dose and steady-state pharmacokinetics of valproic acid in children with seizures. Budnick, D; Hall, K; Irvine-Meek, J; Leroux, M; Otten, N; Seshia, SS; Verma, M, )	0.64
"5 microgram/ml and provides the capability of conducting absolute bioavailability and pulsed dosing studies with deuterated drug analogues without a mass spectrometer."	( Resolution of valproic acid from deuterated analogues and their quantitation in plasma using capillary gas chromatography. Hoffman, DJ; Porter, WR, 1983)	0.63
"A new sustained release dosage form of valproic acid (VPA) was developed."	( Comparative pharmacokinetic analysis of a novel sustained release dosage form of valproic acid in dogs. Bialer, M; Dubrovsky, J; Friedman, M, )	0.63
" When binding is altered, the total concentration no longer reflects the amount of pharmacologically active drug in the plasma: this may mislead the clinician into making inappropriate dosage adjustments."	( Free level monitoring of antiepileptic drugs. Clinical usefulness and case studies. Perucca, E, 1984)	0.27
" Total average steady-state concentration (Css) during the morning dosage interval was 50."	( Diurnal variation in valproic acid clearance. Bauer, LA; Davis, R; Levy, RH; Raisys, V; Wilensky, A, 1984)	0.59
" They were subsequently followed up as outpatients, and Phenobarbital and sodium valproate levels were measured regularly to ascertain compliance with the treatment and to adjust the dosage accordingly."	( Prevention of recurrent febrile convulsions--a randomized therapeutic assay: sodium valproate, phenobarbital and placebo. Gilly, R; Mamelle, JC; Mamelle, N; Plasse, JC; Revol, M, 1984)	0.27
" There was no statistically significant difference between the 2 dosage schedules, and the simplicity of monodose treatment is an important factor in good patient compliance."	( Monodose versus 3 daily doses of sodium valproate: a controlled trial. Alving, J; Arentsen, J; Gjerløff, I; Secher, BG, 1984)	0.27
" In the dosage used, l-tryptophan was tolerated well by these children, and seizure frequency, as a whole, remained unaltered."	( l-Tryptophan in hyperactive child syndrome associated with epilepsy: a controlled study. Ghose, K, 1983)	0.27
" In 8 of them, a therapeutic dosage of VPA caused modifications of the state of consciousness ranging from coma to drowsiness and stupor."	( Hyperammonemia and valproate-induced alterations of the state of consciousness. A report of 8 cases. Arnetoli, G; Campostrini, R; Moroni, F; Paganini, M; Zaccara, G; Zappoli, R, 1984)	0.27
" Conversely, anticonvulsants may influence the dosage requirements of oral anticoagulants by inducing their metabolism."	( Interactions between anticonvulsants and other commonly prescribed drugs. Kutt, H, 1984)	0.27
" Multiple metabolic pathways, including dehydrogenation, isomerization, hydration, hydroxylation, reduction and epoxidation were inferred from the metabolites obtained after dosage of the unsaturated metabolites."	( Aspects of the metabolism of valproic acid. Granneman, GR; Kesterson, JW; Machinist, JM; Wang, SI, 1984)	0.56
" There were no significant differences between weight gainers and weight-stable patients with regard to age, sex, pretreatment overweight, duration of treatment, dosage or serum levels of valproate."	( Weight gain during treatment with valproate. Andersen, T; Dam, M; Dinesen, H; Gram, L, 1984)	0.27
" Significant positive correlations were found between the dosage of CBZ, DPH, PMD and PB and both indices of enzyme induction."	( A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients. Hedges, A; Makki, KA; Perucca, E; Richens, A; Ruprah, M; Wilson, JF, 1984)	0.27
" The drug did, however, induce hepatic lipid accumulation in mature rats and in young rats dosed concomitantly with phenobarbital."	( The hepatotoxicity of valproic acid and its metabolites in rats. I. Toxicologic, biochemical and histopathologic studies. Granneman, GR; Kesterson, JW; Machinist, JM, )	0.45
"The objective of this investigation was to study the teratogenic effects of dosage levels and time of administration of three anticonvulsant drugs (carbamazepine [CMZ], sodium valproate [NaV], and diphenylhydantoin [DPH]) on craniofacial development in the CD-1 mouse fetus."	( Teratogenic effects of dosage levels and time of administration of carbamazepine, sodium valproate, and diphenylhydantoin on craniofacial development in the CD-1 mouse fetus. Eluma, FO; Hayes, TG; Paulson, RB; Sucheston, ME, 1984)	0.27
" Dosage was adjusted up to a maximum of 1500 mg sodium valproate per day."	( The role of sodium valproate as an anti-manic agent. Prasad, AJ, 1984)	0.27
" The patients' therapies were initiated with the prescribed doses of valproic acid and then maintained on fixed doses and dosing intervals until steady-state trough serum samples were obtained."	( Single-dose model for predicting steady-state valproic acid serum concentrations in seizure patients. Garnett, WR; Pellock, JM; Poynor, WJ; Pugh, CB, )	0.62
" 4-hydroxybenzaldehyde, a potent SSADH inhibitor did not increase GABA level at a dosage which induces a 99% inhibition of SSADH."	( [Mechanism of action of an anticonvulsant, sodium dipropylacetate]. Ciesielski, L; Gobaille, S; Klein, M; Mandel, P; Simler, S, 1981)	0.26
" Clearance, volume of distribution and half-life values obtained after intravenous dosing were comparable to literature values."	( Meal-dependent absorption of enteric-coated sodium valproate. Akbaraly, R; Brachet-Liermain, A; Cenraud, B; Gomeni, R; Guyot, M; Levy, RH; Loiseau, P; Morselli, PL, 1980)	0.26
" The dosage was phenobarbitone 3-6 mg/kg per day; sodium valproate 30-60 mg/kg per day."	( Continuous sodium valproate or phenobarbitone in the prevention of 'simple' febrile convulsions. Comparison by a double-blind trial. Bower, B; Ngwane, E, 1980)	0.26
" Eight consecutive oral doses were taken at 12-hr intervals at each dosing level."	( Valproic acid dosage and plasma protein binding and clearance. Bowdle, AT; Levy, RH; Patel, IH; Wilensky, AJ, 1980)	1.7
" However, no adjustment of phenytoin dosage is warranted, unless clinically indicated, since the free phenytoin levels remain unchanged."	( Interaction between phenytoin and valproate. Beran, RC; Sansom, LN; Schapel, GJ, 1980)	0.26
"The incidence of malformations in fetal mice exposed to phenytoin depends on drug dosage and the strain of mice."	( Teratogenic effects of anticonvulsants. Paulson, GW; Paulson, RB, 1981)	0.26
"The authors describe a method of dosage of valproic acid by gas chromatography."	( [Dosage of the pentanoic, propyl 2 acid (valproic acid). Utilization of esters of heavy alcohols (author's transl)]. Alix, D; Bergot, A; Berthou, F; Curunet, M; Picart, D; Riche, C, 1981)	0.79
" Sodium valproate depresses phenytoin protein binding and so invalidates plasma phenytoin monitoring as a means of determining precise phenytoin dosage requirements."	( Phenytoin-valproate interaction: importance of saliva monitoring in epilepsy. Hamshaw-Thomas, A; Knott, C; Reynolds, F, 1982)	0.26
" The signs and symptoms did not directly correlate with VPA dosage and the arterial ammonium levels did not correlate with serum VPA concentrations."	( Sodium valproate-induced hyperammonemia without clinical hepatic dysfunction. Beckner, RR; Marini, AM; Passarelli, C; Wagle, W; Zaret, BS, 1982)	0.26
" These side-effects are dose-related, and the daily dosage should never exceed 40 mg/kg."	( [Sodium valproate, platelet dysfunction and bleeding (author's transl)]. Loiseau, P, 1981)	0.26
" A comparison of the mean steady-state plasma levels during a dosing interval and the areas under these curves showed no differences in these parameters."	( Bioavailability of a slow-release preparation of valproic acid under steady-state conditions. Klotz, U, 1982)	0.52
" Dosage of sodium valproate was increased to 800 mg/day in the first week and to 1 g/day in the second week of treatment."	( Sodium valproate and cognitive functioning in normal volunteers. Thompson, PJ; Trimble, MR, 1981)	0.26
" However, the effect on seizure threshold could not be enhanced by an increase in the daily dosage of the GABA-T inhibitors and, especially with higher doses, tolerance to the anticonvulsant effect developed."	( Anticonvulsant and biochemical effects of inhibitors of GABA aminotransferase and valproic acid during subchronic treatment in mice. Löscher, W, 1982)	0.49
"In view of the observed variation of valproic acid (VPA) free fraction (fp) during a dosing interval and the competitive binding effect of free fatty acids (FFA) in vitro, this study was designed to address the existence of diurnal variations in the fp of VPA."	( Diurnal oscillations in plasma protein binding of valproic acid. Levy, RH; Ojemann, LM; Patel, IH; Venkataramanan, R; Viswanathan, CT, 1982)	0.79
" Fortunately, the drugs used by the majority of these patients are readily measured in plasma, and in most cases the plasma concentration is a valid measure of the appropriateness of the dosage of drug administered."	( Antiepileptic therapeutic drug monitoring. Cohan, SL, 1981)	0.26
" New antiepileptic drugs have improved medical management, and technical and theoretical advances in pharmacokinetics have permitted physicians to design balanced dosing for individual patients."	( Recent developments in the diagnosis and therapy of epilepsy. Crandall, PH; Engel, J; Sterman, MB; Troupin, AS; Wasterlain, CG, 1982)	0.26
"1 The fluctuations in protein binding of sodium valproate during one dosing interval were studied in five patients stabilized on valproate and taking concurrent anticonvulsant therapy."	( Intra-dose variation in plasma protein binding of sodium valproate in epileptic patients. Kilpatrick, CJ; Marty, JJ; Moulds, RF, 1982)	0.26
" A significant inverse relationship was found between plasma carnitine concentrations and the dosage of valproic acid, and between plasma carnitine and blood ammonia values."	( Carnitine deficiency and hyperammonemia associated with valproic acid therapy. Endo, F; Matsuda, I; Ohtani, Y, 1982)	0.72
" A cross-sectional analysis of items such as designs, patient sampling principles, recording of effect parameters and side effects, concomitant treatments, and statistical evaluations demonstrated that cross-over designs, investigating fixed dosage schedules, were extensively used."	( Controlled trials in epilepsy: a review. Bentsen, KD; Flachs, H; Gram, L; Parnas, J, 1982)	0.26
"The authors studied antipyrine disposition before and after delivery in 4 epileptic women whose anticonvulsant plasma level per dosage ratio was lowered during pregnancy, and compared the results to those found in nonpregnant women undergoing antiepileptic treatment (N = 6) and healthy women (N = 6)."	( Antipyrine disposition in relation to lowered anticonvulsant plasma level during pregnancy. Chiba, K; Ishizaki, T; Nakazawa, Y; Tabuchi, T; Wagatsuma, T, 1982)	0.26
" 14 blood samples were taken during a 12-h dosing interval at steady state while in a fed condition and also during a 27 h fast."	( The influence of free fatty acids on valproic acid plasma protein binding during fasting in normal humans. Bowdle, TA; Levy, RH; Patel, IH; Wilensky, AJ, 1982)	0.54
" However, displacement alone, unlike induced metabolism, should not affect the drug's dose-response relationship."	( Drug interactions with valproic acid. Koch, KM; Levy, RH, 1982)	0.57
" VPA (as the sodium salt) was administered in a dosage of 170-180 mg/kg/day divided into three equal doses in the form of enteric-coated tablets."	( Plasma levels of valproic acid and its metabolites during continued treatment in dogs. Löscher, W, 1981)	0.6
" The therapeutic effect appears to correlate better with dosage per kilogram body weight than with the actual plasma concentrations."	( Therapeutic monitoring of valproic acid. Schobben, F; van der Kleijn, E; Vree, TB, 1980)	0.56
" Therefore, coadministered drugs which are highly protein bound or hepatically metabolised may require dosage adjustment."	( Valproic acid. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy. Davis, R; McTavish, D; Peters, DH, 1994)	1.73
" Male Sprague-Dawley rats (150-180 g, 4 rats per group) were dosed ip with 4-ene VPA (0."	( Fluorinated analogues as mechanistic probes in valproic acid hepatotoxicity: hepatic microvesicular steatosis and glutathione status. Abbott, FS; Borel, AG; Fujimiya, T; Tang, W, )	0.39
" The median dosage of valproate was 375 mg infused over 1 hour."	( Safety of intravenous valproate. Dean, C; Devinsky, O; Gates, J; Leppik, I; Pellock, JM; Ramsay, RE; Willmore, LJ, 1995)	0.29
" CBZ dosage was decreased, with prompt resolution of symptoms."	( Oculogyric crisis induced by carbamazepine. Barkley, GL; Gorman, M, 1995)	0.29
"Timing of dosing is important for VA kinetics and feeding schedule is one of synchronizers in VA kinetics."	( Chronopharmacokinetics of valproic acid following constant-rate administration in mice and influence of feeding schedule. Ogawa, N; Ohdo, S; Song, JG, 1995)	0.59
"We report a fatal case of haemorrhagic pancreatic necrosis in a 15-year-old mentally retarded epileptic male who had been taking sodium valproate (VPA) in the recommended dosage for one and a half years."	( [Fatal pancreatitis associated with valproate therapy]. Engelmann, MD; Henriksen, SD; Tingsgaard, LK, 1995)	0.29
" The most frequently used dosage was 40 IU per day, and the most frequent duration of treatment was 1 to 2 months."	( The treatment of infantile spasms by child neurologists. Bobele, GB; Bodensteiner, JB, 1994)	0.29
" Neuroleptic dosing of manic patients is probably too high and exposes patients to an unnecessary risk of side effects including tardive dyskinesia."	( Treatment approaches for acute mania. Chou, JC; Sweeney, EA; Tuma, I, 1993)	0.29
"Data from published research were extracted and evaluated according to study design, sample size, dosing regimen, outcome measures, and treatment efficacy and safety."	( Treatment of infantile spasms. Casto, DT; Haines, ST, 1994)	0.29
" An understanding of the underlying pharmacokinetic processes, including the need of most elderly patients for lower doses and longer dosing intervals, permits more effective management of therapy and reduces the risk for adverse reactions."	( Antiepileptics in the elderly. Pharmacoepidemiology and pharmacokinetics. Cloyd, JC; Lackner, TE; Leppik, IE, 1994)	0.29
" Between-regimen steady-state comparisons of pharmacokinetic parameters revealed some significant differences in mean time to Cmax (Tmax), Cmax, Cmin, AUC, and total body clearance for respective day-4 dosing intervals, but not for the entire day 4, except for Cmin and Tmax."	( Pharmacokinetics of valproate after multiple-dose oral and intravenous infusion administration: gastrointestinal-related diurnal variation. Cavanaugh, JH; Granneman, GR; Hussein, Z; Lamm, J; Mukherjee, D, 1994)	0.29
" The more common dose-related phenomena quite specific to VPA included weight gain, tremor and hair loss and did not usually abate with continued treatment but may respond to a lowering of the dosage or to a change in the dosing regimen."	( [Tolerance to and unwanted effects of valproate sodium]. Despland, PA, 1994)	0.29
" All these patients were receiving the usual dosage (1000 to 1500 mg per day) of Valproic acid (VPA)."	( Impairment of consciousness induced by valproate treatment following neurosurgical operation. Baulac, M; de Billy, A; Durand, G; Landau, J; Philippon, J, 1993)	0.51
" An appropriate dosing regimen (consecutive doses of VPA on Day 9 of gestation) can also result in a low incidence of spina bifida aperta and a high incidence of spina bifida occulta in the mouse."	( Valproic acid-induced neural tube defects. Nau, H, 1994)	1.73
" Recommendations are made for a higher initial dosage regime for sodium valproate in partial seizures."	( A multicentre comparative trial of sodium valproate and carbamazepine in adult onset epilepsy. Adult EPITEG Collaborative Group. Cartlidge, NE; Davidson, DL; Easter, DJ; Richens, A, 1994)	0.29
"A retrospective study of 113 patients treated with a sustained-release form of valproate (SRF-VPA), known as the "chrono" formulation in most European countries, led to the following conclusions: Patients treated with the old VPA formulation could immediately receive the same daily dosage of SRF-VPA without loss of seizure control when administered as a single evening dose."	( A retrospective study of 113 epileptic patients treated with sustained-release valproate. Despland, PA, 1994)	0.29
"This pharmaco-epidemiologic study was undertaken to determine if the combination of clozapine and valproate poses an increased risk of blood dyscrasias, liver function abnormalities, or other side effects and to develop dosing guidelines when the combination is utilized."	( Concurrent use of clozapine and valproate in affective and psychotic disorders. Castillo, J; Centorrino, F; Kando, JC; Tohen, M, 1994)	0.29
" No dosage adjustment is necessary when GBP and CBZ or VPA are coadministered."	( Lack of interaction of gabapentin with carbamazepine or valproate. Bockbrader, HN; Chang, T; Erdman, GR; Leppik, IE; Posvar, EL; Radulovic, LL; Sedman, AJ; Uthman, BM; Wilder, BJ, )	0.13
" The patient was treated with high dosage prednisone with partial improvement, but continued to have exacerbations at lower dosages."	( Systemic lupus erythematosus associated with use of valproate. Asconapé, JJ; Lancman, ME; Manning, KR, )	0.13
") bolus] was administered to 8 normal volunteers before and after chronic dosing with VPA."	( Lorazepam-valproate interaction: studies in normal subjects and isolated perfused rat liver. Anderson, GD; Gidal, BE; Kantor, ED; Wilensky, AJ, )	0.13
" Median AUCs of CBZ, VPA and PHT during a dosage interval did not differ significantly after treatment with OXC and placebo."	( A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients. Blacklaw, J; Brodie, MJ; Connelly, D; Forrest, G; Gillham, RA; McKee, PJ; Walker, SM, 1994)	0.29
" For 12 patients, treatment could be reduced to monotherapy, but for those with valproate (VPA) comedication LTG dosage had to be increased; 25% of patients with VPA monotherapy exhibited skin rash, appearing 3-18 days after starting LTG."	( Lamotrigine in treatment of 120 children with epilepsy. Chavez, F; Dulac, O; Pajot, N; Palacios, L; Rey, E; Schlumberger, E, )	0.13
" We collected dosage interval urine samples from three groups of 10 valproate patients: (1) valproate monotherapy, (2) valproate with carbamazepine, and (3) valproate with phenytoin."	( Interaction between valproate and branched-chain amino acid metabolism. Acheampong, AA; Anderson, GD; Levy, RH, 1994)	0.29
" Regarding the controlled-release characteristics of the test formulation, fluctuation index and percentage fluctuation of the twice a day dosage regimen of the test formulation were comparable with those of the thrice a day dosage regimen of the conventional tablet."	( Pharmacokinetic comparison of two valproic acid formulations--a plain and a controlled release enteric-coated tablets. Chong, WS; Jang, IJ; Lee, KH; Lee, N; Myung, HJ; Rha, JH; Shin, SG, 1993)	0.57
" The frequency of withdrawal symptoms was significantly related to the dose of valproate given to the mothers in the third trimester, and there was a tendency for both the frequency of the minor abnormalities and the major malformations to be related to the valproate dosage in the first trimester."	( Malformations, withdrawal manifestations, and hypoglycaemia after exposure to valproate in utero. Ebbesen, F; Thisted, E, 1993)	0.29
" A week of daily dosing with CLZ led to no accumulation of drug in brain; a week of fluoxetine pretreatment increased analyte concentrations (serum, 86%; brain, 61%), but valproate had little effect."	( Tissue concentrations of clozapine and its metabolites in the rat. Baldessarini, RJ; Centorrino, F; Cohen, BM; Flood, JG; Huston-Lyons, D; Volpicelli, SA, 1993)	0.29
" To provide further data on the safety and efficacy of valproate oral loading in the treatment of acute mania, we evaluated 13 consecutive patients with acute manic syndromes who received valproate initiated at a dosage of 20 mg/kg/day."	( Valproate as a loading treatment in acute mania. Bennett, JA; Keck, PE; McElroy, SL; Tugrul, KC, 1993)	0.29
" Both studies used an identical trial design comparing FBM with a low dosage of valproate (VPA)."	( Felbamate in the treatment of refractory partial-onset seizures. Jensen, PK, 1993)	0.29
" In the present experiments, it was studied if GABA-T activity in whole tissue and synaptosomes prepared from whole tissue of 11 brain regions of rats is affected in vivo by treatment with an anticonvulsant dosage of VPA."	( In vivo administration of valproate reduces the nerve terminal (synaptosomal) activity of GABA aminotransferase in discrete brain areas of rats. Löscher, W, 1993)	0.29
" A drug delivery system (DDS) enabling a constant-rate administration is attractive from the clinical point of view, namely, such a system could minimize the peak and trough variation in plasma drug concentration after dosing so as to avoid toxicity associated with drug levels exceeding the upper limit of therapeutic range and lack of effect with drug levels dropping below the lower limit of the range."	( [Chronopharmacology and DDS (drug delivery system)]. Ogawa, N; Ohdo, S, 1993)	0.29
"The aim of the study was to characterize, from the relationship between total and free serum levels of valproic acid obtained over a broad dosage range (10-50 mg/kg), the parameters defining the in-vivo kinetic behaviour of the binding of valproic acid to plasma proteins, their pharmacokinetic and clinical repercussions, and their application to therapeutic drug monitoring (TDM)."	( Plasma protein binding kinetics of valproic acid over a broad dosage range: therapeutic implications. Alonso González, AC; Domínguez-Gil, A; García Sánchez, MJ; Gómez Bellver, MJ; Santos Buelga, D, 1993)	0.78
" Three months before admission, this dosage was increased to 300 mg/d and phenobarbital (PB) 100 mg/d was added because the seizures were incompletely controlled."	( Valproate-induced coma: case report and literature review. Clavería, LE; Coria, F; Duarte, J; Fernandez, E; Macias, S, 1993)	0.29
" The neurologic symptoms resolved upon VPA dosage reduction."	( Apparent valproic acid neurotoxicity in a hypoalbuminemic patient. Beinlich, BR; Collins, DM; Gidal, BE, 1993)	0.7
" New medications, such as sumatriptan, and new dosage forms of older medications, including dihydroergotamine, NSAIDs, and phenothiazines are available to treat acute attacks."	( Therapeutic advances in migraine. Solomon, GD, 1993)	0.29
" The t 1/2 and AUC values of PB were significantly increased by ZNS coadministration, and a significant decrease in the Vd/F value of PHT was observed after multiple dosing of ZNS."	( Pharmacokinetic interaction of zonisamide in rats. Effect of zonisamide on other antiepileptics. Fukuchi, H; Kimura, M; Kimura, Y; Kitaura, T; Miyake, K; Tanaka, N, 1993)	0.29
" In 11 patients with early symptoms and signs of possible fatal VPA-associated hepatotoxicity, the following spectrum of benign clinical conditions was observed: unusually severe side effect during initiation of VPA therapy (1 patient), high VPA dosage (2 patients), reversible impairment of coagulation with bleeding manifestations in association with a slight increase in transaminase levels (1 child), and reversible liver dysfunction associated with febrile illness (7 patients)."	( Valproate (VPA) metabolites in various clinical conditions of probable VPA-associated hepatotoxicity. Drews, E; Nau, H; Penzien, J; Schultze, K; Seidel, U; Siemes, H; Wittfoht, W, )	0.13
" Dosage of the medication was adjusted to maintain serum valproic acid levels between 50 and 100 micrograms/mL, provided there were no significant side effects at that level."	( Valproic acid treatment of chronic daily headache. Spillane, T; Vijayan, N, 1995)	1.98
" In this pilot study 13 adult male alcoholics received one month of oral, low dose sodium valproate (15 mg/kg/d) followed by one month of placebo followed by one month of sodium valproate at the standard anticonvulsant dosage (45 mg/kg/d)."	( The use of sodium valproate in the treatment of alcoholism. Borrett, G; Duerksen, DR; German, GB; Hoeschen, L; Minuk, GY; Rockman, GE, 1995)	0.29
"The toxicity of an agent or the therapeutic effect of a drug may be assessed by a dose-response study."	( Exact power computation for dose-response studies. Hirji, KF; Tang, ML; Vollset, SE, 1995)	0.29
" Furthermore, we sought to evaluate whether a relationship existed between VPA dosage and plasma clearance for both total and unbound or free drug."	( Relationship between valproic acid dosage, plasma concentration and clearance in adult monotherapy patients with epilepsy. Gidal, BE; Maly, MM; Pitterle, ME; Spencer, NW, 1995)	0.61
"Sixty-five hospitalized patients who met the Research Diagnostic Criteria for bipolar disorder with mania were treated with divalproex, 750 mg/day for 2 days and then 1,000 mg/day on days 3-5; the dosage was subsequently adjusted as clinically indicated for the remainder of the 21-day study."	( Relation of serum valproate concentration to response in mania. Bowden, CL; Calabrese, JR; Davis, JM; Goodnick, P; Janicak, PG; Kimmel, SE; Morris, DD; Orsulak, P; Risch, SC; Rush, AJ; Small, JG; Swann, AC, 1996)	0.29
" VPA dosage was tapered and discontinued, with accompanying resolution of clinical, immunological and hematological signs of SLE 6 weeks after VPA discontinuation."	( Valproate-induced systemic lupus erythematosus in a patient with partial trisomy of chromosome 9 and epilepsy. Diomedi, M; Gigli, GL; Grazia Pomponi, M; Masala, C; Pauri, F; Placidi, F; Scalise, A; Silvestri, G, 1996)	0.29
" TPM was added to the baseline antiepileptic drug (AED) at a dosage of up to 800 mg/day, after which the baseline drug was discontinued, when possible."	( Drug interaction profile of topiramate. Bourgeois, BF, 1996)	0.29
"The influence of dosing time on embryotoxicity of valproate was investigated in ICR (Institute of Cancer Research, USA) mice under light-dark (12:12) cycle."	( Circadian rhythm of embryotoxicity induced by sodium valproate in mice. Ogawa, N; Ohdo, S; Sugiyama, T; Watanabe, H; Yoshiyama, Y, 1995)	0.29
" The mean area under the curve for the sum of amitriptyline and nortriptyline concentrations was 42% higher with concomitant divalproex dosing than it was for dosing with amitriptyline alone."	( Effects of divalproex sodium on amitriptyline and nortriptyline pharmacokinetics. Awni, WM; Cavanaugh, J; Granneman, GR; Shi, H; Wong, SL, 1996)	0.29
" In this study, we compared the extent and pattern of covalent adduct formation in plasma and livers of rats dosed with the nonsteroidal anti-inflammatory drugs (NSAIDs) zomepirac (ZP) and diflunisal (DF), the hypolipidemic agent clofibric acid (CA), and the anti-epileptic agent valproic acid (VPA)."	( Chemical and immunochemical comparison of protein adduct formation of four carboxylate drugs in rat liver and plasma. Bailey, MJ; Dickinson, RG, )	0.31
" Compliance and adequacy of dosing were assessed by pill counts and monthly blood levels."	( A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors. Akerley, W; Choy, H; Cole, BF; Friedberg, MH; Furie, K; Glantz, MJ; Lathi, E; Lekos, A; Louis, S; Wahlberg, L, 1996)	0.29
" Bile samples collected from male Sprague-Dawley rats dosed intraperitoneally with 4-ene VPA or its [2H7]-analogue (100 mg kg-1) were injected on to an ODS column interfaced to a LC/MS/MS instrument using electrospray ionization."	( Characterization of thiol-conjugated metabolites of 2-propylpent-4-enoic acid (4-ene VPA), a toxic metabolite of valproic acid, by electrospray tandem mass spectrometry. Abbott, FS; Tang, W, 1996)	0.5
" The daily dosage of each drug was held constant during treatment of the obesity."	( Clearance of phenytoin and valproic acid is affected by a small body weight reduction in an epileptic obese patient: a case study. Ashikari, Y; Chiba, S; Kodama, Y; Kuranari, M; Sakata, T; Takeyama, M, 1996)	0.59
"To evaluate the steady-state pharmacokinetics of lamotrigine and valproate at three dosing levels of lamotrigine in normal volunteers receiving steady-state therapeutic doses of valproate."	( Bidirectional interaction of valproate and lamotrigine in healthy subjects. Anderson, GD; Dren, AT; Gidal, BE; Harris, SJ; Lai, AA; Levy, RH; Wargin, WA; Wolf, KB; Yau, MK, 1996)	0.29
" Each subject subsequently received three oral dosage regimens of lamotrigine (50, 100, or 150 mg/day) for 1 week each, with a 2-week washout period between lamotrigine treatment periods."	( Bidirectional interaction of valproate and lamotrigine in healthy subjects. Anderson, GD; Dren, AT; Gidal, BE; Harris, SJ; Lai, AA; Levy, RH; Wargin, WA; Wolf, KB; Yau, MK, 1996)	0.29
"As a consequence of the interaction between lamotrigine and sodium valproate, a dosage reduction of lamotrigine should be considered in patients taking a combination of valproate and lamotrigine."	( Bidirectional interaction of valproate and lamotrigine in healthy subjects. Anderson, GD; Dren, AT; Gidal, BE; Harris, SJ; Lai, AA; Levy, RH; Wargin, WA; Wolf, KB; Yau, MK, 1996)	0.29
" The usual starting dosage is 250 mg bid, titrating to 1000 mg/d if necessary."	( Valproic acid: a migraine prophylaxis alternative. Connelly, JF; Shelton, CE, )	1.57
" A patient was only considered twice if his comedication or OCBZ dosage had been changed."	( Fluctuations of 10-hydroxy-carbazepine during the day in epileptic patients. May, TW; Rambeck, B; Sälke-Kellermann, A, 1996)	0.29
" Bile samples collected from male Sprague-Dawley rats dosed ip with (E)-2,4-diene VPA (100 mg/kg) were analyzed by LC/MS/MS."	( Bioactivation of a toxic metabolite of valproic acid, (E)-2-propyl-2,4-pentadienoic acid, via glucuronidation. LC/MS/MS characterization of the GSH-glucuronide diconjugates. Abbott, FS; Tang, W, 1996)	0.56
" This study also indicates that once-daily treatment with Epilim controlled release would be a suitable replacement for twice-daily dosing with either formulation."	( Epilim chrono: a multidose, crossover comparison of two formulations of valproate in healthy volunteers. Easter, D; O'Bryan-Tear, G; Roberts, D, 1996)	0.29
" All patients received a drug dosage to ensure adequate plasma concentration and satisfactory seizure control."	( The effect of chronic carbamazepine, valproic acid and phenytoin medication on the periodontal condition of epileptic children and adolescents. Borowicz-Andrzejewska, E; Borysewicz-Lewicka, M; Galas-Zgorzalewicz, B; Zgorzalewicz, M, )	0.4
"The influence of dosing time on the embryotoxicity of sodium valproate (valproic acid, VPA) was investigated in ICR mice under a light-dark (12:12) cycle."	( Chronotoxicity of sodium valproate in pregnant mouse and embryo. Ogawa, N; Ohdo, S; Sugiyama, T; Watanabe, H; Yoshiyama, Y, 1996)	0.53
" Based on a dose-response study, the concentrations of compounds causing 50%, inhibition (IC50) of formation of thick and thin fibers were determined."	( Prediction of teratogenic potency of valproate analogues using cerebellar aggregation cultures. Berezin, V; Bock, E; Ellerbeck, U; Maar, TE; Nau, H; Schousboe, A, 1997)	0.3
" As compared to placebo, VAL, at the dosage of both 400 and 800 mg, significantly suppressed nocturnal blood melatonin levels, the higher dose being slightly more effective than the lower one."	( Suppression of nocturnal plasma melatonin levels by evening administration of sodium valproate in healthy humans. Borriello, R; Cassandro, P; Maj, M; Monteleone, P; Natale, M; Tortorella, A, 1997)	0.3
" Irrespective of the drug used, optimal clinical management requires individualization of dosage and dosing schedules based on careful evaluation of clinical response and sound knowledge of the pharmacokinetics and interaction potential of the individual compounds."	( Established antiepileptic drugs. Perucca, E, 1996)	0.29
" TPM plasma peak concentration (C(max)) and area under the concentration-versus-time curve during a 12-h dosing interval (AUC(0-12)) were slightly higher (17%; n = 8) during TPM monotherapy than during concomitant VPA therapy."	( Comparison of the steady-state pharmacokinetics of topiramate and valproate in patients with epilepsy during monotherapy and concomitant therapy. Anderson, G; Kramer, LD; Levy, RH; Liao, S; Nayak, RK; Palmer, M; Rosenfeld, WE, 1997)	0.3
" Serum concentrations of clobazam increased with dosage and age, and decreased with phenobarbital cotherapy."	( Interactions of clobazam with conventional antiepileptics in children. Cortez, M; Daneman, R; Hwang, P; Koren, G; Menzano, E; Sherwin, AL; Theis, JG, 1997)	0.3
"In this preliminary report from a placebo-controlled, double-blind, dose-response study on the use of pergolide mesylate for cocaine dependence in outpatients 8 out of 235 subjects noted adverse events requiring breaking of the blind."	( Pergolide mesylate. Adverse events occurring in the treatment of cocaine dependence. Cochrane, CE; Kajdasz, DK; Malcolm, R; Moore, JW, 1997)	0.3
" Generalized tonic-clonic seizures observed in EP mice were inhibited by valproate, administered 1 h prior to testing, in a dose-response fashion."	( Effects of valproate on amino acid and monoamine concentrations in striatum of audiogenic seizure-prone Balb/c mice. Alexiuk, NA; Vriend, JP, 1996)	0.29
" The mean +/- SD continuous neuroleptic dosage for these 33 outpatients was 416 +/- 527 mg/day chlorpromazine (CPZ) equivalents."	( Chronic neuroleptic exposure in bipolar outpatients. Godleski, LS; Griffin, RA; Mazure, CM; Sernyak, MJ; Woods, SW, 1997)	0.3
" Plasma concentration profiles of VPA, remacemide, and its active desglycinyl metabolite (ARL12495XX) were determined following single (300 mg) and multiple dosing (150 or 300 mg twice daily) of remacemide hydrochloride for 14 days with a 300-mg final dose."	( Lack of pharmacokinetic interaction between remacemide hydrochloride and sodium valproate in epileptic patients. Brodie, MJ; Girvan, J; Jamieson, V; Jones, T; Leach, JP; Richens, A, 1997)	0.3
" Dosing valproate intramuscularly in humans is problematic in view of the muscle damage."	( Pharmacokinetics and muscle histopathology of intramuscular valproate. DeToledo, J; Gallo, BV; Ramsay, RE; Slater, JD; Toledo, C, 1997)	0.3
"We describe a 27-year-old woman who developed encephalopathy and cerebral edema during treatment of refractory complex partial seizures that included acute administration of valproate (VPA) at a dosage of 35 mg/kg per day."	( Valproate-associated carnitine deficiency and malignant cerebral edema in the absence of hepatic failure. Bunch, TS; Cibula, J; Gilmore, RL; Harman, E; Millington, DS; Triggs, WJ, 1997)	0.3
" Dosing was individualized according to the response of target symptoms and side effects."	( An open trial of valproate for agitation in geriatric neuropsychiatric disorders. Erb, R; Gaile, S; Porsteinsson, AP; Tariot, PN, 1997)	0.3
" Adverse events were infrequent but the occurrence of rash appeared to correlate with rapid ascension dosing and comedication with valproic acid."	( Adult experience with lamotrigine. Messenheimer, JA; Willmore, LJ, 1997)	0.5
" No significant time or dosage effect or time by treatment effect was observed for YMRS."	( Lamotrigine in rapid-cycling bipolar disorder. Calabrese, JR; Fatemi, SH; Rapport, DJ; Thuras, P, 1997)	0.3
" A minimum of one steady state trough blood sample and one dosage interval urine were collected during days 3-6 and during days 7-14 post-injury."	( Increases in metabolism of valproate and excretion of 6beta-hydroxycortisol in patients with traumatic brain injury. Adams, CA; Anderson, GD; Awan, AB; Temkin, NR; Winn, HR, 1998)	0.3
" Although patients who finished the algorithm were taking more medication, either dosage and/or drugs, somatic complaints did not increase."	( Treatment algorithm use to optimize management of symptomatic patients with a history of mania. Kraemer, HC; Rush, AJ; Suppes, T; Webb, A, 1998)	0.3
" Reduction of VPA dosage and subsequent discontinuation 4 months later resulted in disappearance of clinical symptoms with a 20-point improvement at IQ testing and recovery of previous PM score."	( Reversible pseudoatrophy of the brain and mental deterioration associated with valproate treatment. Belmonte, A; Canapicchi, R; Casalini, C; Guerrini, R; Perucca, E, 1998)	0.3
"Three patients aged 16, 19, and 65 years with a 13- to 36-year history of partial epilepsy were receiving a therapeutic dosage of carbamazepine or phenobarbital plus either clobazam (CLB) or valproate (VPA)."	( Negative myoclonic status due to antiepileptic drug tapering: report of three cases. Aguglia, U; Gambardella, A; Oliveri, RL; Quattrone, A; Russo, C; Zappia, M, 1997)	0.3
" This study suggests that L-carnitine supplementation to valproic acid therapy may potentiate valproic acid effects in the brain, even when the clinical dosage in humans is used."	( Effect of carnitine on valproic acid concentrations in serum, brain, and liver. Sakemi, K; Takada, G, 1998)	0.86
"To conduct a pilot study on the safety and tolerability of a dosage strategy for divalproex sodium beginning with 30 mg/kg/day."	( Tolerability of oral loading of divalproex sodium in the treatment of acute mania. Hirschfeld, RM; Martinez, JM; Russell, JM, 1998)	0.3
"A divalproex dosage strategy beginning with 30 mg/kg/day for 2 days, followed by 20 mg/kg/day thereafter, was reasonably well tolerated in this group of acutely manic patients, even with the concurrent use of other psychotropic medications."	( Tolerability of oral loading of divalproex sodium in the treatment of acute mania. Hirschfeld, RM; Martinez, JM; Russell, JM, 1998)	0.3
" For comparison of drug potencies, doses increasing seizure thresholds by 20 or 50% were calculated from dose-response curves."	( Anticonvulsant drug effects in the direct cortical ramp-stimulation model in rats: comparison with conventional seizure models. Krupp, E; Löscher, W, 1998)	0.3
" Adverse effects include sedation, dyspepsia and headache early in treatment, and sexual dysfunction and increased anxiety, but these can be effectively managed with proper dosage escalation and management."	( A risk-benefit assessment of pharmacological treatments for panic disorder. Bennett, JA; Dwight, M; Keck, PE; Moioffer, M; Stanton, SP, 1998)	0.3
" Many of the adverse effects of lithium can be addressed by dosage reduction, use of sustained-release lithium, or combination therapy."	( Key treatment studies of lithium in manic-depressive illness: efficacy and side effects. Bowden, CL, 1998)	0.3
" We propose that individual dosage adjustment in VPA + CBZ polytherapy should be combined with monitoring of relevant enzyme activities in serum."	( Valproate and carbamazepine comedication changes hepatic enzyme activities in sera of epileptic children. Cepelak, I; Lenicek, J; Mandusić, A; Rekić, B; Zanić Grubisić, T, 1998)	0.3
" The median time to onset (17 days for SJS and TEN) and the median dosage at onset (50 mg vs."	( Lamotrigine-induced severe cutaneous adverse reactions. Schlienger, RG; Shapiro, LE; Shear, NH, 1998)	0.3
" The panel recommended an oral L-carnitine dosage of 100 mg/kg/day, up to a maximum of 2 g/day."	( L-carnitine supplementation in childhood epilepsy: current perspectives. Bohan, TP; Coulter, DL; De Vivo, DC; Dreifuss, FE; Greenwood, RS; Nordli, DR; Shields, WD; Stafstrom, CE; Tein, I, 1998)	0.3
" In these patients, effect of L-DOPA had become limited or increasing the dosage of L-DOPA was difficult because of its side effects."	( [Valproic acid relieved marked rigidity in three patients with end-stage parkinsonism]. Fujimoto, K; Nakano, I; Sayama, S, 1998)	1.21
"To review (retrospectively) the relationships between lamotrigine (LTG) dosage and plasma concentrations based on data generated in a routine therapeutic drug monitoring laboratory from a heterogeneous sample of patients with epilepsy."	( Lamotrigine and therapeutic drug monitoring: retrospective survey following the introduction of a routine service. Batty, AB; Black, AB; Harris, AL; Morris, RG; Sallustio, BC, 1998)	0.3
"All patient assays for LTG received over a 12 month period (339 requests from 149 patients) were reviewed and relationships between dosage and concentration calculated and grouped according to concomitant antiepileptic drug therapy."	( Lamotrigine and therapeutic drug monitoring: retrospective survey following the introduction of a routine service. Batty, AB; Black, AB; Harris, AL; Morris, RG; Sallustio, BC, 1998)	0.3
"Linear relationships were demonstrated between LTG dosage and concentration for the 3 treatment groups (LTG plus valproic acid (VPA), LTG plus enzyme inducing antiepileptic drugs, and LTG plus VPA and inducers), however, there were significant differences between groups (P<0."	( Lamotrigine and therapeutic drug monitoring: retrospective survey following the introduction of a routine service. Batty, AB; Black, AB; Harris, AL; Morris, RG; Sallustio, BC, 1998)	0.51
"Metabolic inhibition by VPA was shown to have a marked effect on LTG kinetics, suggesting either a significant LTG dosage reduction is required if plasma LTG concentrations are elevated, or alternatively, higher plasma LTG concentrations could be attained from lower dosages."	( Lamotrigine and therapeutic drug monitoring: retrospective survey following the introduction of a routine service. Batty, AB; Black, AB; Harris, AL; Morris, RG; Sallustio, BC, 1998)	0.3
" Similarly, 5 days of oral dosing with VAL (400 and 600 mg/kg) reliably reduced the intake of ethanol without affecting the intake of water."	( Valproate reduces intake of alcoholic beverage among rats. Boswell, KJ; Chambers, MD; Gardell, LR; Hubbell, CL; Reid, LD; Whalen, CA, 1998)	0.3
" Divalproex sodium was increased as tolerated using a flexible dosing schedule."	( Divalproex sodium for impulsive aggressive behavior in patients with personality disorder. Coccaro, EF; Kavoussi, RJ, 1998)	0.3
" In those patients who use these drugs at increased dosage levels or for long periods, the possibility of tubular dysfunction may be increased, and these dysfunctions may manifest in clinical symptoms."	( N-acetyl-beta-glucosaminidase and beta-galactosidase activity in children receiving antiepileptic drugs. Cenani, A; Cengiz, M; Cengiz, S; Seven, M; Yüksel, A, 1999)	0.3
"Two bioavailability studies were conducted in healthy male volunteers to determine the absorption characteristics of a new dosage form of sodium valproate consisting of sustained release pellets in a hard gelatine capsule."	( Pharmacokinetic characteristics of a new multiple unit sustained release formulation of sodium valproate. Retzow, A; Vens-Cappell, B; Wangemann, M, 1999)	0.3
" Following the pilot study the pharmacokinetics were investigated versus a conventional enteric-coated tablet after multiple dosing in 18 volunteers."	( Pharmacokinetic characteristics of a new multiple unit sustained release formulation of sodium valproate. Retzow, A; Vens-Cappell, B; Wangemann, M, 1999)	0.3
" Data obtained after multiple dose administration provided an indication of the consistency of valproate absorption from each dosage form."	( Pharmacokinetic characteristics of a new multiple unit sustained release formulation of sodium valproate. Retzow, A; Vens-Cappell, B; Wangemann, M, 1999)	0.3
"These data indicate that the new sustained release capsule possesses desirable absorption characteristics in a form that allows twice daily or even once daily dosing and therefore improves patient compliance."	( Pharmacokinetic characteristics of a new multiple unit sustained release formulation of sodium valproate. Retzow, A; Vens-Cappell, B; Wangemann, M, 1999)	0.3
" Twelve adult patients with seizures controlled by an individualized fixed dosage of valproate participated in the study."	( Lack of a clinically significant pharmacokinetic drug interaction between tiagabine and valproate. Boellner, SW; Granneman, GR; Guenther, HJ; Gustavson, LE; Sommerville, KW; Witt, GF, 1998)	0.3
" Poor compliance may contribute to the occurrence of status epilepticus, resulting in the need for substantial increases in anticonvulsant dosing to suppress seizures."	( Status epilepticus during pregnancy. A case report. Licht, EA; Sankar, R, 1999)	0.3
"A population pharmacokinetic model is proposed to estimate the individual CL for paediatric patients receiving VPA in terms of patient's dose, weight and concomitant CBZ, in order to establish a priori dosage regimens."	( Valproate population pharmacokinetics in children. Buelga, DS; Domínguez-Gil, A; García Sánchez, MJ; Otero, MJ; Serrano, BB; Serrano, J, 1999)	0.3
" Adaptive control dosing of valproate has not been fully studied in psychiatry."	( Prediction of valproate serum concentrations in adult psychiatric patients using Bayesian model estimations with NPEM2 population pharmacokinetic parameters. Lum, BL; Puentes, E; Puzantian, T, 1999)	0.3
" To provide loading and maintenance dosing for patients with hepatic induction secondary to concurrent anticonvulsants."	( Use of intravenous valproate in three pediatric patients with nonconvulsive or convulsive status epilepticus. Chicella, MF; Dalton, JT; Eades, SK; Hovinga, CA; Phelps, SJ; Rose, DF, 1999)	0.3
" The dosage of both drugs, however, may need to be reduced to minimize the risk of intolerable side effects."	( The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction. Di Perri, R; Oteri, G; Perucca, E; Pisani, F; Richens, A; Russo, MF, 1999)	0.3
" The features of the stimulant-induced seizures were distinct and included the following: (1) the duration of convulsive activity was shortest for cocaine and longest for methamphetamine, (2) only MDMA produced a secondary clonic phase after the initial ictal event, and (3) 4-methylaminorex manifested a very steep dose-response curve."	( Distinct features of seizures induced by cocaine and amphetamine analogs. Hanson, GR; Jensen, M; Johnson, M; White, HS, 1999)	0.3
" Dose-response inhibition curves determined on the control receptor and on ADNFLE-mutant receptors showed a greater sensitivity of the mutants to CBZ, with median inhibitory concentrations (IC50s) in the range of the antiepileptic plasma levels of CBZ."	( Mutated nicotinic receptors responsible for autosomal dominant nocturnal frontal lobe epilepsy are more sensitive to carbamazepine. Bertrand, D; Bertrand, S; Picard, F; Steinlein, OK, 1999)	0.3
" Significant correlations between platelet count, aggregation, and ATP release and VPA dosage and plasma concentration were also observed."	( Platelet count and function in children receiving sodium valproate. Altobelli, E; Chiarelli, F; Greco, R; Matera, V; Morgese, G; Verrotti, A, 1999)	0.3
" Valproate, when the proper therapeutic dosage was belatedly realized, was seen as a superior treatment for generalized and partial epilepsies."	( Clinical experience with new antiepileptic drugs: antiepileptic drugs in Europe. Loiseau, PJ, 1999)	0.3
" Because dosing is often modest, cost should rarely be the overriding factor in choosing a drug for a patient with newly diagnosed epilepsy in the developed world."	( Monostars: an aid to choosing an antiepileptic drug as monotherapy. Brodie, MJ, 1999)	0.3
" Seizures became diurnal and frequent, not modified by carbamazepine (CBZ) or valproate (VPA) but responding to VPA and lamotrigine (LTG) with recommended dosage schedules for this combination."	( Paradoxic reaction to lamotrigine in a child with benign focal epilepsy of childhood with centrotemporal spikes. Boyd, S; Catania, S; Cross, H; de Sousa, C, 1999)	0.3
" It also appears that rapid dosage increases for antimanic treatment can cause potentially severe side effects."	( Tiagabine appears not to be efficacious in the treatment of acute mania. Amann, B; Erfurth, A; Grunze, H; Marcuse, A; Normann, C; Walden, J, 1999)	0.3
"23% which may be very useful for clinicians when establishing the initial VPA dosage regimen."	( Population estimation of valproic acid clearance in adult patients using routine clinical pharmacokinetic data. Blanco-Serrano, B; Domínguez-Gil, A; García-Sánchez, MJ; Otero, MJ; Santos-Buelga, D; Serrano, J, 1999)	0.61
" ED50 of nimodipine could not be established since a dose-response relationship was not obtained."	( Anticonvulsant profile of nimodipine and nitrendipine against pentylenetetrazole induced seizures in rats. Balakrishnan, S; Bhargava, VK; Pandhi, P, 1999)	0.3
" The VPA dosage was then adjusted based on the unbound rather than the total VPA serum concentration; the patient eventually improved and was discharged from the hospital."	( Elevated free fractions of valproic acid in a heart transplant patient with hypoalbuminemia. Haroldson, JA; Kramer, LE; Lake, KD; Wolff, DL, 2000)	0.6
" The nonlinear pharmacokinetic and protein saturation characteristics of VPA may result in nonproportional elevations in unbound drug, and subsequent increases in adverse effects, when dosage adjustments are based solely on measurement of total VPA serum concentrations in patients with hypoalbuminemia."	( Elevated free fractions of valproic acid in a heart transplant patient with hypoalbuminemia. Haroldson, JA; Kramer, LE; Lake, KD; Wolff, DL, 2000)	0.6
" In one group, dosage was adjusted to achieve serum AED concentration within a target range (10-20 microg/ml for PHT, 15-40 microg/ml for PB, 4-11 microg/ml for CBZ, and 40-100 microg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds."	( A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy. Bartoli, A; Cian, P; Fattore, C; Gatti, G; Jannuzzi, G; Monaco, F; Perucca, E, 2000)	0.31
" In most situations, even when highly clinically significant, they can be reversed with dosage reduction; drug discontinuation is rarely required."	( Hematologic toxicity of sodium valproate. Acharya, S; Bussel, JB, )	0.13
" After lamotrigine was added for better seizure control and the dosage of gabapentin was tapered, anorgasmia improved."	( Improved sexual function in three men taking lamotrigine for epilepsy. Carwile, ST; Husain, AM; Miller, PP; Radtke, RA, 2000)	0.31
"Determining antiepileptic drug (AED) concentration in biological fluids and calculating its dosage on this basis is a long-term method in the treatment of epilepsy."	( [Therapeutic antiepileptic drug monitoring: thirteen years of experience in the Laboratory of Clinical Neuropharmacology in the Chair and Department of Developmental neurology]. Galas-Zgorzalewicz, B; Steinborn, B, 2000)	0.31
" Everyone received a drug dosage which gave an adequate therapeutic plasma concentration and satisfactory seizure control."	( [Bimodal evoked potentials during long-term therapy with conventional or slow release preparations of carbamazepine and valproic acid in children and adolescents with epilepsy]. Zgorzalewicz, M, 2000)	0.52
"The study aimed to show whether autoinduction of valproate (VPA) along its beta-oxidation pathway occurred upon chronic dosing in humans."	( Apparent autoinduction of valproate beta-oxidation in humans. Andrews, JA; Cannell, GR; Dickinson, RG; Eadie, MJ; Hooper, WD; McLaughlin, DB, 2000)	0.31
" At each dose, one group of male rats was euthanized after 4-week dosage (4-week dose group) and the other two were mated with untreated females after 4 (7-week dose group) or 7 (10-week dose group) weeks of treatment with valproic acid and their fertility was evaluated."	( Effects of valproic acid on fertility and reproductive organs in male rats. Nishimura, T; Sakai, M; Yonezawa, H, 2000)	0.88
" The dosage of corticotropin was lower than previously reported."	( Current therapy for West syndrome in Japan. Ito, M; Seki, T; Takuma, Y, 2000)	0.31
"To evaluate plasma homocysteine (Hcy) concentrations in children receiving sodium valproate (VPA) and carbamazepine (CBZ), monotherapy, in comparison with healthy control subjects and to determine the possible relationship between Hcy levels and dosage and plasma concentrations of the antiepileptic drugs."	( Hyperhomocysteinemia in children treated with sodium valproate and carbamazepine. Chiarelli, F; Giuva, T; Morgese, G; Pascarella, R; Trotta, D; Verrotti, A, 2000)	0.31
"We studied the incidence of headache relief in our patients with migraine aged 16 years and younger treated with divalproex sodium prophylactically at our institution from July 1996 to December 1998 to determine medication dosage used, concomitant headache medications, and possible adverse effects."	( The efficacy of divalproex sodium in the prophylactic treatment of children with migraine. Brown, WD; Caruso, JM; Exil, G; Gascon, GG, 2000)	0.31
" Divalproex sodium dosage ranged from 15 mg/kg/day to 45 mg/kg/day."	( The efficacy of divalproex sodium in the prophylactic treatment of children with migraine. Brown, WD; Caruso, JM; Exil, G; Gascon, GG, 2000)	0.31
" TPM is introduced at 25 mg and increased with weekly 25mg/d increments to a minimum dosage of 200 mg/d."	( A multicenter, randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures. Aldenkamp, AP; Baker, G; Chadwick, D; Cooper, P; de Haan, GJ; Doelman, J; Duncan, R; Gassmann-Mayer, C; Hughson, C; Hulsman, J; Mulder, OG; Overweg, J; Pledger, G; Rentmeester, TW; Riaz, H; Wroe, S, 2000)	0.31
" Dosing occurred three times per day: immediately after breakfast, lunch, and dinner."	( Assessment of ganaxolone's anticonvulsant activity using a randomized, double-blind, presurgical trial design. Ganaxolone Presurgical Study Group. Abou-Khalil, BW; Blum, D; Data, JL; Laxer, K; Lee, DA; Monaghan, EP; Morrell, MJ, 2000)	0.31
" It can be concluded that nanoparticles loaded with valproic acid may help to reduce the toxic side effects of valproate therapy, not by reducing the therapeutically necessary dosage but by inhibition of formation of toxic metabolites."	( Influence of nanoparticles on the brain-to-serum distribution and the metabolism of valproic acid in mice. Darius, J; Meyer, FP; Sabel, BA; Schroeder, U, 2000)	0.78
" The mean average dosage of valproic acid was 1,250 mg daily."	( Valproic acid in prophylaxis of refractory migraine. Erdemoglu, AK; Ozbakir, S, 2000)	2.04
" The present study examined the LTG metabolic inhibition dose-response relationship with valproic acid (VPA) in eight patients with epilepsy with a view to using this to benefit the patient."	( Clinical study of lamotrigine and valproic acid in patients with epilepsy: using a drug interaction to advantage? Black, AB; Lam, E; Morris, RG; Westley, IS, 2000)	0.81
" Target maintenance dosage was 200 mg/day (lamotrigine) and 20 mg/kg/day (valproic acid), with adjustment from 100 to 500 mg/day (lamotrigine) and 10 to 60 mg/kg/day (valproate) based on investigators' judgment."	( Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy. Barrett, PS; Biton, V; Hammer, AE; Mirza, W; Montouris, G; Vuong, A, 2001)	0.54
"The loading dosage of intravenous valproate required to achieve a desired serum concentration in neonates is not known."	( Intravenous valproate dosing in neonates. Alfonso, I; Alvarez, LA; Dunoyer, C; Gilman, J; Papazian, O; Yelin, K, 2000)	0.31
" On day 7 of each dosing phase, serial blood samples and all urine passed over the 12-h inter-dosing interval were collected."	( Steady-state dispositions of valproate and diflunisal alone and coadministered to healthy volunteers. Addison, RS; Dickinson, RG; Eadie, MJ; Hooper, WD; Parker-Scott, SL, 2000)	0.31
" Similarly, valproate combined with antipsychotics provided greater improvement in mania than antipsychotic medication alone and resulted in lower dosage of the antipsychotic medication."	( Novel treatments for bipolar disorder. Bowden, CL, 2001)	0.31
"Divalproex therapy initiated at 500 mg/day (250 mg twice daily), with adjustment in dose and dosing frequency possible after 1 to 3 days."	( Safety of divalproex sodium in migraine prophylaxis: an open-label, long-term study. Long-term Safety of Depakote in Headache Prophylaxis Study Group. Collins, SD; Silberstein, SD, 1999)	0.3
" On day 7 of each dosing phase, serial plasma and 24 h urine samples were collected for analysis."	( Effect of naproxen co-administration on valproate disposition. Addison, RS; Dickinson, RG; Eadie, MJ; Hooper, WD; Parker-Scott, SL, 2000)	0.31
" The patients were divided into two groups based on the initial dosing regimen."	( Tolerability of oral loading of divalproex sodium in child psychiatry inpatients. Feaster, CS; Good, CR; Krecko, VF, 2001)	0.31
" The majority of these side effects occurred in patients with drug levels > or = 90 ug/mL and were noted to improve with 1-2 days of therapy +/- dosage adjustment."	( Tolerability of oral loading of divalproex sodium in child psychiatry inpatients. Feaster, CS; Good, CR; Krecko, VF, 2001)	0.31
" The dosage of other mood stabilizer drugs remained unchanged throughout the 6-week follow-up."	( [Effectiveness and safety of topiramate in treatment-resistant bipolar disorder]. Arrufat, E; García-Castrillón, A; García-Parés, G; Gilabert, A; Luna, MJ; Rodríguez, A; Vieta, E, )	0.13
" All patients were put on sodium valproate in dosages (lower than usual) for initial control and further lower maintenance dosage and response evaluated."	( Juvenile myoclonic epilepsy--an experience from north western India. Panagariya, A; Sardana, V; Sureka, RK, 2001)	0.31
" Rates of metabolism in children may be much faster than in nonelderly adults, requiring dosing adjustments to ensure enough medication is used to control seizures."	( Treatment of epilepsy in 3 specialized populations. Leppik, IE, 2001)	0.31
" Thus, after dosing rats with VPA or F-VPA, animals were sacrificed (0."	( Effect of alpha-fluorination of valproic acid on valproyl-S-acyl-CoA formation in vivo in rats. Benet, LZ; Chiellini, G; Grillo, MP; Tonelli, M, 2001)	0.59
" Four of them suffered persistent seizures despite optimal VPA dosage and needed the addition of a second drug (lamotrigine in three cases, clobazam in one case)."	( Evolution of juvenile myoclonic epilepsy treated from the outset with sodium valproate. Calleja, S; Lahoz, CH; Ribacoba, R; Salas-Puig, J, 2001)	0.31
"02) and VPA dosage greater than 1,000 mg/day (p<0."	( Prevalence and risk of thrombocytopenia with valproic acid: experience at a psychiatric teaching hospital. Branch, RA; Coley, KC; Conley, EL; Dapos, SV; Maxwell, R; Pollock, BG, 2001)	0.57
" The medication and dosing strategy was well tolerated."	( Divalproex loading in the treatment of cocaine dependence. Brady, KT; Henderson, S; Malcom, R; Measom, M; Myrick, H, )	0.13
" A relatively large initial VPA dosage could possibly be the culprit."	( Valproate-induced encephalopathy. Chen, WT; Liao, KK; Yen, DJ; Yu, HY, 2001)	0.31
" This study of the population pharmacokinetics of lamotrigine in patients using the drug clinically provides useful data and should lead to better dosage individualization for lamotrigine."	( Population pharmacokinetics of lamotrigine. Chan, V; Ilett, KF; Morris, RG; Tett, SE, 2001)	0.31
" Increasing clinical experience will more fully elucidate indications for, and optimal dosing of, naloxone in valproic acid toxic states."	( Use of naloxone in valproic acid overdose: case report and review. Francis, EH; Roberge, RJ, 2002)	0.86
" Our results suggest that the dosage of valproate in patients with coronary artery disease treated with molsidomine should be decreased."	( Molsidomine enhances the protective activity of valproate against pentylenetetrazole-induced seizures in mice. Arent, K; Kleinrok, Z; Tutka, P; Wielosz, M; Łuszczki, J, 2002)	0.31
"A 3-week, randomized, double-blind trial compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day in divided doses) for the treatment of patients hospitalized for acute bipolar manic or mixed episodes."	( Olanzapine versus divalproex in the treatment of acute mania. Altshuler, LL; Baker, RW; Breier, A; Gilmore, JA; Ketter, TA; Milton, DR; Risser, R; Suppes, T; Tohen, M; Tollefson, GA; Zarate, CA, 2002)	0.31
" Repeating the EEG after the dosage has been lowered will help avoiding unnecessary recurrence of seizures."	( [Television, children and epilepsy]. Dekker, E; Stroink, H; Trenité, DG, 2002)	0.31
" The peak concentration (Cmax) of CZP and the time intervals from dosing to Cmax (Tmax) were 20."	( Pharmacokinetic and pharmacodynamic effects of clonazepam in children with epilepsy treated with valproate: a preliminary study. Wang, L; Wang, XD, 2002)	0.31
" Valproate is available in different dosage forms for parenteral and oral use."	( Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. Perucca, E, 2002)	0.31
" Male Sprague-Dawley rats were dosed with 500 mg/kg/day sodium valproate: after necropsy, mRNA was subjected to suppression PCR subtractive hybridization, identifying 8 up-regulated and 14 down-regulated mRNA species."	( Differential gene expression in rats following subacute exposure to the anticonvulsant sodium valproate. Barber, P; Bugelski, P; Cockburn, CL; Gibson, G; Horner, E; Lord, P; Plant, N, 2002)	0.31
"5 mg daily until a total dosage of either 75 mg or 100 mg was obtained."	( Lamotrigine use in geriatric patients with bipolar depression. Conn, DK; Robillard, M, 2002)	0.31
" One patient did develop coarse hand tremor that improved when the lamotrigine dosage was decreased."	( Lamotrigine use in geriatric patients with bipolar depression. Conn, DK; Robillard, M, 2002)	0.31
"Experimental challenge-rechallenge, within-subjects repeated measures, before and at the end of 14 days of treatment with valproate at a dosage of 625 mg/d (reached gradually over the first 5 days)."	( Effects of short-term administration of valproate on serotonin-1A and dopamine receptor function in healthy human subjects. al-Said, K; Brooks, DL; Delva, NJ; Franklin, M; Hawken, ER; Lawson, JS; Merali, Z; Ravindran, AV, 2002)	0.31
" Divalproex was initiated at 15 mg/kg/day and titrated over 12 days to a maximum dosage of 30 mg/kg/day."	( Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia. Casey, DE; Daniel, DG; Sommerville, KW; Tracy, KA; Wassef, AA; Wozniak, P, 2003)	0.32
" They could be so severe in patients over 12 years of age that the stiripentol dosage could not be increased to 50 mg kg-1 j-1."	( [Long-term efficacy and tolerance of stiripentaol in severe myoclonic epilepsy of infancy (Dravet's syndrome)]. Chiron, C; Dellatolas, G; Dulac, O; Pons, G; Rey, E; Thanh, TN; Vincent, J, 2002)	0.31
" Although visual hallucinations have not been reported as an adverse effect of this agent, we describe three patients who experienced complex visual hallucinations and altered mental status after zonisamide treatment was begun or its dosage increased."	( Visual hallucinations associated with zonisamide. Akman, CI; Goodkin, HP; Riviello, JJ; Rogers, DP, 2003)	0.32
" Additionally, VPA pharmacokinetics are dependent on age, induction status, and formulation; so titration and dosing vary between individuals."	( Oral/intravenous maintenance dosing of valproate following intravenous loading: a simulation. Cloyd, JC; Collins, SD; Dutta, S; Granneman, GR, 2003)	0.32
" We performed a cross-sectional surveillance study on pediatric patients taking valproate to evaluate the relationship between carnitine levels and demographic data including age, daily dosage of valproate, number of antiepileptic drugs, body mass index, and feeding problems."	( Carnitine level in Chinese epileptic patients taking sodium valproate. Fok, TF; Fung, EL; Ho, CS; Lam, CW; Tang, NL, 2003)	0.32
" Three divided doses of FA on GD 7 and continuous dosing of FA from GD 5 through GD 10 substantially reduced the VPA-induced exencephaly in the fetuses."	( Amelioration of sodium valproate-induced neural tube defects in mouse fetuses by maternal folic acid supplementation during gestation. Padmanabhan, R; Shafiullah, MM, 2003)	0.32
" The present investigation was undertaken to design an oral dosage form that would provide once-daily administration with improved therapy and to explore the relationships between in vitro drug release and in vivo absorption."	( Once-a-day controlled-release dosage form of divalproex sodium I: formulation design and in vitro/in vivo investigations. Cheskin, HS; Engh, KR; Poska, RP; Qiu, Y, 2003)	0.32
"This 47-week, randomized, double-blind study compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day) for manic or mixed episodes of bipolar disorder (N=251)."	( Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study. Altshuler, L; Baker, RW; Brown, E; Frye, M; Ketter, TA; Risser, RC; Schuh, LM; Suppes, T; Tohen, M; Zajecka, J; Zarate, CA, 2003)	0.32
" The valproate was under therapeutic blood level when zotepine dosage was raised to 200 mg/day, and hypothermia occurred."	( Two case studies of hypothermia induced by an increased dosage of zotepine in a combination therapy. Chen, KC; Chen, PS; Yang, MJ; Yang, YK; Yeh, TL, 2003)	0.32
" A final dosage of 60 mg/kg was used."	( Acute psychosis associated with levetiracetam. Karagianni, J; Lazopoulou, D; Michelakou, D; Youroukos, S, 2003)	0.32
" For those who were treated, they were easily controlled on a low dose of carbamazepine (median dosage of 12."	( Benign childhood epilepsy with centrotemporal spikes: a study of 50 Chinese children. Chan, KY; Ma, CK, 2003)	0.32
"Previous studies have examined the safety and tolerability of oral-loaded divalproex sodium in the treatment of acute mania, but not the early efficacy of this dosing strategy."	( The safety and early efficacy of oral-loaded divalproex versus standard-titration divalproex, lithium, olanzapine, and placebo in the treatment of acute mania associated with bipolar disorder. Baker, JD; Hirschfeld, RM; Sommerville, KW; Tracy, K; Wozniak, P, 2003)	0.32
" These trials demonstrated a consistent pattern of efficacy and the delayed-release form improved tolerability while offering a twice-daily dosing schedule."	( Divalproex sodium extended-release for the prophylaxis of migraine headache. Freitag, FG, 2003)	0.32
" Mean dosage of VPA was 1137."	( Thrombocytopenia during valproic acid treatment in young patients with new-onset bipolar disorder. Campanella, D; De Berardis, D; Ferro, FM; Gambi, F; Grimaldi, MR; La Rovere, R; Matera, V; Pacilli, AM; Salerno, RM; Sepede, G, 2003)	0.63
" In the present study, the authors observed impairment in platelet release of ATP and aggregation that correlated with both VPA dosage and plasma levels."	( Thrombocytopenia during valproic acid treatment in young patients with new-onset bipolar disorder. Campanella, D; De Berardis, D; Ferro, FM; Gambi, F; Grimaldi, MR; La Rovere, R; Matera, V; Pacilli, AM; Salerno, RM; Sepede, G, 2003)	0.63
" We evaluated the pharmacokinetics of valproate (protein binding and clearance) across a wide dosage range in the elderly and measured the impact of this on drug-related side effects using a single-blind within-subject study design in 6 healthy elderly volunteers (aged 65-76 years)."	( Dose-related pharmacokinetics and pharmacodynamics of valproate in the elderly. Felix, S; Hardy, BG; Naranjo, CA; Sproule, BA, 2003)	0.32
" Valproates in dosage 30-60 mg/kg daily were highly effective for stopping epileptic seizures."	( [Electroclinical characteristics of Landau-Kleffner syndrome]. Glukhova, LIu; Kholin, AA; Mukhin, KIu; Petrukhin, AS; Zaĭtseva, MN, 2003)	0.32
" Reduction of the VPA dosage led to clinical and laboratory parameter improvement, while discontinuation of therapy was not necessary."	( Valproic-acid-induced thrombocytopenia and hepatotoxicity: discontinuation of treatment? Lackmann, GM, 2004)	0.32
" Patients were converted during an	( Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy. Hammer, AE; Kaminow, L; Schimschock, JR; Vuong, A, 2003)	0.32
"4% in the high dosage groups."	( Chemically induced supernumerary lumbar ribs in CD-1 mice: size distribution and dose response. Branch, S; Chernoff, N; Rogers, JM; Setzer, RW, 2004)	0.32
" Serial blood samples were obtained over 120 h post-dose in order to calculate LTG kinetic parameters including area under the concentration-time curve, apparent oral clearance, elimination half-life and percent inhibition of LTG clearance at each dosage level of VPA."	( Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetics: implications for conversion to lamotrigine monotherapy. Gidal, BE; Maloney, K; Parnell, J; Sale, M; Sheth, R, 2003)	0.32
" These data provide useful information to develop a dosing algorithm to facilitate conversion to LTG monotherapy."	( Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetics: implications for conversion to lamotrigine monotherapy. Gidal, BE; Maloney, K; Parnell, J; Sale, M; Sheth, R, 2003)	0.32
" However, there is no information available on the number of therapeutic abortions, or the different types of epilepsy or drug dosage in the two treatment groups."	( Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation-wide, population-based register study. Källén, B; Wide, K; Winbladh, B, 2004)	0.54
" The patient's regular physicians managed all treatment decisions, including decisions on dosage and plasma level measurements of sodium valproate and decisions regarding discontinuation."	( Sodium valproate in aggressive behaviour in dementia: a twelve-week open label follow-up study. Duivenvoorden, HJ; Duursma, SA; Eikelenboom, P; Haffmans, PM; Jansen, PA; Sival, RC, 2004)	0.32
" The aim of the present work was to evaluate the ability of TDM using model-based, goal-oriented Bayesian adaptive control for help in planning, monitoring, and adjusting individualized VAL dosing regimens."	( Nonparametric population modeling of valproate pharmacokinetics in epileptic patients using routine serum monitoring data: implications for dosage. Bondareva, IB; Jelliffe, RW; Sokolov, AV; Tischenkova, IF, 2004)	0.32
" In Porsteinsson 2001, although the physicians having direct responsibility for patient care were blinded, a non-blinded physician, who had no direct contact with these physicians, adjusted divalproex sodium dosage on the basis of reports from blinded raters."	( Valproic acid for agitation in dementia. Cameron, M; Lonergan, ET; Luxenberg, J, 2004)	1.77
" If a dosage of AEDs in pregnant women with epilepsy is reduced to a reasonable minimum and the monotherapy is preferred, the risk of congenital malformations in their offspring can be minimized."	( [Effect of anti-epileptic drugs on human placenta and the fetus]. Semczuk, M; Semczuk-Sikora, A, 2004)	0.32
" Reduction in VPA dosage in the third patient produced no improvement."	( Reversible parkinsonism with normal beta-CIT-SPECT in patients exposed to sodium valproate. Clough, P; Duncan, S; Easterford, K; Fallon, K; Kellett, M, 2004)	0.32
"To assess the safety, efficacy, and tolerability of switching from a multiple dose preparation of divalproex sodium delayed release (DR) to once-daily dosing with divalproex sodium extended release (ER) in patients with schizophrenia already receiving the standard DR formulation."	( A study of the safety, efficacy, and tolerability of switching from the standard delayed release preparation of divalproex sodium to the extended release formulation in patients with schizophrenia. Citrome, L; Dinakar, H; Roy, B; Tremeau, F; Wynn, PS, 2004)	0.32
"Adrenocorticotropic hormone (ACTH) is probably effective for the short-term treatment of infantile spasms, but there is insufficient evidence to recommend the optimum dosage and duration of treatment."	( Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Adams-Webber, T; Ashwal, S; Ballaban-Gill, K; Baram, TZ; Duchowny, M; Hirtz, D; Mackay, MT; Pellock, JM; Shields, WD; Shinnar, S; Snead, OC; Stephens, D; Weiss, SK; Wyllie, E, 2004)	0.32
" Once-daily administration of divalproex sodium extended-release tablets (doses ranged from 250 to 1750 mg) in older children and adolescents produced relatively flat plasma valproic acid concentration-time profiles over the entire 24-hour dosing interval, similar to the pharmacokinetic performance of this formulation in adults."	( Divalproex-ER pharmacokinetics in older children and adolescents. Biton, V; Conway, JM; Dutta, S; Kearns, GL; Reed, MD; Sallee, FR; Zhang, Y, 2004)	0.52
"The aims of our study were to evaluate whether deficits in color vision exist in epileptic adolescents, to study if monotherapy with valproic acid (VPA) and carbamazepine (CBZ) can affect color vision, and to determine the possible relationship between abnormal color vision tests and AEDs dosage and their serum concentrations."	( Color vision in epileptic adolescents treated with valproate and carbamazepine. Chiarelli, F; Gallenga, PE; Lobefalo, L; Morgese, G; Priolo, T; Rapinese, M; Trotta, D; Verrotti, A, 2004)	0.53
" Pearson's correlation test was performed to correlate chromatic sense and perimetric data and AEDs dosage and serum concentrations."	( Color vision in epileptic adolescents treated with valproate and carbamazepine. Chiarelli, F; Gallenga, PE; Lobefalo, L; Morgese, G; Priolo, T; Rapinese, M; Trotta, D; Verrotti, A, 2004)	0.32
" Although SNR incidence generally increased with increasing dose of RA, a strict dose-response relationship was lacking."	( Experimental studies on cervical and lumbar ribs in mouse embryos. Padmanabhan, RR; Rengasamy, P, 2004)	0.32
" In vivo hydrolysis of VPA-G was clearly shown by the existence of VPA in plasma after dosing of VPA-G to rats, and its inhibition by carbapenems was also clearly shown by the negligible levels of VPA in rat plasma after coadministration of carbapenems and VPA-G."	( Mechanism of the drug interaction between valproic acid and carbapenem antibiotics in monkeys and rats. Inagaki, H; Koike, M; Kominami, G; Mizobuchi, M; Nakajima, Y; Nakamura, M; Takagi, H; Yamaguchi, T, 2004)	0.59
" The simple method was applied to the analysis of valproic acid in plasma of dosed patients using only small amount of sample (10-50 microl plasma)."	( Simple and sensitive fluorimetric liquid chromatography method for the determination of valproic acid in plasma. Chen, CC; Kou, HS; Lin, MC; Wu, HL; Wu, SM, 2004)	0.8
" One group of 15 subjects was dosed after a 10 h overnight fast and another group of 24 subjects was dosed after a high-fat breakfast."	( Comparison of the bioavailability of 250 and 500 mg divalproex sodium extended-release tablets in healthy volunteers. Dutta, S; Lee, LL; O'Dea, R; Zhang, Y, 2004)	0.32
" A meta-analysis of divalproex-ER/divalproex relative bioavailability across five studies under different meal conditions and divalproex dosing frequencies was performed."	( Bioavailability of divalproex extended-release formulation relative to the divalproex delayed-release formulation. Dutta, S; Zhang, Y, 2004)	0.32
" The severity of the cognitive side effects of TPM may be related to dosing to a certain extent, but this relationship may be disclosed only with larger sample sizes."	( Cognitive profile of topiramate as compared with lamotrigine in epilepsy patients on antiepileptic drug polytherapy: relationships to blood serum levels and comedication. Elger, CE; Helmstaedter, C; Kockelmann, E, 2004)	0.32
" Recently, a new extended-release (ER) formulation of divalproex sodium has become available, which allows for once-daily dosing and provides prolonged therapeutic serum levels."	( Clinical comparison of extended-release divalproex versus delayed-release divalproex: pooled data analyses from nine trials. Centorrino, F; Collins, MA; Smith, MC; Welge, JA, 2004)	0.32
" A regimen was categorized as toxic if the patient experienced side effects that led to a dosage change or discontinuation of LTG."	( Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy. Adams, DJ; Bazil, CW; Buchsbaum, R; Du, Y; Hager, M; Hirsch, LJ; Morrell, MJ; Resor, SR; Spencer, HT; Straka, T; Weintraub, D, 2004)	0.32
" HIV type 1 (HIV-1)-infected patients receiving EFV or lopinavir-ritonavir (LPV/r) had 9 or 10 blood samples drawn over 8 to 24 h of a dosing interval at steady state before and after receiving 250 mg of VPA twice daily for 7 days."	( Effects of valproic acid coadministration on plasma efavirenz and lopinavir concentrations in human immunodeficiency virus-infected adults. Cruttenden, K; DiCenzo, R; Gelbard, H; Morse, G; Peterson, D; Riggs, G; Schifitto, G, 2004)	0.71
" CBZ, PB, OXC, and VPA displayed a dose-response relation."	( Fracture risk associated with use of antiepileptic drugs. Mosekilde, L; Rejnmark, L; Vestergaard, P, 2004)	0.32
" The adequate dosage of VPD (Depamide, 300 mg) is 4 to 6 tablets in acute manic phases, 2 to 4 tablets in long term treatment, 1 to 3 tablets in depressive episode."	( [Valpromide, Valproic acid and removal of small intestine in the treatment of a chronic depression: a case report]. Benjelloun, G; Blandin, K; Fossati, P, )	0.5
"5 mg/L for the morning dosing and 1728 mg x hr/L, 84."	( Pharmacokinetics and safety of extended-release divalproex sodium tablets: morning versus evening administration. Cavanaugh, JH; Dutta, S; Reed, RC, 2004)	0.32
"A dosing algorithm was used to guide the conversion of 77 patients with epilepsy (16 years of age) from valproate monotherapy through lamotrigine adjunctive therapy at 200mg daily to lamotrigine monotherapy at 500 mg daily in an open-label study comprising a lamotrigine escalation phase (8 weeks), a valproate withdrawal phase (6 weeks), and a lamotrigine monotherapy phase (4 weeks)."	( A dosing algorithm for converting from valproate monotherapy to lamotrigine monotherapy in patients with epilepsy. Biton, V; Blum, D; Hammer, AE; Messenheimer, JA; Natarajan, S; Sale, ME; Vuong, A, 2005)	0.33
" The dosage schedule was: 5 mg every day or every second day for 14 days, increased by 5 mg every 14th day to 25 mg a day."	( Lamotrigine-induced rash--worth a rechallenge. Dam, M; P-Codrea Tigaran, S; Sidenius, P, 2005)	0.33
"We report a series of 102 adult patients who received standardized high dosage intravenous valproate in various emergency situations, including status epilepticus."	( Intravenous valproate as an innovative therapy in seizure emergency situations including status epilepticus--experience in 102 adult patients. Peters, CN; Pohlmann-Eden, B, 2005)	0.33
" Steady-state dosing of zonisamide (200mg twice daily) had no statistically significant effect on the mean (+/- SD) maximum observed plasma concentration (C(max)) [70."	( Lack of pharmacokinetic interactions between steady-state zonisamide and valproic acid in patients with epilepsy. Brodie, M; Grundy, JS; Levy, RH; Ragueneau-Majlessi, I; Shah, J; Smith, D, 2005)	0.56
"There is no apparent clinically significant effect of steady-state dosing of zonisamide on valproic acid pharmacokinetics, and valproic acid did not appear to affect the pharmacokinetics of zonisamide, indicating that no dosage adjustment of either drug should be required when they are used in combination in patients with epilepsy."	( Lack of pharmacokinetic interactions between steady-state zonisamide and valproic acid in patients with epilepsy. Brodie, M; Grundy, JS; Levy, RH; Ragueneau-Majlessi, I; Shah, J; Smith, D, 2005)	0.78
" The concordance is apparent both by en masse correlation of fold-changes and by detailed similarity of dose-response profiles of individual genes."	( Association of valproate-induced teratogenesis with histone deacetylase inhibition in vivo. Berman, MG; Gentleman, RC; Green, JB; Gurvich, N; Klein, PS; Wittner, BS, 2005)	0.33
" We developed a simple dosing scheme using valproate sodium injection (VPA-IV) and divalproex sodium extended-release (VPA-ER) tablets to minimize the time required for initiation of therapy, without increasing the likelihood of seizures and adverse effects."	( Successful initiation of combined therapy with valproate sodium injection and divalproex sodium extended-release tablets in the epilepsy monitoring unit. Boggs, JG; Preis, K, 2005)	0.33
"Defining a quantitative and reliable relationship between in vitro drug release and in vivo absorption is highly desired for rational development, optimization, and evaluation of controlled-release dosage forms and manufacturing process."	( Once-a-day extended-release dosage form of divalproex sodium III: development and validation of a Level A in vitro-in vivo correlation (IVIVC). Cao, G; Dutta, S; Granneman, GR; Qiu, Y; Samara, E, 2005)	0.33
" Unlike the situation for the other drugs, the malformation rate in those exposed to valproate increased with increasing maternal drug dosage (P<0."	( Maternal valproate dosage and foetal malformations. Eadie, MJ; Vajda, FJ, 2005)	0.33
"To examine the metabolic effects of three divalproex dosing regimens in patients with migraine."	( Effect of divalproex on metabolic parameters is dose related in migraine prophylaxis. Giordano, S; Green, MW; Jafari, M; Jiang, P; Smith, TB, 2005)	0.33
" No tolerance was evident in the intravenous pentylenetetrazol test after twice-daily dosing of ABT-769 (0."	( Preclinical profiling and safety studies of ABT-769: a compound with potential for broad-spectrum antiepileptic activity. Bennani, Y; Bitner, RS; Chemburkar, SR; Chen, J; Curzon, P; Dart, MJ; Decker, MW; Durmuller, N; Fox, GB; Giardina, WJ; Grayson, GK; Harris, RR; Hui, JY; Jolly, R; Komater, VA; Ku, Y; Lockwood, M; Marsh, KC; Miner, HM; Nikkel, AL; Pan, JB; Pu, YM; Radek, RJ; Roux, S; Sullivan, JP; Wang, L; Waring, JF, 2005)	0.33
" Following valproic acid (VPA, 30 mg/kg), the population spike amplitude and the EPSP slope in response to the stimulus were markedly reduced in the dentate gyri both of SR and of SS gerbils, although this dosage of VPA had no effect in low stimulus currents in SS gerbils."	( Valproic acid reduces enhanced vesicular glutamate transporter immunoreactivities in the dentate gyrus of the seizure prone gerbil. Choi, SY; Kang, JH; Kang, TC; Kim, DS; Kim, DW; Kim, JE; Kwak, SE; Kwon, OS; Won, MH, 2005)	2.16
" Dosing recommendations in the case of a missed or delayed dose are both formulation and dose dependent."	( The use of Monte Carlo simulations to study the effect of poor compliance on the steady state concentrations of valproic acid following administration of enteric-coated and extended release divalproex sodium formulations. Ahmad, AM; Barr, WH; Douglas Boudinot, F; Garnett, WR; Reed, RC, 2005)	0.54
" However, these issues deserve further investigation in controlled, randomized and probably multicentre trials to evaluate the clinical value and the appropriate dosage of L-carnitine in each of these conditions."	( Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence? Gris, M; Lheureux, PE; Penaloza, A; Zahir, S, 2005)	0.59
"In an observational study under routine clinical setting data after administration of once daily evening dosing of valproate sustained release minitablets were recorded in 359 patients with epilepsy aged between 12 and 86 years."	( [Valproate sustained release in the treatment of epilepsy]. Fraunberger, B; Stefan, H, 2005)	0.33
"A 56-year-old woman with poorly controlled epilepsy, receiving valproate at subtherapeutic levels for 6 years, developed a life-threatening hyperammonemic coma following a moderate dosage increase."	( Acute hyperammonemic coma with chronic valproic acid therapy. Abramson, RK; Cuturic, M, 2005)	0.6
" The medication dosage varied from 1 to 20 mg/kg daily."	( [The efficacy of topiramate (topamax) in the treatment of resistant epilepsy in children]. Belousova, ED; Dorofeeva, MIu; Ermakov, AIu, 2005)	0.33
"Successful long-term treatment of patients with epilepsy requires selection of an appropriate antiepileptic regimen, optimal dosing and patient compliance."	( Progress in pharmaceutical development presentation with improved pharmacokinetics: a new formulation for valproate. Genton, P, 2005)	0.33
" Linear regression analysis of dose-response relationship between the doses of 2-PMPA and their corresponding threshold values allowed the calculation of threshold increasing dose by 20% (TID20), which was 109."	( 2-phosphonomethyl-pentanedioic acid (glutamate carboxypeptidase II inhibitor) increases threshold for electroconvulsions and enhances the antiseizure action of valproate against maximal electroshock-induced seizures in mice. Czuczwar, SJ; Luszczki, JJ; Mohamed, M, 2006)	0.33
"1% and never over taking dosed the antiepileptic drug 96."	( Chrono impact versus enteric coated valproate in Thai epileptic patients. Arayawichanon, A; Asawavichenjinda, T; Chaisewikul, R; Kijjarak, R; Maneesuk, S; Poungvarin, N; Silpakit, O; Sirimaharaj, S; Thammasupapong, S; Tiemkao, S; Towanabut, S, 2005)	0.33
" The DFL for divalproex-ER dosed as a q12h regimen was 22% less than that for once-daily divalproex-ER (P=0."	( Every-12-hour administration of extended-release divalproex in patients with epilepsy: impact on plasma valproic acid concentrations. Cavanaugh, JH; Dutta, S; Granneman, GR; Locke, C; Reed, RC, 2006)	0.55
" Principal component analysis (PCA) of the metabonomics data showed clustering of the dosed groups away from the controls for the urine samples."	( An integrated study of acute effects of valproic acid in the liver using metabonomics, proteomics, and transcriptomics platforms. Beger, RD; Dragan, YP; Edmondson, RD; Fuscoe, JC; Han, T; Hansen, DK; Jones, RC; Schnackenberg, LK; Taylor, JT; Thyparambil, S; Tong, W, 2006)	0.6
" A new formulation specifically adapted for children, Chronosphere, administrated once or twice daily, is a modified-release formulation of valproate that minimizes fluctuations in serum drug concentrations during a dosage interval."	( Valproate as a mainstay of therapy for pediatric epilepsy. Guerrini, R, 2006)	0.33
"The goal of our study was to evaluate clinical and serum valproic acid concentration changes in patients following overnight conversion from delayed-release sodium valproate (VPA-DR) to the same daily dosage of extended-release sodium valproate (VPA-ER)."	( Conversion from delayed-release sodium valproate to extended-release sodium valproate: initial results and long-term follow-up. Lehman, EB; McCabe, PH; McNew, CD; Michel, NC, 2006)	0.58
" Thirty patients were converted to twice-daily dosing and 11 were converted to once-daily dosing."	( Conversion from delayed-release sodium valproate to extended-release sodium valproate: initial results and long-term follow-up. Lehman, EB; McCabe, PH; McNew, CD; Michel, NC, 2006)	0.33
" No significant difference in percentage change in serum trough valproic acid level was observed when comparing dosing frequency of VPA-DR, total daily dosage of VPA, conversion to once-daily versus twice-daily VPA-ER, or presence of enzyme-inducing agents."	( Conversion from delayed-release sodium valproate to extended-release sodium valproate: initial results and long-term follow-up. Lehman, EB; McCabe, PH; McNew, CD; Michel, NC, 2006)	0.57
" Dosing of VPA-ER either once-daily or twice-daily is acceptable."	( Conversion from delayed-release sodium valproate to extended-release sodium valproate: initial results and long-term follow-up. Lehman, EB; McCabe, PH; McNew, CD; Michel, NC, 2006)	0.33
"Varying the concentration of selected factors alters the induction properties of steroid receptors by changing the position of the dose-response curve (or the value for half-maximal induction=EC(50)) and the amount of partial agonist activity of antisteroids."	( Effects of acetylation, polymerase phosphorylation, and DNA unwinding in glucocorticoid receptor transactivation. Chow, C; Kim, Y; Pommier, YG; Simons, SS; Sun, Y, 2006)	0.33
" Since VPA CL/F is known to increase with increasing dosage, a lower VPA dosage in elderly patients comedicated with enzyme inducers compared with controls may have contributed to differences in CL/F between the two groups."	( The influence of old age and enzyme inducing comedication on the pharmacokinetics of valproic acid at steady-state: A case-matched evaluation based on therapeutic drug monitoring data. Battino, D; Croci, D; Fattore, C; Mamoli, D; Messina, S; Perucca, E, 2006)	0.56
" VPA clearance in elderly patients receiving enzyme inducing AEDs was lower than in controls, the difference being probably due to an influence of age as well as to the fact that mean VPA dosage was lower in these patients than in controls."	( The influence of old age and enzyme inducing comedication on the pharmacokinetics of valproic acid at steady-state: A case-matched evaluation based on therapeutic drug monitoring data. Battino, D; Croci, D; Fattore, C; Mamoli, D; Messina, S; Perucca, E, 2006)	0.56
" Conversely, for divalproex-ER dosed once-daily in the evening, for example 8 PM, a blood draw 12 to 15 hours later (ie, 8 to 11 AM) will give a plasma VPA concentration value that is 18% to 25% higher, on average, than the trough value."	( Does it really matter when a blood sample for valproic acid concentration is taken following once-daily administration of divalproex-ER? Dutta, S; Reed, RC, 2006)	0.59
"Mean dosage of valproic acid was 800 mg/d in both groups (13 mg/kg and 12."	( Comparison of valporic acid efficacy in familial versus sporadic cases of juvenile myoclonic epilepsy. Mohammad Ali, S; Motamedi, M; Rahmat, M, 2006)	0.69
" The aims of our study were to evaluate whether color vision and macular function are impaired in epileptic adolescents, to study if the monotherapy with valproic acid (VPA) and carbamazepine (CBZ) can affect color vision and macular function and to determine the possible relationship between color vision, retinal function and antiepileptic drugs (AEDs) dosage and their serum concentrations."	( Color vision and macular recovery time in epileptic adolescents treated with valproate and carbamazepine. Chiarelli, F; Gallenga, PE; Iannetti, P; Lobefalo, L; Spalice, A; Tocco, AM; Verrotti, A, 2006)	0.53
" Mean VPA dosage was of approximately 870 mg/day (approximately 22 mg/kg/day) and mean VPA concentration was of approximately 89 mg/l at 12 h post-dose and of 54 mg/l at 24 h post-dose."	( Conventional and sustained-release valproate in children with newly diagnosed epilepsy: a randomized and crossover study comparing clinical effects, patient preference and pharmacokinetics. Adín, J; Armijo, JA; Arteaga, R; Herranz, JL, 2006)	0.33
"Phenytoin dosing is critical in cancer patients as to decreased absorption secondary to chemotherapy-induced gastrointestinal toxicity, increased phenytoin metabolism in the liver secondary to chemotherapy, extreme patient profile that falls outside the predicted pharmacokinetic population, frequent hypoalbuminaemia and polydrug treatment."	( Interactions of serum albumin, valproic acid and carbamazepine with the pharmacokinetics of phenytoin in cancer patients. Beijnen, JH; Boogerd, W; Huitema, AD; Joerger, M; Schellens, JH; van der Sande, JJ, 2006)	0.62
" They have been controlled after increasing her dosage to 600mg/day."	( The efficacy of sodium valproate and a MRA finding in confusional migraine. Fujita, M; Fujiwara, J; Maki, T; Shibasaki, K; Shigeta, M; Takahashi, M; Takahashi, N, 2007)	0.34
" Also discussed are findings concerning the continuation of acute treatments, including antidepressants, into the maintenance phase; dosage adjustments for maintenance treatment; the rationale for combination treatments; and implications of comorbid substance abuse and strategies for its management."	( Maintenance treatment of bipolar disorder: Applying research to clinical practice. Chou, JC; Fazzio, L, 2006)	0.33
" At many institutes, especially children are treated as inpatients until the desired dosage is reached."	( Oral rapid loading of valproic acid--an alternative to the usual saturation scheme? Bell, N; Gerstner, T; König, SA; Longin, E, 2006)	0.65
" Furthermore, most studies have used the therapeutic range (50-100 mg/L) for seizure disorders to guide dosage in the psychiatric disorders, although study outcomes have suggested the need to redefine a threshold concentration in the different psychiatric conditions."	( Therapeutic monitoring of valproate in psychiatry: how far have we progressed? Chetty, M; Fleming, J, )	0.13
" Daily dosage was initiated at 25 mg/kg, increased 500 mg on day 3, and adjusted to serum valproate concentrations of 85 to 125 microg/mL."	( A randomized, placebo-controlled, multicenter study of divalproex sodium extended release in the treatment of acute mania. Abi-Saab, W; Bowden, CL; Calabrese, JR; Collins, MA; Rubenfaer, LM; Saltarelli, M; Swann, AC; Wozniak, PJ, 2006)	0.33
" The satisfying outcome after a sudden and complete withdrawal of LTG in both cases encouraged us to perform the switch from LTG to VPA systematically by discontinuing LTG abruptly and building up the VPA maintenance dosage very rapidly in the following five consecutive patients who required this exchange."	( How to replace lamotrigine with valproate. Steinhoff, BJ, 2006)	0.33
" Although the valproic acid dosage was increased, valproic acid levels did not return to the therapeutic range."	( Meropenem -valproic acid interaction in patients with cefepime-associated status epilepticus. Casteels, M; De Troy, E; Meersseman, W; Spriet, I; Willems, L; Wilmer, A, 2007)	1.09
" Measuring antiepileptic drug levels in body fluids (therapeutic drug monitoring) is frequently used to optimise drug dosage for individual patients."	( Therapeutic monitoring of antiepileptic drugs for epilepsy. Dahl, ML; Kimland, E; Tomson, T, 2007)	0.34
" In this open study, 180 patients with newly-diagnosed, untreated epilepsy were randomised to treatment with the antiepileptic drug selected by their physician either with or without therapeutic drug serum level monitoring as an aid to dosage adjustments."	( Therapeutic monitoring of antiepileptic drugs for epilepsy. Dahl, ML; Kimland, E; Tomson, T, 2007)	0.34
" Relation could not be established between the duration of VPA therapy, dosage of the drug, blood level of drug, age and sex of the patients and the auditory signs."	( Effects of valproic acid on hearing in epileptic patients. Akoglu, E; Duman, T; Incecik, F; Melek, I; Sangün, O, 2007)	0.73
"The value of t((1/2)F), defined as the time taken for the concentration to drop by one-half during a dosing interval (tau) at steady state, was derived using steady-state maximum (C(max)) and minimum (C(min)) plasma concentration and tau values, and calculated as ln(2)/(ln [C(max)/C(min)]/tau)."	( Functional half-life is a meaningful descriptor of steady-state pharmacokinetics of an extended-release formulation of a rapidly cleared drug : as shown by once-daily divalproex-ER. Dutta, S; Reed, RC, 2006)	0.33
" The contents of glutathion in the high dosage of TPM group (29."	( [An experimental study on hepatotoxicity of topiramate in young rats]. Chen, XM; Huang, J; Ren, RN; Ye, LY, 2007)	0.34
" High dosage of TPM or TPM along with VPA administration enhances the risk of the side effects."	( [An experimental study on hepatotoxicity of topiramate in young rats]. Chen, XM; Huang, J; Ren, RN; Ye, LY, 2007)	0.34
" No correlation was found between duration or dosage of treatment and BMI-SDS, height-SDS, or androgen level."	( Endocrine effects of valproate in adolescent girls with epilepsy. de Vries, L; Goldberg-Stern, H; Karasik, A; Kiviti, S; Landau, Z; Phillip, M, 2007)	0.34
"To describe the dose-concentration relationship of a continuous intravenous infusion of valproic acid (VPA) in pediatric patients when a dosing protocol is used."	( Clinical utility of a continuous intravenous infusion of valproic acid in pediatric patients. Baumann, RJ; Cook, AM; Farzam, F; Kuhn, RJ; Lewis, DA; Taylor, LM, 2007)	0.81
"To characterize possible pharmacokinetic interactions between the new antiepileptic drug carisbamate (RWJ-333369) and valproic acid (VPA) or lamotrigine (LTG) following multiple dosing in healthy subjects."	( An interaction study between the new antiepileptic and CNS drug carisbamate (RWJ-333369) and lamotrigine and valproic acid. Bialer, M; Chien, S; Doose, DR; Mertens, A; Novak, G; Solanki, B; Verhaeghe, T; Yao, C, 2007)	0.76
"5 microg/mL) (Li/DVP) (for 3-6 weeks) in four double-blind, placebo-controlled studies according to a predetermined dosing schedule."	( Quetiapine in the treatment of acute mania: target dose for efficacious treatment. Goldberg, JF; Mullen, J; Paulsson, B; Vågerö, M; Vieta, E, 2007)	0.34
" Dose escalation was rapid, with 92% of patients treated with monotherapy and 80% of patients treated with combination therapy reaching doses of 400 mg/day by Day 4, in accordance with protocol-defined dosing guidance."	( Quetiapine in the treatment of acute mania: target dose for efficacious treatment. Goldberg, JF; Mullen, J; Paulsson, B; Vågerö, M; Vieta, E, 2007)	0.34
" The steady-state plasma concentrations of AEDs at the experimental dosage were coincided with the range of clinical therapeutic concentrations."	( [Experimental study on the possibility of brain damage induced by chronic treatment with phenobarbital, clonazepam, valproic acid and topiramate in immature rats]. Cai, FC; Zhang, XP; Zhu, HX, 2007)	0.55
"Valproic acid deserves further study for the treatment of CNS tumors given its high CSF penetration after oral dosing coupled with the anti-tumor activity observed in preclinical studies."	( Plasma and cerebrospinal fluid pharmacokinetics of valproic acid after oral administration in non-human primates. Berg, SL; Blaney, SM; Gibson, B; McGuffey, L; Ou, CN; Stapleton, SL; Thompson, PA, 2008)	2.04
"These findings support that divalproex ER is an efficacious and well-tolerated pharmacologic agent for BPD, with the additional advantage of single daily dosing at bedtime."	( An open-label trial of divalproex extended-release in the treatment of borderline personality disorder. Baker, B; Braun, A; Chaplin, W; Hollander, E; Simeon, D, 2007)	0.34
" His divalproex sodium dosage was increased, and he was released from the emergency department only to return 4 days later with recurring seizures."	( Acute seizures in a patient receiving divalproex sodium after starting ertapenem therapy. Lunde, JL; Nelson, RE; Storandt, HF, 2007)	0.34
" Lamotrigine was given for 12 weeks, with a target dosage of 200 mg/d."	( Effect of open-label lamotrigine as monotherapy and adjunctive therapy on the self-assessed cognitive function scores of patients with bipolar I disorder. Graham, J; Kaye, NS; Nanry, K; Roberts, J; Thompson, T, 2007)	0.34
" It included (1) the drugs used for the treatment, (2) their dosage, and (3) the dosage and the schedule of adrenocorticotropic hormone therapy."	( Current treatment of West syndrome in Japan. Ito, M; Okumura, A; Ozawa, H; Tsuji, T; Watanabe, K, 2007)	0.34
" More certainly, they minimise concentration-related adverse effects, and the dosing flexibility and consistency of plasma concentrations may simplify the management of antiepileptic drug therapy."	( Extended-release formulations for the treatment of epilepsy. Bialer, M, 2007)	0.34
" We report the utility of a dosing algorithm designed to maintain stable trough lamotrigine (LTG) concentrations during conversion from valproate (VPA) to LTG monotherapy in adolescents aged 16-20 years."	( Conversion to lamotrigine monotherapy from valproate monotherapy in older adolescent patients with epilepsy. Baumann, RJ; Fakhoury, TA; Hammer, AE; Kustra, RP; Messenheimer, JA; Vuong, A, 2007)	0.34
" Quetiapine and valproic acid plasma concentration-time data over a 12-h steady-state dosing interval were used to determine C(max), T(max), C(min), area under the plasma concentration-time curve (AUC(tau)), and oral clearance (CL/F)."	( Open-label steady-state pharmacokinetic drug interaction study on co-administered quetiapine fumarate and divalproex sodium in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. Davis, PC; DeVane, CL; Ennis, DJ; Figueroa, C; Hamer-Maansson, JE; Smith, MA; Winter, HR, 2007)	0.69
" It will be valuable to facilitate individualized dosage regimens."	( Population pharmacokinetics of valproate in Chinese children with epilepsy. Bai, XR; Jiang, DC; Li, L; Lu, W; Wang, L; Wang, YQ, 2007)	0.34
" Inclusion criteria included residency in a nursing home for at least 2 months, aged 65 years or older, a stable dosing regimen of VPA for at least 4 weeks, VPA concentration, and complete dosing information."	( Population pharmacokinetics of valproic acid concentrations in elderly nursing home residents. Ahn, JE; Birnbaum, AK; Brundage, RC; Conway, JM; Hardie, NA; Leppik, IE, 2007)	0.63
" Fluorescence polarization immunoassay (FPIA) was used to measure the serum concentration of sodium valproate and the results were standardized by dosage and body weight."	( [Effect of UGT1A6 genetic polymorphisms on the metabolism of sodium valproate]. Song, JH; Sun, YP; Tan, L; Wang, Y, 2007)	0.34
" The dosage of sodium valproate for the patients with 552C allele in UGT1A6 should be more than the usual dosage."	( [Effect of UGT1A6 genetic polymorphisms on the metabolism of sodium valproate]. Song, JH; Sun, YP; Tan, L; Wang, Y, 2007)	0.34
" Future prospective studies are necessary to clarify whether the prescribed dosage should be different in young and older patients."	( Age and gender effects on olanzapine and risperidone plasma concentrations in children and adolescents. Aichhorn, W; Hinterhuber, H; Kemmler, G; Marksteiner, J; Stuppaeck, C; Walch, T; Zernig, G, 2007)	0.34
" In either case, the effective dosage of divalproex was lower than that commonly used for epilepsy or mania in elderly patients."	( Report on an open-label prospective study of divalproex sodium for the behavioral and psychological symptoms of dementia as monotherapy and in combination with second-generation antipsychotic medication. Adkison, L; Ahokpossi, C; Forester, B; Hyde, J; Perez, R; Sribney, W; Vanelli, M, 2007)	0.34
"The authors report an Indian adult female patient with a history of generalized tonic clonic seizures who developed severe features of phenytoin (DPH) toxicity on therapeutic dosage of this antiepileptic drug."	( Severe phenytoin toxicity in a CYP2C9*3*3 homozygous mutant from India. Chandrasekaran, A; Chanolean, S; Narayan, SK; Ramasamy, K, )	0.13
" Recent clinical trials investigate new dosing schedules, routes of administration, and combination regimens."	( Current status of epigenetic treatment in myelodysplastic syndromes. Kuendgen, A; Lübbert, M, 2008)	0.35
" Sodium valproate was administered at the dosage of 10-30 mg/kg/d."	( [Influence of age, body weight and dose on sodium valproate plasma concentrations in children with epilepsy]. Jiang, Z; Liao, HM; Peng, QL; Tang, JW; Zhang, J, 2008)	0.35
" The subjects had 11 plasma samples drawn over a dosing interval on days 1, 15, and 30."	( Effects of minocycline and valproic acid coadministration on atazanavir plasma concentrations in human immunodeficiency virus-infected adults receiving atazanavir-ritonavir. Cruttenden, K; DiCenzo, R; Gelbard, H; Hochreiter, J; Mariuz, P; Peterson, DR; Rezk, NL; Schifitto, G, 2008)	0.64
" Because this was not a multiple-dose study, however, direct comparisons in chronic dosing were not possible."	( Bioequivalence studies of a new valproic acid delayed-release capsule and divalproex sodium delayed-release tablet. Fang, Q; Garikipati, V; Toops, DS, 2008)	0.63
" This guideline applies to the acute ingestion and acute-on-chronic ingestion of immediate-release and extended-release dosage forms of valproic acid, divalproex, and valproate sodium alone."	( Valproic acid poisoning: an evidence-based consensus guideline for out-of-hospital management. Booze, LL; Caravati, EM; Christianson, G; Chyka, PA; Cobaugh, DJ; Erdman, AR; Manoguerra, AS; Nelson, LS; Scharman, EJ; Troutman, WG; Woolf, AD, 2008)	1.99
" Five months prior to the development of neutropenia (defined as ANC <1800 cells/microL), the patient's DVPX dosage was decreased by 250 mg to 1250 mg every morning and 1500 mg every evening."	( Delayed-onset neutropenia with divalproex sodium. Deal, E; Lurk, JT; Stoner, SC, 2008)	0.35
" Four patients experienced relapse with a decreased dosage of valproate."	( Effective prophylactic therapy for cyclic vomiting syndrome in children using valproate. Amakata, K; Fujii, Y; Hikita, T; Kaga, F; Kaneko, S; Kodama, H; Nakamoto, N; Ogita, K; Yanagawa, Y, 2009)	0.35
" The isobolographic analysis for parallel and nonparallel dose-response effects was used in the mouse maximal electroshock seizure (MES) model for evaluation of pharmacodynamic interaction."	( Isobolographic characterization of interactions of retigabine with carbamazepine, lamotrigine, and valproate in the mouse maximal electroshock-induced seizure model. Czuczwar, SJ; Luszczki, JJ; Raszewski, G; Wu, JZ, 2009)	0.35
"The objective of the study was to examine the negative impact of valproates on haemostasis and peripheral blood count in children and to analyse whether these disturbances were dependent on the dosage of valproates and drug level in blood."	( [Impact of valproates on haemostasis and blood cell count in children]. Igrutinović, Z; Marković, S; Obradović, S; Vuletić, B, )	0.13
" These disturbances are in correlation with the dosage and the level of the medicine in blood."	( [Impact of valproates on haemostasis and blood cell count in children]. Igrutinović, Z; Marković, S; Obradović, S; Vuletić, B, )	0.13
" Drug dosage and blood drug level are correlated with their negative impact on haemostasis parameters."	( [Impact of valproates on haemostasis and blood cell count in children]. Igrutinović, Z; Marković, S; Obradović, S; Vuletić, B, )	0.13
" Frequent monitoring of serum levels to support dosing decisions is important to inform better clinical decision making, especially when a loading strategy is used."	( Mood stabilizer loading versus titration in acute mania: audit of clinical practice. Fraser, A; Robinson, G; Wheeler, A, 2008)	0.35
" Significant reduction in lithium dosing was observed among individuals aged 50 and older and among individuals 60 and older for valproate."	( Prescription patterns of psychotropic medications in elderly compared with younger participants who achieved a "recovered" status in the systematic treatment enhancement program for bipolar disorder. Al Jurdi, RK; Gyulai, L; Marangell, LB; Martinez, M; Petersen, NJ; Sajatovic, M, 2008)	0.35
" Divalproex sodium extended-release was initiated at 500 mg/day for 15 days then increased to 1000 mg daily, with subsequent adjustments permitted within a dosing range of 250-1000 mg daily."	( Divalproex sodium extended-release for the prophylaxis of migraine headache in adolescents: results of a stand-alone, long-term open-label safety study. Abi-Saab, WM; Apostol, G; Fugate, JM; Laforet, GA; Lewis, DW; Robieson, WZ; Saltarelli, MD, 2009)	0.35
" Divalproex ER was initiated on day 1 at 20 mg/kg per day q AM and was titrated to clinical effect on days 3, 7, and 10, not to exceed a maximum dosage of 35 mg/kg per day."	( Divalproex ER combined with olanzapine or risperidone for treatment of acute exacerbations of schizophrenia. Abi-Saab, W; Baker, J; Casey, DE; Daniel, DG; Greco, N; Kane, JM; Redden, L; Saltarelli, M; Tamminga, C; Tran-Johnson, T; Wozniak, P, 2009)	0.35
"Total body weight, daily dose of valproate and concomitant therapy with PB are factors that significantly influence VPA kinetic disposition and they should be considered in programming dosage regimens for this antiepileptic drug in the pediatric population."	( Population pharmacokinetics of valproate in Mexican children with epilepsy. Correa, T; Rodríguez, I; Romano, S, 2008)	0.35
" VPA was also combined with low dosed interferon-alpha (IFN-alpha) and the efficacy of the combination therapy, as opposed to VPA monotherapy, was compared."	( Valproic acid blocks adhesion of renal cell carcinoma cells to endothelium and extracellular matrix. Blaheta, RA; Hintereder, G; Hudak, L; Jonas, D; Jones, J; Juengel, E; Mickuckyte, A; Wedel, S, 2009)	1.8
" The inhibition of the target in non-tumour peripheral blood cells (taken as a potential surrogate marker) was measured periodically, and valproate dosing adjusted with the attempt to reach a measurable inhibition."	( A phase I-II study of the histone deacetylase inhibitor valproic acid plus chemoimmunotherapy in patients with advanced melanoma. Ballarini, M; Contegno, F; Croci, D; Goldhirsch, A; Minucci, S; Munzone, E; Nolè, F; Pelicci, PG; Rocca, A; Salmaggi, A; Testori, A; Tosti, G, 2009)	0.6
" The increased dosage required may have been due to rapid intestinal transit time or to bypass of the left colon."	( The effect of constipation on valproic acid dosage in a 17-year-old. Madan Cohen, JE; Moshe, SL, 2009)	0.64
" For each class, the dosing scheme and practical issues related to administration are described, based on evidence when available in the literature."	( [Drugs for status epilepticus treatment]. Mazoit, JX; Navarro, V, 2009)	0.35
" We report here that, while dietary supplementation with high VPA dosage slows down motor neuron death, as assessed by measurement of a specific marker for cholinergic neurons in the spinal cord, it has no significant effect on lifespan."	( Long-term dietary administration of valproic acid does not affect, while retinoic acid decreases, the lifespan of G93A mice, a model for amyotrophic lateral sclerosis. Bonamassa, B; Canistro, D; Contestabile, A; Crochemore, C; Paolini, M; Pena-Altamira, E; Virgili, M, 2009)	0.63
"015), time since dosing (p=0."	( Hyperammonemia following intravenous valproate loading. Beasley, MT; Cofield, S; DeWolfe, JL; Faught, E; Knowlton, RC; Limdi, NA, 2009)	0.35
"In this 12 week, randomized, double-blind pilot study, 60 patients diagnosed with acute mania (DSM-IV) and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexibly dosed oxcarbazepine (1,000-2,400 mg/day) or divalproex (750-2,000 mg/day)."	( Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study. Chopra, D; Gupta, NK; Kakkar, AK; Kataria, D; Rehan, HS; Unni, KE, 2009)	0.35
" These findings showed that with a much lower dosage of the drugs, which is suggested in texts can lead to an appropriate blood level of CBZ and VPA for controlling the epileptic seizures."	( An experimental design for finding of minimum dosage of carbamazepine and valproate in preventing of seizure attacks. Nobahar, M; Samaei, A; Vafaei, AA, 2009)	0.35
"To characterize the interaction between tiagabine (TGB) and valproate (VPA)--two antiepileptic drugs in the mouse pentylenetetrazole (PTZ)-induced clonic seizure model, type I isobolographic analysis for non-parallel dose-response relationship curves (DRRCs) was used."	( Interaction of tiagabine with valproate in the mouse pentylenetetrazole-induced seizure model: an isobolographic analysis for non-parallel dose-response relationship curves. Krzyzanowski, M; Luszczki, JJ; Swiader, MJ, 2009)	0.35
" The evaluation of time-course and dose-response relationships for imperatorin, osthole and valproate in the maximal electroshock seizure test revealed that the compounds produced a clear-cut antielectroshock action in mice and the experimentally derived ED(50) values for imperatorin ranged between 167 and 290 mg/kg, those for osthole ranged from 253 to 639 mg/kg, whereas the ED(50) values for valproate ranged from 189 to 255 mg/kg."	( Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate in the maximal electroshock seizure and chimney tests in mice: a comparative study. Andres-Mach, M; Cisowski, W; Czuczwar, SJ; Glensk, M; Glowniak, K; Luszczki, JJ; Wojda, E, 2009)	0.35
" The specificity of acute kidney injury (AKI) biomarkers, iNOS, and nitrotyrosine was evaluated by dosing rats with valproic acid (VPA)."	( Differences in immunolocalization of Kim-1, RPA-1, and RPA-2 in kidneys of gentamicin-, cisplatin-, and valproic acid-treated rats: potential role of iNOS and nitrotyrosine. Bonventre, JV; Brown, RP; Espandiari, P; Goering, PL; Hanig, JP; Keenan, J; Kilty, CG; Sadrieh, N; Shaw, M; Vaidya, VS; Zhang, J, 2009)	0.78
"In Porsteinsson 2001, although the physicians having direct responsibility for patient care were blinded, a non-blinded physician, who had no direct contact with these physicians, adjusted divalproex sodium dosage on the basis of reports from blinded raters and from confidential laboratory reports."	( Valproate preparations for agitation in dementia. Lonergan, E; Luxenberg, J, 2009)	0.35
" Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3s stimulus duration) delivered via ocular electrodes and isobolographic analysis for parallel and non-parallel dose-response effects was used to characterize the consequent anticonvulsant interactions between the various drug combinations."	( Isobolographic characterization of interactions of levetiracetam with the various antiepileptic drugs in the mouse 6 Hz psychomotor seizure model. Luszczki, JJ; Patsalos, PN; Wlaz, A; Wojda, E, 2009)	0.35
"In this study 27 patients with focal or generalized epilepsy receiving a single dosage of prolonged-release valproate given in the evening were included."	( Once daily monotherapy with prolonged-release valproate minitablets given in the evening--a chronopharmacological study. Fraunberger, B; Graf, W; Kerling, F; Pauli, E; Stefan, H; Yang, T, 2009)	0.35
" In the case of the 24-hour serum profile, when the daily dosage was weight-correlated no values for the normal dosage range (18 - 24 mg/kg body weight) gave values that exceeded or fell below the so-called therapeutic serum level range (50 - 100 mg/l)."	( Once daily monotherapy with prolonged-release valproate minitablets given in the evening--a chronopharmacological study. Fraunberger, B; Graf, W; Kerling, F; Pauli, E; Stefan, H; Yang, T, 2009)	0.35
"Therefore, in the case of adults and young adults, therapy with valproate prolonged-release at a dose rate of 24 mg/kg preparation given as a single dosage in the evening will be sufficient for seizure control in most patients."	( Once daily monotherapy with prolonged-release valproate minitablets given in the evening--a chronopharmacological study. Fraunberger, B; Graf, W; Kerling, F; Pauli, E; Stefan, H; Yang, T, 2009)	0.35
" No stereoselective pharmacokinetics was observed following intraperitoneal dosing of racemic-VCU to rats."	( Evaluation of stereoselective anticonvulsant, teratogenic, and pharmacokinetic profile of valnoctylurea (capuride): a chiral stereoisomer of valproic acid urea derivative. Bialer, M; Finnell, RH; Schurig, V; Shimshoni, JA; Wlodarczyk, B; Yagen, B, 2010)	0.56
" In each period, subjects received single oral doses of 500-mg MgV solution, suspension, and enteric-coated tablet formulations, with a 7-day washout period between each dosing period."	( A single-dose, three-period, six-sequence crossover study comparing the bioavailability of solution, suspension, and enteric-coated tablets of magnesium valproate in healthy Mexican volunteers under fasting conditions. Angeles-Moreno, AP; Contreras-Zavala, L; Marcelín-Jiménez, G; Morales-Martínez, M; Rivera-Espinosa, L, 2009)	0.35
" dosed on day 8 with VPA 400mg/kg or TSA (16 mg/kg)."	( VPA-related axial skeletal defects and apoptosis: a proposed event cascade. Broccia, ML; Di Renzo, F; Giavini, E; Menegola, E, 2010)	0.36
" Children whose aggressive behavior persisted at the conclusion of the lead-in phase were randomly assigned to receive double-blind, flexibly dosed divalproex or a placebo adjunctive to stimulant for 8 weeks."	( Adjunctive divalproex versus placebo for children with ADHD and aggression refractory to stimulant monotherapy. Blader, JC; Jensen, PS; Kafantaris, V; Pliszka, SR; Schooler, NR, 2009)	0.35
" We predict that excursions beyond the conventional recommended VPA plasma concentration range will commonly occur with high total mg daily doses (>or=2000 mg) of enteric-coated divalproex, if dosed once-daily, potentially producing clinical toxicity."	( Once-daily dosing is appropriate for extended-release divalproex over a wide dose range, but not for enteric-coated, delayed-release divalproex: evidence via computer simulations and implications for epilepsy therapy. Dutta, S; Liu, W; Reed, RC, 2009)	0.35
" TDM requests, interpretation and dosage adjustment recommendations were mainly responsible by residents."	( Effect of pharmacist participation in the health care team on therapeutic drug monitoring utilization for antiepileptic drugs. Faroongsarng, D; Kaewpibal, P; Ratanajamit, C; Setthawacharavanich, S, 2009)	0.35
" These changes tended to parallel prescribing trends in the wider community, except for valproate, whose prescribing in the overall community increased as its prescribing, and its dosage prescribed, decreased in pregnancy."	( Changing patterns of antiepileptic drug use in pregnant Australian women. Eadie, MJ; Graham, J; Hitchcock, AA; Hollingworth, S; Lander, CM; O'Brien, TJ; Vajda, FJ, 2010)	0.36
"Sparse information on dose-response characteristics for initial antiepileptic drug monotherapy in children with idiopathic generalized epilepsy (IGE) is available."	( Valproate in children with newly diagnosed idiopathic generalized epilepsy. Glauser, TA; Holland, KD; Monahan, S; Morita, D; Vartzelis, G, 2010)	0.36
"We evaluated the cross-sectional relationship of duration and dosage of valproate monotherapy on bone mineral density (BMD) in adult patients with epilepsy."	( Effect of long-term valproate monotherapy on bone mineral density in adults with epilepsy. Antoniou, A; Armeni, E; Boufidou, F; Evangelopoulos, EM; Lambrinoudaki, I; Triantafyllou, N; Tsivgoulis, G, 2010)	0.36
" Duration and dosage of valproate monotherapy did not correlate with BMD."	( Effect of long-term valproate monotherapy on bone mineral density in adults with epilepsy. Antoniou, A; Armeni, E; Boufidou, F; Evangelopoulos, EM; Lambrinoudaki, I; Triantafyllou, N; Tsivgoulis, G, 2010)	0.36
"To review our clinical experience and determine if there are appropriate signs and symptoms to consider POLG sequencing prior to valproic acid (VPA) dosing in patients with seizures."	( POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders. Bao, X; Koenig, MK; Lee, IC; Naviaux, RK; Saneto, RP; Weng, SW; Wong, LJ, 2010)	0.8
"Our cases underscore several important findings: POLG mutations have been observed in every ethnic group studied to date; early predominance of epileptiform discharges over the occipital region is common in POLG-induced epilepsy; the EEG and MRI findings varying between patients and stages of the disease; and VPA dosing at any stage of Alpers-Huttenlocher syndrome can precipitate liver failure."	( POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders. Bao, X; Koenig, MK; Lee, IC; Naviaux, RK; Saneto, RP; Weng, SW; Wong, LJ, 2010)	0.6
" Mean dosage was 687 (SD = 234) mg/day (min 400, max 1,500 mg/day)."	( Adjunctive valproate in panic disorder patients with comorbid bipolar disorder or otherwise resistant to standard antidepressants: a 3-year "open" follow-up study. Akiskal, HS; Frare, F; Perugi, G; Toni, C; Tusini, G; Vannucchi, G, 2010)	0.36
" This once-a-day dosing formulation may increase compliance."	( Valproate semisodium ER for migraine and cluster headache prophylaxis. Lovell, BV; Marmura, MJ, 2010)	0.36
" The daily divalproex ER dosage was initiated at 20 mg/kg."	( A randomized, placebo-controlled, multicenter study of divalproex sodium extended-release in the acute treatment of mania. Bowden, CL; Collins, M; Hirschfeld, RM; Vigna, NV; Wozniak, P, 2010)	0.36
"The aim of this study was to characterize the anticonvulsant effects of stiripentol (STP) in combination with clobazam [CLB], and valproate [VPA]) in the mouse maximal electroshock (MES)-induced seizure model using the type I isobolographic analysis for parallel and non-parallel dose-response relationship curves (DRRCs)."	( Interactions of stiripentol with clobazam and valproate in the mouse maximal electroshock-induced seizure model. Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N; Trojnar, MK, 2010)	0.36
" The propranolol dosage was adjusted to 2 mg/kg/day and the sodium valproate dosage to 15 mg/kg/day, after the first follow-up visit."	( A randomized trial of propranolol versus sodium valproate for the prophylaxis of migraine in pediatric patients. Bidabadi, E; Mashouf, M, 2010)	0.36
" Dose-response studies revealed that systemic administration of 400 mg/kg (i."	( Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats. Dash, PK; Grill, RJ; Moore, AN; Orsi, SA; Pati, S; Zhang, M; Zhao, J, 2010)	0.36
" Patients treated with lithium or divalproex (ongoing or assigned at screening) were randomized to receive quetiapine (dosed up to 400 mg/d over 7 days, followed by 300 to 800 mg/d flexible dosing until study end) or placebo."	( A double-blind, placebo-controlled study with quetiapine as adjunct therapy with lithium or divalproex in bipolar I patients with coexisting alcohol dependence. Brown, ES; Calabrese, JR; Kotz, M; Pettinati, HM; Raines, S; Stedman, M, 2010)	0.36
" Dosing and plasma levels of levetiracetam and concomitant antiepileptic drugs were reviewed retrospectively."	( Age and comedications influence levetiracetam pharmacokinetics in children. Dahlin, MG; Ohman, I; Wide, K, 2010)	0.36
" The hydralazine dose was given according with the acetylator phenotype, and valproate was dosed at 30 mg/kg/day."	( Hydralazine and magnesium valproate as epigenetic treatment for myelodysplastic syndrome. Preliminary results of a phase-II trial. Arias-Bofill, D; Candelaria, M; Cervera, E; de la Cruz-Hernández, E; Dueñas-Gonzalez, A; González-Fierro, A; Herrera, A; Labardini, J; Pérez-Cárdenas, E; Taja-Chayeb, L; Trejo-Becerril, C; Vidal, S, 2011)	0.37
" Improvement was noted after the drug dosage was reduced."	( Respiratory alkalosis and metabolic acidosis in a child treated with sulthiame. Garty, BZ; Hoffer, V; Scheuerman, O; Tirosh, I; Weissbach, A, 2010)	0.36
"The derived models describe well VPA clearance in terms of characteristics of Serbian pediatric and adult epileptic patients, offering a basis for rational individualization of VPA dosage regimens."	( Factors influencing valproate pharmacokinetics in children and adults. Jankovic, S; Jankovic, SM; Milovanovic, JR, 2010)	0.36
"Many investigators agree that appropriate rational utilization of therapeutic drug monitoring (TDM) with Bayesian feedback dosage adjustment facilitates epilepsy treatment with carbamazepine (CBZ) and/or valproate (VPA) by increasing the seizure control and safety, as well as by reducing treatment costs."	( Predictability of individualized dosage regimens of carbamazepine and valproate mono- and combination therapy. Andreeva, OV; Bondareva, IB; Bondareva, KI; Jelliffe, RW, 2011)	0.37
"Our validation results suggest good predictive performance of the population models developed earlier, and quite acceptable predictions of future AED serum levels for individualized dosage regimens of CBZ and VPA therapy in real clinical settings."	( Predictability of individualized dosage regimens of carbamazepine and valproate mono- and combination therapy. Andreeva, OV; Bondareva, IB; Bondareva, KI; Jelliffe, RW, 2011)	0.37
" Here we evaluated the dosage effects of HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) in a series of human leukaemia cell lines."	( Epigenetic modulation of gene expression of human leukemia cell lines - induction of cell death and senescence. Elknerova, K; Lacinova, Z; Marinov, I; Myslivcova, D; Stöckbauer, P; Uherkova, L, 2011)	0.59
" The patients' characteristics and pharmacokinetic parameters were compared between the 2 dosage groups using independent t test or χ² test where appropriate."	( The impact of dosage of sustained-release formulation on valproate clearance and plasma concentration in psychiatric patients: analysis based on routine therapeutic drug monitoring data. Chamchitchun, S; Panomvana, D; Silpakit, O; Sriboonruang, T, 2011)	0.37
" These findings provide useful information to adjust the VPA dosage to achieve optimal therapeutic efficacy in epileptic infants."	( Empirical approach for improved estimation of unbound serum concentrations of valproic acid in epileptic infants by considering their physical development. Aiba, T; Kurosaki, Y; Matsunaga, H; Ohtsuka, Y; Sato, T; Sendo, T; Ueshima, S, 2011)	0.6
" Data from a full pharmacokinetic curve (multiple blood samples during a dosing interval) showed that the free fraction of valproic acid was >60%."	( High unbound fraction of valproic acid in a hypoalbuminemic critically ill patient on renal replacement therapy. de Maat, MM; Edelbroek, PM; van Leeuwen, HJ, 2011)	0.88
" In the process of introduction and increase in the dosage of VPA, an aggravation of epileptic discharges, especially a dramatic increase in diffuse spike-waves during sleep, was observed."	( [Aggravation of epilepsy by valproate sodium in a child with cryptogenic localization-related epilepsy]. Ohtsuka, Y; Watanabe, K; Watanabe, Y, 2011)	0.37
" Adenomyosis was induced in 55 female ICR mice neonatally dosed with tamoxifen, while another 8 (group C) were dosed with solvent only."	( The retardation of myometrial infiltration, reduction of uterine contractility, and alleviation of generalized hyperalgesia in mice with induced adenomyosis by levo-tetrahydropalmatine (l-THP) and andrographolide. Carter, AV; Guo, SW; Mao, X; Wang, Y; Zhen, X, 2011)	0.37
"Intermittent drug dosing intervals are usually initially guided by the terminal pharmacokinetic half life and are dependent on drug formulation."	( Intermittent drug dosing intervals guided by the operational multiple dosing half lives for predictable plasma accumulation and fluctuation. Benet, LZ; Grover, A, 2011)	0.37
" 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
"Eight patients with low-grade NETs (carcinoid and pancreatic) were treated with 500 mg of oral VPA twice a day with dosing adjusted to maintain a goal VPA level between 50 and 100 μg/mL."	( A pilot phase II study of valproic acid for treatment of low-grade neuroendocrine carcinoma. Chen, H; Eickhoff, J; Holen, KD; Jaskula-Sztul, R; Loconte, NK; Lubner, SJ; Mohammed, TA; Mulkerin, D; Schelman, WR, 2011)	0.67
" In this study, we evaluated the effect of valproic acid (VPA) in ICR mice with adenomyosis, induced by neonatal dosing with tamoxifen."	( Valproic acid alleviates generalized hyperalgesia in mice with induced adenomyosis. Guo, SW; Liu, X, 2011)	2.07
" Neurologists had progressively prescribed valproate less frequently and in lower dosage than other classes of practitioner over the 10-year study period, with a parallel decrease in occurrence of fetal malformations in pregnancies referred to the Register."	( The prescribing of antiepileptic drugs for pregnant Australian women. Eadie, MJ; Graham, J; Hitchcock, AA; Hollingworth, S; Horgan, D; Lander, CM; O'Brien, TJ; Roten, A; Vajda, FJ, 2012)	0.38
"Valproic acid is widely used in the treatment of behavioral disturbances in patients with dementia; however, there is uncertainty about its dosing and studies have reported mixed findings."	( Valproic acid in dementia: does an optimal dose exist? Dolder, CR; McKinsey, J; Nealy, KL, 2012)	3.26
"This study deals with the development of an oral controlled-release dosage form of a highly water-soluble antiepileptic drug."	( Controlled release of a highly hydrophilic API from lipid microspheres obtained by prilling: analysis of drug and water diffusion processes with X-ray-based methods. Daste, G; Faivre, V; Gueutin, C; Lesieur, S; Mancini, L; Ollivon, M; Pivette, P, 2012)	0.38
" Area under the concentration-time curve during a 12-hour dosing interval at steady state (AUC(τ,ss)) and maximum steady-state plasma drug concentration (C(max,ss)) were measured for each drug alone and together and tested for equivalence."	( No pharmacokinetic interaction between lacosamide and valproic acid in healthy volunteers. Bonn, R; Cawello, W, 2012)	0.63
"Valproic acid (VPA) dosing strategies used in recent clinical trials in patients with spinal muscular atrophy (SMA) have utilized a paradigm of monitoring trough levels to estimate drug exposure with subsequent dose titration."	( Population pharmacokinetics of valproic acid in pediatric patients with epilepsy: considerations for dosing spinal muscular atrophy patients. Barrett, JS; Jayaraman, B; Swoboda, KJ; Williams, JH, 2012)	2.11
" Early administration of VPA as an adjunct to temozolomide chemotherapy may have its merits, but the optimal dosing schedule and target serum level require further investigation."	( Effect of valproic acid on the outcome of glioblastoma multiforme. Chen, PY; Chen, SM; Huang, YC; Lee, ST; Lu, YJ; Tsai, CN; Tsai, HC; Wei, KC, 2012)	0.78
" The dosage was adjusted according to the level of pain control and side-effects."	( Use of single- and multi-drug regimens in the management of classic (idiopathic) trigeminal neuralgia: an 11-year experience at a single Sri Lankan institution. Ariyawardana, A; Pallegama, R; Ranasinghe, A; Sitheeque, M, 2012)	0.38
" We increased the LTG dosage every two weeks in accordance with usage recommendations."	( [Lamotrigine add-on therapy for childhood-onset refractory epilepsy: comparison of the efficacy between 3 months and 6 months after initiation]. Endoh, F; Kobayashi, K; Ohtsuka, Y; Watanabe, K; Yoshinaga, H, 2011)	0.37
" Propensity-stratified and propensity-weighted models as well as analyses controlling for site of care and medication dosage revealed similar patterns."	( Risk of mortality among individual antipsychotics in patients with dementia. Blow, FC; Chiang, C; Cunningham, F; Kales, HC; Kim, HM; Schneider, LS; Seyfried, LS; Valenstein, M; Zivin, K, 2012)	0.38
" Concomitant use of drugs metabolized by CYP2D6 may require dosage adjustment."	( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012)	0.38
"This audit was conducted on acute psychiatric in-patient wards with the aim of establishing if valproate prescribing in acute mania followed evidence-based guidelines with particular emphasis on formulations used and whether accelerated valproate dosing was employed."	( Valproate in acute mania: is our practice evidence based? Macritchie, K; Mead, A; Vasudev, K; Young, AH, 2012)	0.38
"Accelerated valproate dosing was not common practice, which may have resulted in suboptimal efficacy, probably leading to combination treatment."	( Valproate in acute mania: is our practice evidence based? Macritchie, K; Mead, A; Vasudev, K; Young, AH, 2012)	0.38
"This study highlights the need for adequate initial dosing and dose increments when treating manic patients and suggests current practice is not evidence-based."	( Valproate in acute mania: is our practice evidence based? Macritchie, K; Mead, A; Vasudev, K; Young, AH, 2012)	0.38
" Moreover, a VPA dose-response curve was performed on PBMC obtained from healthy controls, demonstrating an increase of acetyl-histone H3 content."	( Valproate induces epigenetic modifications in lymphomonocytes from epileptic patients. Conti, E; Difrancesco, JC; Ferrarese, C; Galimberti, G; Riva, C; Rodriguez-Menendez, V; Ruffmann, C; Tremolizzo, L, 2012)	0.38
" There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups."	( Topiramate increases the risk of valproic acid-induced encephalopathy. Chu, K; Jung, KH; Kim, DW; Lee, SK; Lee, ST; Moon, HJ; Noh, Y, 2013)	0.67
" An additional potential benefit would be significantly reduced dosing while achieving high brain concentrations."	( Chronic central administration of valproic acid: Increased pro-survival phospho-proteins and growth cone associated proteins with no behavioral pathology. Bates, RC; Stevens, KE; Stith, BJ, 2012)	0.66
"These analyses confirm the effectiveness of ziprasidone (80-160mg/day) in preventing relapses in subjects with bipolar disorder, with the 120mg/day dosage appearing to have the highest relapse prevention rate."	( Characterizing relapse prevention in bipolar disorder with adjunctive ziprasidone: clinical and methodological implications. Bowden, CL; Gundapaneni, BK; Karayal, ON; O'Gorman, C; Schwartz, JH, 2013)	0.39
" In addition, there appeared to be a dose-response relationship between stroke risk and PHT prescriptions."	( Comparative stroke risk of antiepileptic drugs in patients with epilepsy. Hsieh, CY; Lai, EC; Lin, SJ; Yang, YH, 2013)	0.39
" Treatment with valproic acid (VPA), a histone deacetylase inhibitor, at 3 dosing regimens (300mg/kg at D2-9PP; 100mg/kg at D2-4PP, 200mg/kg at D5-7PP, 300mg/kg at D8-9PP; 100mg/kg at D2-5PP, 200mg/kg at D6-9PP) prior to daily separation reversed such a decrease in fear-potentiated startle."	( Neonatal isolation decreases cued fear conditioning and frontal cortical histone 3 lysine 9 methylation in adult female rats. Chen, LH; Cheng, LY; Cherng, CG; Kao, GS; Su, CC; Tzeng, WY; Wang, CY; Yu, L, 2012)	0.72
" Clinical variables are useful to model a dosing nomogram for serum clozapine levels."	( Clinical predictors of serum clozapine levels in patients with treatment-resistant schizophrenia. Jacob, KS; Jacob, M; Kuruvilla, A; Poonkuzhali, B; Rajkumar, AP, 2013)	0.39
" These technologies extend the dosing interval such that dosing frequency can be minimized, which may improve patient adherence."	( Extended-release antiepileptic drugs: a comparison of pharmacokinetic parameters relative to original immediate-release formulations. Hovinga, CA; Leppik, IE, 2013)	0.39
" Mean PGB dosage was 279 mg/day."	( Effect of pregabalin add-on treatment on seizure control, quality of life, and anxiety in patients with brain tumour-related epilepsy: a pilot study. Carapella, CM; Dinapoli, L; Fabi, A; Maschio, M; Pace, A; Pompili, A; Sperati, F; Vidiri, A, 2012)	0.38
"Children with refractory epilepsy who suffered from severe liver function impairment during valproic acid (VPA) treatment at routine dosage were studied."	( [Valproic acid-induced idiosyncratic liver injury in 4 cases]. Bao, XH; Jiang, YW; Liu, CT; Qin, J; Wu, XP; Xiong, H; Zhang, YH; Zhao, H, 2012)	1.51
" They responded well to the reduction in dosage or to withdrawal of the apparent causing agent."	( [Medication-related oculogyric crises: a description of four cases and a review of the literature]. Campistol, J; Darling, A; Perez-Duenas, B; Poo, P, 2013)	0.39
" Oral dosing of mice results in absorption of intact prodrug with slow systemic hydrolysis yielding higher plasma levels of LY2334737 than gemcitabine and prolonged gemcitabine exposure."	( Efficacy of low-dose oral metronomic dosing of the prodrug of gemcitabine, LY2334737, in human tumor xenografts. Dantzig, AH; Donoho, GP; Durland-Busbice, S; Perkins, EJ; Pratt, SE; Shepard, RL; Starling, JJ; Wickremsinhe, ER, 2013)	0.39
" We report a 17-year-old man with epilepsy and Down's syndrome who experienced tremor during the treatment with a low dosage of sodium valproate."	( Sodium valproate induced tremor in a patient with epilepsy and Down's syndrome. De Sarro, G; Gallelli, L; Loizzo, S; Russo, E; Siniscalchi, A; Tiziana, A, 2013)	0.39
" Physiologic and laboratory parameters were closely measured and the pigs divided into four groups: sham, control (injury protocol), VPA dosing before cross-clamp (VPA-B), and VPA dosing after cross-clamp (VPA-A)."	( Beneficial effects of histone deacetylase inhibition with severe hemorrhage and ischemia-reperfusion injury. Alam, H; Causey, MW; Hempel, J; Hoffer, Z; Jin, G; Martin, M; Miller, S; Stallings, JD, 2013)	0.39
" Earlier administration (VPA-B) was significantly less effective compared with dosing after initial hemorrhage control."	( Beneficial effects of histone deacetylase inhibition with severe hemorrhage and ischemia-reperfusion injury. Alam, H; Causey, MW; Hempel, J; Hoffer, Z; Jin, G; Martin, M; Miller, S; Stallings, JD, 2013)	0.39
" To define the dose-dependent properties and longevity of the studied effects of valproate, two distinguished dosing regiments were used: bolus (single infusion at a dose of 300 mg/kg) and cumulative (thrice-repeated administration of 100mg/kg performed 30 min apart)."	( Intravenous valproate inhibits ongoing and evoked activity of dura-sensitive thalamic neurons in rats. Berkovich, RR; Lyubashina, OA; Panteleev, SS; Sivachenko, IB; Sokolov, AY, 2013)	0.39
" A cautious dosing of AMI with VPA comedication is advisable, and therapeutic drug monitoring should be performed because this combination may lead to a remarkable increase of AMI and NOR serum levels."	( Interaction of valproic acid and amitriptyline: analysis of therapeutic drug monitoring data under naturalistic conditions. Burger, R; Deckert, J; Hohage, A; Pfuhlmann, B; Unterecker, S, 2013)	0.74
" Fourteen healthy subjects (seven women and seven men) were enrolled, food intake was standardized, blood samples were withdrawn up to 48 h post dosing and VPA plasma concentrations were analyzed by HPLC-UV method."	( Sex related differences on valproic acid pharmacokinetics after oral single dose. Derendorf, H; Fagiolino, P; Ibarra, M; Vázquez, M, 2013)	0.69
" The overall mean maternal valproate dosage taken by women in the Register decreased over the last 5 years of the study period."	( Dose dependence of fetal malformations associated with valproate. Eadie, MJ; Graham, JE; Lander, CM; O'Brien, TJ; Vajda, FJ, 2013)	0.39
" This VPA dosage regimen has been in the past related to a specific pathogenic pathway cascade: (1) VPA in utero exposure, (2) H4 histone hyperacetylation (hAC) at the level of somites, (3) expression of pro-apoptotic factors in somite tissues, (4) apoptosis of somite cells, and (5) axial defects in embryos (abnormal or fused somites) and fetuses (fusions, duplications, respecifications of vertebrae, and/or ribs)."	( Methionine pretreatment enhances the effects of valproate on axial development in a CD1 mouse model. Di Renzo, F; Giavini, E; Menegola, E, 2013)	0.39
" The mean dosage of AED for valproate was 498 mg/day and carbamazepine was 555 mg/day."	( Malformation in index pregnancy in women with epilepsy is not followed by recurrence in subsequent pregnancy. Begum, S; Sarma, SP; Thomas, SV, 2013)	0.39
"Mutations in SHANK3 and large duplications of the region spanning SHANK3 both cause a spectrum of neuropsychiatric disorders, indicating that proper SHANK3 dosage is critical for normal brain function."	( SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties. Breman, AM; Chen, H; Cheung, SW; Han, K; Hao, S; Holder, JL; Kang, H; Lu, H; Lu, HC; Patel, A; Schaaf, CP; Sun, H; Tang, J; Wu, Z; Yu, P; Zoghbi, HY, 2013)	0.39
" Participants were evaluated at baseline and after 12 weeks with: Clinical Global Impression - Severity (CGI-S), Hamilton Scales for depression and anxiety (HAM-D, HAM-A), Social and Occupational Functioning Assessment Scale (SOFAS), borderline personality disorder severity index (BPDSI), Barratt Impulsiveness Scale - version 11 (BIS-11), Modified Overt Aggression Scale (MOAS), Self-Harm Inventory (SHI) and Dosage Record Treatment Emergent Symptom Scale (DOTES)."	( Efficacy of omega-3 fatty acids in the treatment of borderline personality disorder: a study of the association with valproic acid. Bellino, S; Bogetto, F; Bozzatello, P; Rocca, G, 2014)	0.61
" The dosage regimen should be adjusted accordingly to gain a better clinical outcome."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.59
" Delayed dosing did not reduce adhesions."	( Histone deacetylase inhibitors decrease intra-abdominal adhesions with one intraoperative dose by reducing peritoneal fibrin deposition pathways. Cassidy, MR; Gainsbury, ML; Heydrick, S; Sheldon, HK; Sherburne, AC; Stucchi, AF, 2014)	0.4
" A single, intraoperative intervention provides an ideal dosing strategy and indicates an exciting new role for HDACIs in adhesion prevention."	( Histone deacetylase inhibitors decrease intra-abdominal adhesions with one intraoperative dose by reducing peritoneal fibrin deposition pathways. Cassidy, MR; Gainsbury, ML; Heydrick, S; Sheldon, HK; Sherburne, AC; Stucchi, AF, 2014)	0.4
"The LTG population pharmacokinetic model developed in this study may be a reliable method for individualising the LTG dosing regimen in paediatric and young adult patients on combination therapy during therapeutic drug monitoring."	( Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients--nonlinear mixed effects modelling approach. Brzaković, B; Kovačević, SV; Martinović, Ž; Miljković, B; Pokrajac, M; Prostran, M; Vučićević, K, 2014)	0.4
" As a consequence, if a combination of valproic acid with doxepin or venlafaxine is administered, cautious dosing is advisable and TDM should be performed."	( Interaction of valproic acid and the antidepressant drugs doxepin and venlafaxine: analysis of therapeutic drug monitoring data under naturalistic conditions. Deckert, J; Hempel, S; Pfuhlmann, B; Proft, F; Reif, A; Riederer, P; Unterecker, S, 2014)	1.02
" This adverse effect does not display normal dose-response curves and can be lethal in children."	( Evidence for a potential protective effect of carnitine-pantothenic acid co-treatment on valproic acid-induced hepatotoxicity. Felker, D; Johnson, DE; Lynn, A; Wang, S, 2014)	0.62
" The data collected included epilepsy type, seizure frequency, concomitant anti-epileptic drugs, dosage of LTG and LTG serum levels."	( [Clinical efficacy and pharmacokinetics of lamotrigine for childhood-onset intractable epilepsy]. Arakawa, C; Endo, A; Fuchigami, T; Fujita, Y; Imai, Y; Ishii, W; Kohira, R; Momoki, E; Mugishima, H, 2014)	0.4
" In addition, there was a high correlation between the LTG serum levels and the dosage of LTG in each group."	( [Clinical efficacy and pharmacokinetics of lamotrigine for childhood-onset intractable epilepsy]. Arakawa, C; Endo, A; Fuchigami, T; Fujita, Y; Imai, Y; Ishii, W; Kohira, R; Momoki, E; Mugishima, H, 2014)	0.4
"The LTG serum level is predictable based on the dosage of LTG."	( [Clinical efficacy and pharmacokinetics of lamotrigine for childhood-onset intractable epilepsy]. Arakawa, C; Endo, A; Fuchigami, T; Fujita, Y; Imai, Y; Ishii, W; Kohira, R; Momoki, E; Mugishima, H, 2014)	0.4
"The average dosage of LEV was 22."	( Evaluation of levetiracetam and valproic acid as low-dose monotherapies for children with typical benign childhood epilepsy with centrotemporal spikes (BECTS). An, D; Chen, S; Deng, H; Ren, J; Xiao, F; Zhou, D, 2014)	0.69
" The aim of this work was to develop a physiologically based pharmacokinetic model for plasma and tissue/organ prediction in children and adults following intravenous and oral dosing of Valproic acid."	( A physiologically based pharmacokinetic model for Valproic acid in adults and children. Aarons, L; Ogungbenro, K, 2014)	0.85
"73) in VPA-treated patients, but there were no associations with the VPA dosage or the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index."	( Comparison of the metabolic syndrome risk in valproate-treated patients with epilepsy and the general population in Estonia. Eglit, T; Haldre, S; Kõks, S; Lember, M; Rakitin, A, 2014)	0.4
" The blood ammonia level was significantly correlated with the dosage of VPA and the plasma concentration of VPA."	( Risk factors of hyperammonemia in patients with epilepsy under valproic acid therapy. Chang, CC; Chang, WN; Chen, NC; Chuang, YC; Huang, CR; Lin, CH; Lu, CH; Lu, YT; Tseng, YL, 2014)	0.64
"In most dose-response studies, repeated experiments are conducted to determine the EC50 value for a chemical, requiring averaging EC50 estimates from a series of experiments."	( Statistical strategies for averaging EC50 from multiple dose-response experiments. Jiang, X; Kopp-Schneider, A, 2015)	0.42
" We hypothesise that an increase in valproate dosage unmasked clinically silent Parkinson's disease."	( Clinically silent idiopathic Parkinson's disease unmasked by valproate use: a brief report. Athauda, D; Batley, R; Ellis, C, 2015)	0.42
"The present study aimed to establish population pharmacokinetic model for phenobarbital (PB), examining and quantifying the magnitude of PB interactions with other antiepileptic drugs concomitantly used and to demonstrate its use for individualization of PB dosing regimen in adult epileptic patients."	( Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients. Golubović, B; Jovanović, M; Kovačević, SV; Martinović, Ž; Miljković, B; Prostran, M; Vučićević, K, 2015)	0.42
"Developed population PB model may be used in estimating individual CL/F for adult epileptic patients and could be applied for individualizing dosing regimen taking into account dose-dependent effect of concomitantly given VPA."	( Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients. Golubović, B; Jovanović, M; Kovačević, SV; Martinović, Ž; Miljković, B; Prostran, M; Vučićević, K, 2015)	0.42
" Furthermore, the proposed population pharmacokinetic model of VPA can be used to design rational dosage regimens to achieve desirable serum concentrations."	( A population pharmacokinetic model of valproic acid in pediatric patients with epilepsy: a non-linear pharmacokinetic model based on protein-binding saturation. Ding, J; Jiao, Z; Li, X; Lin, W; Miao, L; Wang, C; Wang, Y; Zhao, L; Zhao, Z, 2015)	0.69
" Daily dosing of wild-type mice from postnatal day P17 to P28 resulted in smaller increases in Bdnf and Gdnf expression, normal Cntf expression, and reduced Fgf2 expression (25%)."	( Different effects of valproic acid on photoreceptor loss in Rd1 and Rd10 retinal degeneration mice. Byrd, D; DeLooff, C; Deshpande, M; Guzman, AE; Laux, K; Metcalf, B; Mitton, KP; Mkoyan, K; Sotzen, J; Tran, T; Wallace, A; Zlojutro, P, 2014)	0.72
" For 80 patients treated with sodium valproate, the mean ± SD dosage was 1541."	( Efficacy and safety of valproic acid versus haloperidol in patients with acute agitation: results of a randomized, double-blind, parallel-group trial. Asadollahi, S; Azadbakht, A; Hatamabadi, H; Heidari, K; Mirmohseni, L; Vafaee, R; Yunesian, S, 2015)	0.73
" The symptoms of VHE were not correlated with the dosage and concentration of valproate."	( [Clinical misdiagnosis analysis of valproate encephalopathy]. Chen, X; Su, Z; Wu, Z; Ye, S; Zhu, D; Zhuge, G, 2014)	0.4
" We compared the overall rate of CSEs and intolerable CSEs (ICSEs-CSEs that led to dosage reduction or discontinuation) between different AEDs in both monotherapy and polytherapy."	( Cosmetic side effects of antiepileptic drugs in adults with epilepsy. Buchsbaum, R; Chen, B; Choi, H; Detyniecki, K; Hirsch, LJ; Javed, A; Kato, K; Legge, A; Moeller, J, 2015)	0.42
" Cosmetic side effects leading to dosage change or discontinuation occurred most frequently with pregabalin and valproic acid compared with all other AEDs (13."	( Cosmetic side effects of antiepileptic drugs in adults with epilepsy. Buchsbaum, R; Chen, B; Choi, H; Detyniecki, K; Hirsch, LJ; Javed, A; Kato, K; Legge, A; Moeller, J, 2015)	0.63
"Weight gain and alopecia were the most common patient-reported CSEs in this study, and weight gain was the most likely cosmetic side effect to result in dosage adjustment or medication discontinuation."	( Cosmetic side effects of antiepileptic drugs in adults with epilepsy. Buchsbaum, R; Chen, B; Choi, H; Detyniecki, K; Hirsch, LJ; Javed, A; Kato, K; Legge, A; Moeller, J, 2015)	0.42
"The various oral formulations of valproic acid vary in dosing frequency, form, indication, and cost."	( Which oral valproic acid formulation is best for my patient? Freeland, KN; Knox, JE, 2015)	1.09
" To improve on drug compliance attending physicians need to prescribe more of the relatively cheaper AED like the phenobarbitone and to optimize drug dosage before switching to another."	( A 3 year audit of adult epilepsy care in a Nigerian tertiary hospital (2011-2013). Ademiluyi, BA; Alaofin, WA; Bello, HA; Busari, K; Desalu, OO; Sanya, EO; Wahab, KW, )	0.13
" The median dosage at onset was 36."	( Lamotrigine-induced severe cutaneous adverse reaction: Update data from 1999-2014. Huang, XS; Lang, SY; Lv, B; Tian, CL; Wang, HF; Wang, XQ; Yu, SY; Zhang, JT; Zhang, X, 2015)	0.42
" When the results of CYP2C9 genotyping and CYP2C9 expression were combined, the patients' VPA-metabolizing capacity was predicted, and VPA dosing was adjusted to the patients' CYP2C9-status."	( Clinical significance of CYP2C9-status guided valproic acid therapy in children. Bűdi, T; Garami, M; Háfra, E; Kiss, Á; Monostory, K; Nagy, A; Szever, Z; Tapodi, A; Temesvári, M; Tóth, K, 2015)	0.68
"The knowledge of pediatric patients' CYP2C9-status can contribute to the optimization of VPA dosing and to the avoidance of misdosing-induced side effects."	( Clinical significance of CYP2C9-status guided valproic acid therapy in children. Bűdi, T; Garami, M; Háfra, E; Kiss, Á; Monostory, K; Nagy, A; Szever, Z; Tapodi, A; Temesvári, M; Tóth, K, 2015)	0.68
" The dose-response to DHA was obtained 15 min after intracerebroventricular (i."	( Synergistic effect of docosahexaenoic acid on anticonvulsant activity of valproic acid and lamotrigine in animal seizure models. Babapour, V; Gavzan, H; Sardari, S; Sayyah, M, 2015)	0.65
" Hepatic and renal APEH activity was negligible even at 24 h after dosing of MEPM to a dog."	( In vivo inhibition of acylpeptide hydrolase by carbapenem antibiotics causes the decrease of plasma concentration of valproic acid in dogs. Fusegawa, K; Goda, R; Ikenaga, H; Izumi, T; Kobayashi, N; Kuga, H; Nakai, D; Suzuki, E, 2016)	0.64
" There was no support for a dose-response relationship for any drug combination."	( Skating on thin ice: pragmatic prescribing for medication refractory schizophrenia. Joyce, DW; Mateos Fernandez, MJ; Sarkar, SN; Shergill, SS; Tracy, DK, 2015)	0.42
"To assess efficacy/tolerability of ezogabine (EZG)/retigabine (RTG) in combination with specified monotherapy antiepileptic drug (AED) treatments in adults with uncontrolled partial-onset seizures using a flexible dosing regimen."	( Efficacy and safety of ezogabine/retigabine as adjunctive therapy to specified single antiepileptic medications in an open-label study of adults with partial-onset seizures. Brandt, C; Daniluk, J; DeRossett, S; Edwards, S; Lerche, H; Lotay, N, 2015)	0.42
"NCT01227902 was an open-label, uncontrolled study of flexibly dosed EZG/RTG."	( Efficacy and safety of ezogabine/retigabine as adjunctive therapy to specified single antiepileptic medications in an open-label study of adults with partial-onset seizures. Brandt, C; Daniluk, J; DeRossett, S; Edwards, S; Lerche, H; Lotay, N, 2015)	0.42
"EZG/RTG was effective as adjunctive therapy to CBZ/OXC, LTG, LEV, and VPA, using a flexible dosing regimen, in adults with partial-onset seizures; safety and tolerability were consistent with that previously observed."	( Efficacy and safety of ezogabine/retigabine as adjunctive therapy to specified single antiepileptic medications in an open-label study of adults with partial-onset seizures. Brandt, C; Daniluk, J; DeRossett, S; Edwards, S; Lerche, H; Lotay, N, 2015)	0.42
" In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeutics."	( Limited Effect of Chronic Valproic Acid Treatment in a Mouse Model of Machado-Joseph Disease. Duarte-Silva, S; Esteves, S; Maciel, P; Naia, L; Neves-Carvalho, A; Rego, AC; Silva-Fernandes, A; Teixeira-Castro, A, 2015)	0.72
" Maternal levels and dosing information were used for estimating the maternal apparent oral clearance and the paired umbilical cord and maternal levels for estimation of umbilical cord/maternal level ratios."	( Serum levels of valproic acid during delivery in mothers and in umbilical cord - correlation with birth length and weight. Brozmanova, H; Grundmann, M; Kacirova, I, 2015)	0.76
"Sodium valproate is a widely used antiepileptic drug at high dosage levels, but it has been shown to produce a variety of toxic side-effects when used during perinatal period."	( [Effects of histone deacetylase inhibitor sodium valproate on the physical and behavioral development of 129SV mice]. Aleksandrova, EA; Burenkova, OV; Zarayskaya, IY, )	0.13
" The proposed methods were successfully applied to the assay of sodium valproate in tablets and oral solution dosage forms with good accuracy and precision."	( Validated spectrophotometric methods for determination of sodium valproate based on charge transfer complexation reactions. Abdel-Khalek, MM; Abo-Gharam, AH; Belal, TS; El-Kafrawy, DS; Mahrous, MS, 2016)	0.43
"Characterization of dose-response relationships for psychotropic agents may be difficult to determine based on results of individual clinical studies, particularly those with a flexible dose design."	( Lurasidone Dose Response in Bipolar Depression: A Population Dose-response Analysis. Chapel, S; Chiu, YY; Cucchiaro, J; Hsu, J; Loebel, A, 2016)	0.43
" A linear dose-response model best described the effect of lurasidone."	( Lurasidone Dose Response in Bipolar Depression: A Population Dose-response Analysis. Chapel, S; Chiu, YY; Cucchiaro, J; Hsu, J; Loebel, A, 2016)	0.43
"This population dose-response modeling analysis indicates that higher doses of lurasidone are likely to produce greater therapeutic effects in patients with bipolar depression."	( Lurasidone Dose Response in Bipolar Depression: A Population Dose-response Analysis. Chapel, S; Chiu, YY; Cucchiaro, J; Hsu, J; Loebel, A, 2016)	0.43
" We demonstrated that histone deacetylase inhibitors (HDACi), including low anticonvulsant dosage of VPA, induced the dose- and time-dependent up-regulation of TP transcript and protein expression in breast cancer cells, but not in the non-tumorigenic breast MCF-10A cell line."	( Valproic acid potentiates the anticancer activity of capecitabine in vitro and in vivo in breast cancer models via induction of thymidine phosphorylase expression. Bruzzese, F; Budillon, A; D'Angelo, G; Di Gennaro, E; Franco, R; Leone, A; Roca, MS; Russo, D; Scogliamiglio, G; Terranova-Barberio, M; Vitagliano, C; Zotti, AI, 2016)	1.88
" This population PK model can be applied for optimizing topiramate dosage regimens in actual clinical practice."	( Factors influencing topiramate clearance in adult patients with epilepsy: A population pharmacokinetic analysis. Bae, EK; Jang, IJ; Kim, TJ; Lee, J; Lee, KJ; Lee, SK; Moon, J; Shin, D; Shin, JW; Shin, YW, 2016)	0.43
" Patients were randomly assigned to three groups of four subjects, each with an oral dosage of 400 mg, 600 mg, or 800 mg (twice daily (bid) for one day)."	( Safety and efficacy of valproic acid treatment in SCA3/MJD patients. Chuang, DM; Jiang, H; Lei, LF; Song, WH; Tang, BS; Wang, JL; Yang, GP, 2016)	0.74
" The correlation with dose may be a spurious finding related to the fact that physicians, in adjusting dosage according to clinical response, are more likely to use larger doses in patients with high clearance values."	( An investigation of the influence of patient-related factors and comedications on lamotrigine clearance in patients with epilepsy. Alexandre, V; Baldoni, AO; de Santi Ferreira, FI; Freitas-Lima, P; Martinez, EZ; Pereira, LR; Perucca, E; Queiroz, RH; Sakamoto, AC, 2016)	0.43
" No correlation was found between duration or dosage of VPA and BMDs."	( Bone health and vitamin D status in young epilepsy patients on valproate monotherapy. Albaghdadi, O; Alhalabi, MS; Alourfi, Z; Youssef, LA, 2016)	0.43
" In order to obtain similar drug exposure, our findings suggest that older female patients would generally require 30-50 % lower dosing of VPA compared to younger males."	( Impact of age, gender and CYP2C9/2C19 genotypes on dose-adjusted steady-state serum concentrations of valproic acid-a large-scale study based on naturalistic therapeutic drug monitoring data. Haslemo, T; Molden, E; Refsum, H; Smith, RL, 2016)	0.65
" The objective of this study is to characterize the pharmacokinetics of continuous infusion of VPA in acutely ill patients and to determine dosing regimens that most frequently obtain goal steady-state serum concentrations."	( Steady-state pharmacokinetic simulation of intermittent vs. continuous infusion valproic acid therapy in non-critically ill and critically ill patients. Cook, AM; Van Matre, ET, 2016)	0.66
" Intermittent and continuous infusion dosing strategies were modeled utilizing Monte Carlo simulations for both cohorts."	( Steady-state pharmacokinetic simulation of intermittent vs. continuous infusion valproic acid therapy in non-critically ill and critically ill patients. Cook, AM; Van Matre, ET, 2016)	0.66
" Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects."	( Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study. Geddes, JR; Hayes, JF; King, M; Marston, L; Osborn, DP; Walters, K, 2016)	0.43
"The aim of this review was to evaluate current literature for dosing recommendations for the use of antiepileptic medications in patients receiving renal replacement therapy (RRT)."	( Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. Bastin, ML; Cook, AM; Oyler, DR; Smetana, KS, 2016)	0.43
" Micromedex® DRUGDEX as well as package inserts were used to obtain known pharmacokinetic properties and dosage adjustment recommendations in RRT if known."	( Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. Bastin, ML; Cook, AM; Oyler, DR; Smetana, KS, 2016)	0.43
"Data regarding antiepileptic drug use in RRT are limited and mostly consist of case reports limiting our proposed dosing recommendations."	( Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. Bastin, ML; Cook, AM; Oyler, DR; Smetana, KS, 2016)	0.43
"Additional studies are necessary before specific dosing recommendations can be made for most antiepileptic drugs in critically ill patients receiving RRT, specifically with newer agents."	( Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. Bastin, ML; Cook, AM; Oyler, DR; Smetana, KS, 2016)	0.43
" To determine the role of gene overexpression on chromosome instability (CIN), we performed genome-wide screens in the budding yeast for yeast genes that cause CIN when overexpressed, a phenotype we refer to as dosage CIN (dCIN), and identified 245 dCIN genes."	( Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer. Andrews, B; Ang, JS; Boerkoel, CF; Duffy, S; Fam, HK; Hieter, P; Kim, JH; Larionov, V; Shah, SP; Singh, T; Styles, EB; Wang, YK, 2016)	0.43
" Thus, this study shows that VPA can be dosed to selectively manipulate the fibrinolytic system in the vascular compartment and reduce thrombus formation in vivo."	( Valproic acid selectively increases vascular endothelial tissue-type plasminogen activator production and reduces thrombus formation in the mouse. Alwis, I; Bergh, N; Daglas, M; Fogelstrand, P; Glise, L; Jackson, SP; Jern, S; Larsson, P; Magnusson, M; Medcalf, RL; Niego, B; Sashindranath, M; Wu, MC, 2016)	1.88
" Thus, genotype-directed dosing could improve pharmacotherapy by reducing the risk of toxicities or preventing suboptimal treatment."	( Pharmacogenomics and histone deacetylase inhibitors. Figg, WD; Goey, AK; Peer, CJ; Sissung, TM, 2016)	0.43
" There is no need to limit brivaracetam dosing when used concomitantly with carbamazepine."	( Pharmacokinetic interaction of brivaracetam on carbamazepine in adult patients with epilepsy, with and without valproate co-administration. Brodie, MJ; Sargentini-Maier, ML; Stockis, A, 2016)	0.43
" The initial dosage of TPM was 1-3 mg·kg·d."	( Topiramate Blood Levels During Polytherapy for Epilepsy in Children. Ishii, M; Iwasaki, T; Toki, T, )	0.13
"Measuring blood levels of TPM based on the classification of concomitant drugs and adjusting the dosage to reach the optimal range were recommended."	( Topiramate Blood Levels During Polytherapy for Epilepsy in Children. Ishii, M; Iwasaki, T; Toki, T, )	0.13
" However, dissolution models addressing the particular features of pediatric gastrointestinal physiology and typical pediatric dosing scenarios have not yet been described."	( Simulating Different Dosing Scenarios for a Child-Appropriate Valproate ER Formulation in a New Pediatric Two-Stage Dissolution Model. Karkossa, F; Klein, S; Krueger, A; Urbaniak, J, 2017)	0.46
" The UHPLC-MS/MS method demonstrated a good analytical performance essential for therapeutic drug monitoring, which would potentially lead to clinically relevant improvements in VPA dosage and patient management."	( Simultaneous Determination of Valproic Acid and Its Major Metabolites by UHPLC-MS/MS in Chinese Patients: Application to Therapeutic Drug Monitoring. Li, G; Qiu, F; Sun, Y; Zhang, T; Zhao, L; Zhao, M, 2017)	0.74
" The maximal in vivo VPA dosage that showed no significant cytotoxicity compared with control was 10 mg/kg/day."	( Synergistic effect of cytokine-induced killer cell with valproate inhibits growth of hepatocellular carcinoma cell in a mouse model. Chang, Y; Cho, E; Cho, H; Cho, YY; Kang, SH; Kim, YJ; Lee, DH; Lee, JH; Nam, JY; Yoon, JH; Yu, SJ, 2017)	0.46
" The dosage of PB was ranked first followed by that of CBZ and finally by the VPA."	( [Therapeutic drug monitoring of three antiepileptic drugs - Back on twenty years of experience]. Badrane, N; Bencheikh, RS; Moussa, LA; Ouammi, L; Serragui, S; Tanani, DS; Zalagh, F, 2016)	0.43
" Additional research to define best practice for dosing and monitoring valproate and the relationship between free valproate concentrations and clinical or adverse effects in ICU patients is needed."	( Valproate Protein Binding Is Highly Variable in ICU Patients and Not Predicted by Total Serum Concentrations: A Case Series and Literature Review. Fraser, GL; Gagnon, DJ; Hatton, C; May, T; Riker, RR; Seder, DB; Stokem, K, 2017)	0.46
" We sought to determine whether there were regions in the dosage range of commonly used AEDs that were associated with superior efficacy in patients with refractory epilepsy."	( Association between antiepileptic drug dose and long-term response in patients with refractory epilepsy. Castagna, CE; Miller, AB; Poolos, NP; Story, TJ; Williams, S, 2017)	0.46
"The aims of the study were to develop a population pharmacokinetic model of orally administered brivaracetam in paediatric patients and to provide dosing suggestions."	( Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years. Schoemaker, R; Stockis, A; Wade, JR, 2017)	0.46
" Simulations were performed to investigate dosing regimens."	( Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years. Schoemaker, R; Stockis, A; Wade, JR, 2017)	0.46
" Data suggest no need to change brivaracetam dosing when used concomitantly with carbamazepine, phenobarbital or valproate."	( Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years. Schoemaker, R; Stockis, A; Wade, JR, 2017)	0.46
" Criterion 2=the last drug introduced into the antiepileptic therapy within 72h before the cessation of SE and without changes in dosage or number of the co-medication."	( The efficacy of different kinds of intravenously applied antiepileptic drugs in the treatment of status epilepticus. How can it be determined? Redecker, J; Rösche, J; Wittstock, M, 2017)	0.46
"In Chinese patients, after craniotomy, female patients with 1 or more of CYP2C9 (1075 AC) and UGT1A6 (552 AA) genotypes required a lower VPA dosage compared with male patient."	( Analysis of the Variables Influencing Valproic Acid Concentration in the Serum and Cerebrospinal Fluid of Chinese Patients After Craniotomy. Chen, W; Gao, W; Li, Z; Liu, G, 2017)	0.73
" Here, we showed that valproic acid (VPA), a histone deacetylase inhibitor, enforced the priming effect of S1P at a low dosage for human umbilical cord-derived MSCs (UC-MSCs)."	( Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells. Choi, KC; Heo, J; Ju, H; Kim, IG; Kim, Y; Lee, HY; Lee, S; Lim, J; Oh, YM; Shin, DM; Son, J, 2017)	2.21
" Hydralazine was dosed according to the acetylation genotype of patients (slow acetylators 83 mg daily; fast acetylators 182 mg daily), and valproate was dosed at 30 mg/kg/day."	( Encouraging results with the compassionate use of hydralazine/valproate (TRANSKRIP™) as epigenetic treatment for myelodysplastic syndrome (MDS). Burgos, S; Candelaria, M; Dueñas-Gonzalez, A; Espinoza, R; Ponce, M, 2017)	0.46
" As health care professionals, it is prudent to be familiar with their dosing regimens, common adverse effects, and the monitoring required to maximize patient benefits and minimize harms."	( Oral Agents for the Management of Agitation and Agitated Delirium in Critically Ill Patients. Hammond, DA; Smith, MN; Wiley, TL; Yeo, QM, )	0.13
" There was a dose-response effect, with greater associations for higher doses."	( Sodium valproate and clozapine induced neutropenia: A case control study using register data. Ajnakina, O; Flanagan, RJ; Gaughran, F; Krivoy, A; Lally, J; MacCabe, JH; Malik, S; Pritchard, M; Shetty, H, 2018)	0.48
"Tablets and capsules are the most accepted and widely used solid dosage forms in the medical therapy."	( Application of Spray Drying Technique for Flowability enhancement of Divalproex Sodium. Asdagh, A; Ghanbarzadeh, S; Hamishehkar, H; Valizadeh, H; Yaqoubi, S, 2018)	0.48
"Drug half-life has important implications for dosing regimen and peak-to-trough ratio at the steady state."	( Relevance of Half-Life in Drug Design. Beaumont, K; Di, L; Maurer, TS; Smith, DA, 2018)	0.48
" The early knowledge of pediatric patients' CYP2C9-status facilitates the optimization of valproate dosing which contributes to the avoidance of misdosing induced adverse reactions, such as abnormal blood levels of ammonia and alkaline phosphatase, and improves the safety of children's anticonvulsant therapy."	( Relevance of CYP2C9 Function in Valproate Therapy. Bűdi, T; Csukly, G; Déri, M; Kiss, Á; Monostory, K; Nagy, A; Tóth, K, 2019)	0.51
" 25-OHD levels were categorized as low (<20ng/ml), borderline (20-29ng/ml), or normal (>30ng/ml) RESULTS: The average dosage of VPA and LEV was 20."	( Vitamin D deficiency in children with epilepsy taking valproate and levetiracetam as monotherapy. Aguilera-Albesa, S; Durá-Travé, T; Gallinas-Victoriano, F; Malumbres-Chacón, M; Moreno-Gónzalez, P; Yoldi-Petri, ME, 2018)	0.48
"There were 13 cases of VPE; 12 were associated with therapeutic dosing and 1 with an overdose."	( Levocarnitine for the Treatment of Valproic Acid-Induced Hyperammonemic Encephalopathy in Children: The Experience of a Large, Tertiary Care Pediatric Hospital and a Poison Center. Bonifacio Rino, P; de Pinho, S; Glatstein, M; Hoyte, C; Pivko-Levi, D; Scolnik, D, )	0.41
"Population pharmacokinetics is an essential tool that helps guide individualized dosing regimens."	( A systematic review of population pharmacokinetics of valproic acid. Methaneethorn, J, 2018)	0.73
" The LTG PPK model developed in this study could be useful for individualizing LTG dosage regimens in pediatric patients receiving combination therapy, especially therapy that includes VPA."	( Population pharmacokinetics of lamotrigine co-administered with valproic acid in Chinese epileptic children using nonlinear mixed effects modeling. Chen, Y; Liu, L; Liu, M; Liu, S; Lu, T; Wang, H; Xu, S; Zhao, L; Zhao, M, 2018)	0.72
" This dosing strategy results in less serum concentration fluctuations, more consistent therapeutic effects, and less adverse effects."	( Continuous Intravenous Valproate as Abortive Therapy for Pediatric Status Migrainosus. Baumann, RJ; Cook, AM; Stewart, AM; Toupin, DN; Zafar, MS, 2018)	0.48
" Insulin therapy was practiced, with progressive dosage reduction, until complete cessation of treatment after 13 months."	( Second-generation antipsychotic and diabetes mellitus in children and adolescents. Nurchi, AM; Pinna, AP; Podda, F; Ripoli, C; Tronci, MG; Zanni, R, 2017)	0.46
"Despite stable LTG dosage serum concentrations on study day 20, 22, 24, 26, and 28, all were significantly lower compared to baseline (p < 0."	( Time course of reversal of valproate-mediated inhibition of lamotrigine. Gidal, BE; Leary, E; Sheth, RD, 2018)	0.48
" These data provide clinically useful information in developing a dosing algorithm for converting patients to LTG monotherapy."	( Time course of reversal of valproate-mediated inhibition of lamotrigine. Gidal, BE; Leary, E; Sheth, RD, 2018)	0.48
" While women younger than 50 years of age were less likely to be prescribed valproate than men in the same age group, and at a lower dosage, it is unclear to what extent this reflects clinicians' concerns about teratogenicity or is driven by perceptions of the indication for valproate, and the dosage required, for the treatment of different phases of the disorder in men and women."	( A UK clinical audit addressing the quality of prescribing of sodium valproate for bipolar disorder in women of childbearing age. Barnes, TRE; Bhatti, S; Cookson, J; Fagan, E; Ferrier, IN; Paton, C, 2018)	0.48
"Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used."	( Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Battino, D; Bonizzoni, E; Craig, J; Lindhout, D; Perucca, E; Sabers, A; Thomas, SV; Tomson, T; Vajda, F, 2018)	0.48
" We observed a 56% decline in half-life with short-term meropenem dosing and an improvement in mental status shortly after administration."	( Intentional use of carbapenem antibiotics for valproic acid toxicity: A case report. Biggs, AD; Dudley, SW; Erstad, BL; French, RNE; Huckleberry, YC; Khobrani, MA; Kopp, BJ; Shirazi, FM, 2018)	0.74
" It was verified that exposure to VPA, close to typical dosage values (0."	( A scale out approach towards neural induction of human induced pluripotent stem cells for neurodevelopmental toxicity studies. Cabral, JMS; Diogo, MM; Fernandes, TG; Miranda, CC; Pinto, SN; Prieto, M, 2018)	0.48
" If only valproate therapy owns the ability to obtain seizure freedom, then stopping its administration is not suggested, but a low dosage has to be aimed (500-600 mg/day, but not more than 1000 mg/day): according to some studies, most idiopathic generalized epilepsies can be controlled by low valproate dosage."	( [Valproate in the treatment of epilepsy and status epilepticus]. Bóné, B; Janszky, J; Tényi, D, 2017)	0.46
" However, the oral dosage of valproate during the remission/recovery period (944."	( Rate of Serum Valproate Concentration Monitoring in Patients with Bipolar Disorder Type I at Srinagarind Hospital Outpatient Clinic. Paholpak, P; Paholpak, S; Patanasethanant, D; Patjanasoontorn, N; Rangseekajee, P, 2016)	0.43
" The dosage can be adjusted using only clinical response and adverse effects."	( Rate of Serum Valproate Concentration Monitoring in Patients with Bipolar Disorder Type I at Srinagarind Hospital Outpatient Clinic. Paholpak, P; Paholpak, S; Patanasethanant, D; Patjanasoontorn, N; Rangseekajee, P, 2016)	0.43
" The results show that utilising a 2839 gene panel, it is possible to discriminate basal tissue-specific signatures, generate dose-response relationships and to discriminate compound-specific and cell type-specific responses."	( Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq. Ates, G; Carta, G; Jennings, P; Limonciel, A; Seligmann, B; Shepard, PJ; van de Water, B; VanSteenhouse, HC; Vinken, M; Watzele, M; Wilmes, A; Yeakley, JM, 2018)	0.48
" All patients were under valproate (VPA) treatment, and the mean VPA dosage was 783."	( Frontal lobe cognitive functions and electroencephalographic features in juvenile myoclonic epilepsy. Ak, PD; Ataklı, D; Keskinkılıç, C; Pulat, TA; Sezikli, S; Tekin, B, 2018)	0.48
" Our dose-response study indicated that the optimal concentration of VPA was 1 mM at 72 h."	( Immunocytochemical analysis of valproic acid induced histone H3 and H4 acetylation during differentiation of rat adipose derived stem cells into neuron-like cells. Abdanipour, A; Hassoun, HK; Rezaei, F; Taheri, T; Tiraihi, T, 2018)	0.77
"Significant decreases in pregnancy weight gain and the number of live fetuses were observed when VPA was administered at the high dose, whereas the percentage of exencephalic fetuses was significantly increased in VPA treated compared with an equivalent VCD dosage group."	( Teratogenicity of valproic acid and its constitutional isomer, amide derivative valnoctamide in mice. Bialer, M; Cabrera, RM; Finnell, RH; Lin, YL; Wlodarczyk, BJ, 2019)	0.85
" Through simulations with the best model, we evaluated dosing regimen."	( Simulations of Valproate Doses Based on an External Evaluation of Pediatric Population Pharmacokinetic Models. Aboura, R; Benaboud, S; Billette de Villemeur, T; Bouazza, N; Chenevier-Gobeaux, C; Desguerre, I; Freihuber, C; Gana, I; Hirt, D; Nabbout, R; Tauzin, M; Tréluyer, JM; Zheng, Y, 2019)	0.51
" Patients' basic information, dosage regimens, and plasma concentrations were recorded."	( Lack of association between valproic acid response and polymorphisms of its metabolism, transport, and receptor genes in children with focal seizures. Fang, F; Feng, W; Gao, B; Han, J; Li, J; Mei, S; Wu, Y; Yu, Y; Zhao, Z; Zhu, L, 2019)	0.81
" In the clinical setting, these findings can help to estimate LTG concentrations and adjust dosage and evaluate adverse drug reactions."	( The influence of concomitant antiepileptic drugs on lamotrigine serum concentrations in Northwest Chinese Han population with epilepsy. Han, X; Huang, J; Lv, J; Ma, L; Nie, X; Peng, L; Wang, J; Xia, L; Zan, X, 2019)	0.51
" The total CRST score was significantly associated with epilepsy duration and maximum VPA dosage (B = 0."	( The clinical characteristics and related factors of tremor in patients with epilepsy. Chen, J; Jiang, X; Lu, L; Xiao, Y; Xiong, W; Zhang, Y; Zhou, D, 2019)	0.51
" Epilepsy duration and maximum VPA dosage were important factors of tremor severity, suggesting mechanisms underlying tremor in PWE may be an elaborate interplay of AEDs and disease itself."	( The clinical characteristics and related factors of tremor in patients with epilepsy. Chen, J; Jiang, X; Lu, L; Xiao, Y; Xiong, W; Zhang, Y; Zhou, D, 2019)	0.51
" Interestingly, regarding VPA dosage, we found that women taking equal or more than 700 mg/day of VPA have lower scores on empowerment in all dimensions compared with women with a VPA dosage lower than 700 mg/day."	( Level of empowerment and decision-making style of women with epilepsy in childbirth age. Canevini, MP; Cutica, I; Pravettoni, G; Riva, S; Turner, K; Zambrelli, E, 2019)	0.51
" Collectively, healthcare providers should take these factors in consideration for optimal valproic acid dosage regimen."	( Estimation of apparent clearance of valproic acid in adult Saudi patients. Alandas, N; Alqahtani, S; Alsultan, A, 2019)	1.01
" In this experimental animal study of early chick embryo model, we would like to determine if there is any dose-response relationship between VA and NTDs and if there is any protective effect of FA on this relationship in early chick embryo period."	( Valproic acid effect on neural tube defects is not prevented by concomitant folic acid supplementation: Early chick embryo model pilot study. Cakin, H; Kazan, S; Ozak, A; Turgut, U, 2019)	1.96
" Multiple daily doses of olanzapine do not affect the pharmacokinetics of lithium or valproate; therefore, concomitant olanzapine administration does not require dosage adjustment of lithium or valproate."	( Combination of Olanzapine and Samidorphan Has No Clinically Significant Effect on the Pharmacokinetics of Lithium or Valproate. Graham, C; Sun, L; von Moltke, L; Yagoda, S; Yao, B, 2020)	0.56
" Pharmacokinetic parameters of lithium and valproate, including maximum plasma concentration and area under the plasma concentration-time curve over a 12-h dosing interval, were calculated."	( Combination of Olanzapine and Samidorphan Has No Clinically Significant Effect on the Pharmacokinetics of Lithium or Valproate. Graham, C; Sun, L; von Moltke, L; Yagoda, S; Yao, B, 2020)	0.56
" absence of OLZ/SAM, were within the equivalence interval of 80-125% for both maximum plasma concentration and area under the plasma concentration-time curve over a 12-h dosing interval of lithium and of valproate."	( Combination of Olanzapine and Samidorphan Has No Clinically Significant Effect on the Pharmacokinetics of Lithium or Valproate. Graham, C; Sun, L; von Moltke, L; Yagoda, S; Yao, B, 2020)	0.56
" CIMT and EATT values were not associated with the dosage and duration of each antiepileptic drug."	( Effects of valproic acid and levetiracetam monotherapy on carotid intima-media and epicardial adipose tissue thickness in non-obese children with epilepsy. Karatoprak, E; Tosun, O, 2020)	0.95
" In 2009, a review was published providing guidance for the dosing and therapeutic drug monitoring of antiepileptic drugs during pregnancy."	( Therapeutic Drug Monitoring of Antiepileptic Drugs in Women with Epilepsy Before, During, and After Pregnancy. Arfman, IJ; Lambrechts, DA; Ter Horst, PGJ; Touw, DJ; Wammes-van der Heijden, EA; Wegner, I, 2020)	0.56
"These results indicate that this repetitive dosing valproate sodium protocol is a safe and well-tolerated intervention for the treatment of chronic migraine resistant to oral medications."	( Retrospective Chart Review of Intravenous Valproate Sodium as a Preventive Treatment for Patients With Chronic Migraine. Dapkus, L; Ehrlich, A; Levin, M; Riggins, N; Sawhney, H, 2020)	0.56
" We compared ab initio model predictions to data obtained on culture medium and embryo concentrations of valproic acid (VPA) and nine analogs during continuous dosing under the OECD test guideline 236."	( Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs. Bois, FY; Braunbeck, T; Brotzmann, K; Fisher, C; Gardner, I; Maclennan, R; Silvester, S; Siméon, S; Walker, P, 2020)	0.98
"5, and VPA (800 mg/kg) was administered orally in a single dosage on gestational day 12."	( Quercetin prevents alterations of behavioral parameters, delta-aminolevulinic dehydratase activity, and oxidative damage in brain of rats in a prenatal model of autism. Baldissarelli, J; de Mattos, BDS; de Souza, AA; Gamaro, GD; Pedra, NS; Soares, MSP; Spanevello, RM; Spohr, L; Stefanello, FM; Teixeira, FC, 2020)	0.56
"Five groups of each of 12 female rats were orally dosed daily for 8 weeks with either carbamazepine (CBZ) (60 mg/kg), eslicarbazepine (ESL) (80 mg/kg), valproic acid (VPA) (300 mg/kg), levetiracetam (LEV) (50 mg/kg) or saline (control (CTL))."	( Effects of carbamazepine, eslicarbazepine, valproic acid and levetiracetam on bone microarchitecture in rats. Andersen, NB; Diemar, SS; Ding, M; Eiken, P; Ellegaard, M; Jørgensen, NR; Sejling, AS, 2020)	1.02
" During radiation and VPA, grade 3 or higher toxicities requiring discontinuation or modification of VPA dosing included grade 3 thrombocytopenia (1), grade 3 weight gain (1), and grade 3 pancreatitis (1)."	( A phase 2 study of valproic acid and radiation, followed by maintenance valproic acid and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma or high-grade glioma. Adesina, AM; Baxter, PA; Blaney, SM; Bowers, DC; Jo, E; McNall-Knapp, RY; Mo, Q; Murray, JC; Paulino, AC; Shah, S; Su, JM, 2020)	0.89
"Prepregnancy reduction in VPA dosage reduced the hazard of fetal malformations, whereas ceasing intake of the drug decreased the hazard to one similar to that which applies in the general population, but at a cost of decreased control of epileptic seizures during the pregnancies studied."	( Pregnancy after valproate withdrawal-Fetal malformations and seizure control. Eadie, MJ; Graham, JE; Hitchcock, AA; Lander, CM; O'Brien, TJ; Vajda, FJE, 2020)	0.56
" The final mean dosage of rufinamide was 31."	( Rufinamide as add-on therapy in children with epileptic encephalopathies other than Lennox-Gastaut syndrome: A study of 34 patients. Caraballo, RH; Espeche, A; Fasulo, L; Galichio, S; Pociecha, J; Reyes, G; Semprino, M, 2020)	0.56
" Weight-based dosing was capped at 75 kg."	( The association of patient weight and dose of fosphenytoin, levetiracetam, and valproic acid with treatment success in status epilepticus. Bleck, TP; Chamberlain, JM; Cloyd, JC; Cock, HR; Coles, LD; Conwit, RA; Elm, JJ; Fountain, NB; Kapur, J; Lowenstein, DH; Sathe, AG; Shinnar, S; Silbergleit, R, 2020)	0.79
" Both, the type I isobolographic analysis and the test of parallelism of dose-response effects of the ASDs were used so as to properly classify interaction among three ASDs, administered in a fixed ratio combination of 1:1:1."	( Sub-additive (antagonistic) interaction of lacosamide with lamotrigine and valproate in the maximal electroshock-induced seizure model in mice: an isobolographic analysis. Bojar, H; Florek-Łuszczki, M; Karwan, S; Kondrat-Wróbel, M; Plewa, Z; Zagaja, M; Łuszczki, JJ, 2020)	0.56
"9)), with a dose-response relationship."	( Risk of early neurodevelopmental outcomes associated with prenatal exposure to the antiepileptic drugs most commonly used during pregnancy: a French nationwide population-based cohort study. Blotière, PO; Coste, J; Dray-Spira, R; Mahmoud, Z; Mikaeloff, Y; Miranda, S; Peyre, H; Ramus, F; Weill, A, 2020)	0.56
" Finally, stochastic simulations were carried out to propose dosage regimens."	( Dosing Recommendations Based on Population Pharmacokinetics of Lamotrigine in Mexican Adult Patients With Epilepsy. Chávez-Castillo, CE; Medellín-Garibay, SE; Milán-Segovia, RDC; Rodríguez-Leyva, I; Romano-Moreno, S, 2020)	0.56
" This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of valproic acid (VPA) in patients with epilepsy and established remedial dosing recommendations for nonadherent patients."	( Remedial dosing recommendations for delayed or missed doses of valproic acid in patients with epilepsy based on Monte Carlo simulations. Ding, JJ; Jiao, Z; Wang, CY; Yu, EQ; Zhu, GX, 2020)	1.02
" Remedial dosing strategies A and B were almost equivalent, whereas Strategy C was recommended when the delayed dose was close to the next scheduled dose."	( Remedial dosing recommendations for delayed or missed doses of valproic acid in patients with epilepsy based on Monte Carlo simulations. Ding, JJ; Jiao, Z; Wang, CY; Yu, EQ; Zhu, GX, 2020)	0.8
"9% were treated with valproate with a mean daily dosage of 968 mg."	( Evolution and characteristics of the use of valproate in women of childbearing age with bipolar disorder: Results from the FACE-BD cohort. Aouizerate, B; Aubin, V; Bellivier, F; Belzeaux, R; Bennabi, D; Bougerol, T; Courtet, P; Dubertret, C; Encely, L; Etain, B; Gard, S; Godin, O; Haffen, E; Henry, C; Leboyer, M; Llorca, PM; Loftus, J; Mazer, N; Olié, E; Passerieux, C; Pelletier, A; Poinso, F; Polosan, M; Roux, P; Samalin, L; Schwan, R; Schwitzer, T, 2020)	0.56
"Bootstrap and VPC indicated that a reliable model had been developed that was based on the simulation results, and a simple-to-use dosage regimen table was created to guide clinicians for VPA drug dosing."	( Impact of gender, albumin, and CYP2C19 polymorphisms on valproic acid in Chinese patients: a population pharmacokinetic model. Guo, J; Guo, Z; Han, H; Huo, Y; Li, F; Li, Y; Zhou, Y, 2020)	0.8
"The genetic polymorphisms of CYP2C19 significantly affect the VPA plasma concentration, and the dosage of VPA for intermediate and poor metabolisers could be lower than for extensive metabolisers."	( Impact of CYP2C19 and CYP2C9 gene polymorphisms on sodium valproate plasma concentration in patients with epilepsy. Li, X; Liu, L; Mao, P; Song, C; Song, W; Zhang, Y, 2022)	0.72
"A total of 3 194 Chinese epileptic outpatients from Xiangya Hospital, were analyzed in a crude analysis after stratifying through dosage regimens."	( Valproic acid concentration and biochemical indexes in epilepsy outpatients during monotherapy or combination therapy. Luo, J; Ma, H; Pan, J; Wang, C; Wang, P; Yang, X, 2020)	2
"In cell biology, pharmacology and toxicology dose-response and concentration-response curves are frequently fitted to data with statistical methods."	( Handling deviating control values in concentration-response curves. Albrecht, W; Blum, J; Brecklinghaus, T; Hengstler, JG; Kappenberg, F; Leist, M; Rahnenführer, J; van der Wurp, C, 2020)	0.56
"If MfVPA is not available, the albumin-adjusted formula should be applied before VPA dosage adjustment when TVPA is < 56."	( Factors to influence the accuracy of albumin adjusted free valproic acid concentration. Huang, SY; Kuo, CH; Tseng, YJ; Wang, CY; Wang, KC; Wu, CC, 2021)	0.86
"VPA PopPK models developed using patients with epilepsy can also be used for individualized dosing of patients with mania, but before implementation, the accuracy of these models' predictions should be assessed in the target population."	( Predictive ability of published population pharmacokinetic models of valproic acid in Thai manic patients. Leelakanok, N; Methaneethorn, J, 2021)	0.86
" A dose-response relationship was demonstrated and the risk of NDs was more particularly increased for an exposure to VPA during the second or third trimesters of pregnancy."	( Risk of early neurodevelopmental disorders associated with in utero exposure to valproate and other antiepileptic drugs: a nationwide cohort study in France. Blotiere, PO; Coste, J; Dray-Spira, R; Mikaeloff, Y; Miranda, S; Peyre, H; Ramus, F; Weill, A; Zureik, M, 2020)	0.56
"Multiple variable logistic regression failed to demonstrate any statistically significant effect of folic acid dosage in reducing overall fetal malformation rates in women taking folic acid either before and during pregnancy (P = 0."	( Folic acid dose, valproate, and fetal malformations. Eadie, MJ; Graham, JE; Hitchcock, AA; Lander, CM; O'Brien, TJ; Perucca, P; Vajda, FJE, 2021)	0.62
" The dosing regimens for children aged 0 to 16 years were proposed based on the final established model."	( Population pharmacokinetics of unbound valproic acid in pediatric epilepsy patients in China: a protein binding model. Gu, X; Hu, Y; Jiao, Z; Li, Z; Ma, M; Peng, Q; Sheng, C; Yu, S; Zhou, B; Zhu, M, 2021)	0.89
" The VPA dosing regimen in pediatric patients with epilepsy needs to be optimized by the body weight, age, and co-medications."	( Population pharmacokinetics of unbound valproic acid in pediatric epilepsy patients in China: a protein binding model. Gu, X; Hu, Y; Jiao, Z; Li, Z; Ma, M; Peng, Q; Sheng, C; Yu, S; Zhou, B; Zhu, M, 2021)	0.89
"The mechanical properties of powders determine the ease of manufacture and ultimately the quality of the oral solid dosage forms."	( Modulation of the powder properties of lamotrigine by crystal forms. Kavanagh, ON; Sun, CC; Walker, GM; Wang, C, 2021)	0.62
"For the determination of acute toxicity of chemicals in zebrafish (Danio rerio) embryos, the OECD test guideline 236, relative to the Fish Embryo Toxicity Test (FET), stipulates a dose-response analysis of four lethal core endpoints and a quantitative characterization of abnormalities including their time-dependency."	( Multistate models of developmental toxicity: Application to valproic acid-induced malformations in the zebrafish embryo. Beaudouin, R; Bois, FY; Braunbeck, T; Brotzmann, K; Siméon, S, 2021)	0.86
" We aimed to evaluate the influence of sex and drug dosage on the association between prenatal VPA exposure and postnatal behavioral outcomes."	( Prenatal valproate exposure and adverse neurodevelopmental outcomes: Does sex matter? Anderson, A; Graham, J; Hitchcock, A; Honybun, E; Malpas, CB; O'Brien, TJ; Perucca, P; Rayner, G; Thwaites, R; Vajda, FJE, 2021)	0.62
" There was no evidence of any dose-response relationship between VPA exposure and ASD symptoms."	( Prenatal valproate exposure and adverse neurodevelopmental outcomes: Does sex matter? Anderson, A; Graham, J; Hitchcock, A; Honybun, E; Malpas, CB; O'Brien, TJ; Perucca, P; Rayner, G; Thwaites, R; Vajda, FJE, 2021)	0.62
" However, the blood concentration of VPA rose unexpectedly to 230 µg/mL (two- to three-fold higher than the expected value), and continued to remain relatively high even after the dosage was reduced (7 mg/kg/day, blood concentration of 88 µg/mL)."	( Unexpected elevation in valproic acid concentration and agranulocytosis in a patient with short-chain acyl-CoA dehydrogenase deficiency. Eto, K; Hara, K; Ito, S; Nagata, S; Nishikawa, A; Oguni, H; Otani, Y; Suzuki, Y, 2021)	0.93
"Valproic acid (VPA) dosing needs to be individualized for epilepsy patients through therapeutic drug monitoring (TDM)."	( Therapeutic drug monitoring of valproic acid using a dried plasma spot sampling device. Cao, H; Huang, J; Jiang, Y; Li, Y; Lin, H; Ren, W; Zhang, J, 2021)	2.35
"Logistic regression analysis showed that maternal age over 31 years, family histories of fetal malformation, and conception after assisted fertility treatment, and also dosage of valproate, carbamazepine, and topiramate, made statistically significant (P<0."	( The contribution of non-drug factors to fetal malformation in anti-seizure-medication-treated pregnancy. Eadie, MJ; Graham, JE; Hitchcock, AA; Lander, CM; O'Brien, TJ; Vajda, FJE, 2021)	0.62
" This was achieved safely through a reduced dosing schedule of three times a week post dialysis, slow dose titration and blood level monitoring prior to each dialysis session."	( Lithium use in a patient on haemodialysis with bipolar affective disorder and lithium-induced nephropathy. Salisbury, E; Topp, S, 2021)	0.62
" Furthermore, a controlled dosage of inositols, up to 6 grams/daily, may reduce the side effects caused by lithium therapy, without hindering its central therapeutic role on patients' mood."	( Combined treatment of myo-inositol and d-chiro-inositol (80:1) as a therapeutic approach to restore inositol eumetabolism in patients with bipolar disorder taking lithium and valproic acid. D'Ambrosio, F; Di Lorenzo, C; Janiri, L, 2021)	0.81
" The clinical dosage of inositols used as dietary supplementation is 4 grams/daily, and it may allow the recovery of the side effects and improve patients' QoL, without reducing the central therapeutic effect of the pharmacological therapy."	( Combined treatment of myo-inositol and d-chiro-inositol (80:1) as a therapeutic approach to restore inositol eumetabolism in patients with bipolar disorder taking lithium and valproic acid. D'Ambrosio, F; Di Lorenzo, C; Janiri, L, 2021)	0.81
" In order to name some, the administration of once-daily dosing of phenytoin or the coadministration of carnitine with valproic acid would be preferable to avoid iatrogenic refractoriness."	( The role of efflux transporters and metabolizing enzymes in brain and peripheral organs to explain drug-resistant epilepsy. Fagiolino, P; Vázquez, M, 2022)	0.93
"002), and daily dosage (> 1,000 mg/d; OR = 19."	( Investigation of the risk of valproic acid-induced tremor: clinical, neuroimaging, and genetic factors. Huang, S; Jian, S; Kang, H; Kirsch, HE; Lan, L; Li, C; Wang, M; Zhao, X; Zhou, Q; Zhu, S, 2022)	1.01
"In this study, we examined whether the pharmacokinetic profiles of sodium valproate (SVA), levetiracetam (LEV), and carbamazepine (CBZ) are affected by altering the dosing time of RACOL®-NF Semi Solid for Enteral Use (RASS), a prescribed semi-solid formula."	( Effects of concurrent and staggered dosing of semi-solid enteral nutrients on pharmacokinetic behavior of antiepileptic drugs after oral administration in rats. Fukuno, S; Hatsuda, Y; Iwanami, Y; Konishi, H; Myotoku, M; Nagai, K; Omotani, S; Ryuno, Y, 2021)	0.62
"There was no difference in pharmacokinetic characteristics of SVA and LEV when the dosing time of RASS was altered."	( Effects of concurrent and staggered dosing of semi-solid enteral nutrients on pharmacokinetic behavior of antiepileptic drugs after oral administration in rats. Fukuno, S; Hatsuda, Y; Iwanami, Y; Konishi, H; Myotoku, M; Nagai, K; Omotani, S; Ryuno, Y, 2021)	0.62
"We concluded that the pharmacokinetic profiles of CBZ, but not SVA and LEV, after its oral administration are affected by the dosing time of RASS, but staggered administration of CBZ and RASS prevented their interaction."	( Effects of concurrent and staggered dosing of semi-solid enteral nutrients on pharmacokinetic behavior of antiepileptic drugs after oral administration in rats. Fukuno, S; Hatsuda, Y; Iwanami, Y; Konishi, H; Myotoku, M; Nagai, K; Omotani, S; Ryuno, Y, 2021)	0.62
" We therefore aimed to explore levetiracetam pharmacokinetics and to propose its optimal dosing in the paediatric population."	( Levetiracetam pharmacokinetics and its covariates: proposal for optimal dosing in the paediatric population. Pokorná, P; Šíma, M; Slanař, O; Švestková, N, 2023)	0.91
" The determination of the CYP2C19 genotypes may be useful for dosing adjustment in schizophrenia patients on valproic acid therapy."	( Effect of CYP2C19 polymorphisms on serum valproic level acid in Chinese Han patients with schizophrenia. Ju, X; Li, J; Liu, J; Shi, J; Song, M; Wang, C; Wang, S; Yan, P, 2021)	0.83
" For developmental toxicity this requires scaling the in vitro observed dose-response characteristics to in vivo fetal exposure, while integrating maternal in vivo kinetics during pregnancy, in particular transplacental transfer."	( Integrating in vitro chemical transplacental passage into a generic PBK model: A QIVIVE approach. Fragki, S; Hoogenveen, R; Piersma, AH; Schwillens, P; van Oostrom, C; Zeilmaker, MJ, 2022)	0.72
"This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration."	( An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels. Adebayo, RA; Anıl Yağcıoğlu, AE; Arrojo-Romero, M; Ayub, M; Baptista, T; Bebawi, E; Bhattacharya, R; Bilbily, J; Bonelli, RM; Bousman, CA; Buckley, PF; Celofiga, A; Chan, SKW; Chopra, N; Citrome, L; Cohen, D; Correll, CU; Cotes, RO; Crespo-Facorro, B; Cubała, WJ; De Berardis, D; De Las Cuevas, C; de Leon, J; Decloedt, E; Eap, CB; Elkis, H; Ertuğrul, A; Every-Palmer, S; Farooq, S; Fernandez-Egea, E; Fountoulakis, KN; Freudenreich, O; González-Esquivel, DF; Grover, S; Gründer, G; Hiemke, C; Iglesias-Alonso, A; Iglesias-Garcia, C; Ignjatovic Ristic, D; Jung-Cook, H; Kaithi, AR; Kane, JM; Kelly, DL; Kim, SH; Kim, YS; Kirilochev, OO; Kopeček, M; Lana, F; Lane, HY; Lazary, J; Leung, JG; Lin, SK; LLerena, A; López-Jaramillo, C; Marder, SR; Masmoudi, R; McCollum, B; McGrane, I; Mohd Saffian, S; Molden, E; Motuca, M; Müller, DJ; Ng, CH; Nielsen, J; Olmos, I; Ortiz, BB; Otsuka, Y; Ouanes, S; Pacheco Palha, AJ; Pedro, MR; Procyshyn, RM; Quiles, C; Rădulescu, FŞ; Rajkumar, AP; Ricciardi, C; Rohde, C; Ruan, CJ; Sagud, M; Sanz, EJ; Schoretsanitis, G; Schulte, PFJ; Seifritz, E; Seppälä, N; Shelton, C; Silva, A; Siskind, D; Smith, RL; Solismaa, A; Soloviev, A; Spina, E; Švancer, P; Takeuchi, H; Tang, YL; Temmingh, H; Torres, R; Tsukahara, M; Verdoux, H; Villagrán-Moreno, JM; Wang, CY; Wang, G; Weizman, A; Wilkowska, A; Yecora, A; Zolezzi, M, 2022)	0.72
" No association was found between the incidence of coagulopathies and VPA dosage (mg/kg/day)."	( Assessment of need for hemostatic evaluation in patients taking valproic acid: A retrospective cross-sectional study. Beckers, EAM; Henskens, YMC; Heubel-Moenen, FCJI; Klinkenberg, S; Post, DS; Rijkers, K; Schijns, OEMG; van der Veer, A; van Kranen-Mastenbroek, VHJM; Verhezen, PWM; Wagner, GL; Willems, PCPH, 2022)	0.96
" LSTM shows better predictive performance to predict valproate plasma concentrations compared with a traditional pharmacometric model in the investigated setting with real-world data in older patients with epilepsy where information on exact timepoints for both dosing and plasma concentration measurement are missing."	( Artificial Neural Network vs. Pharmacometric Model for Population Prediction of Plasma Concentration in Real-World Data: A Case Study on Valproic Acid. Andersen, M; Lund, TM; Sessa, M; Soeorg, H; Sverrisdóttir, E, 2022)	0.92
" Hence, reducing VPA dosage to minimize side effects while maintaining its efficacy is necessary, and transcranial photobiomodulation (tPBM) add-on therapy could facilitate this."	( Transcranial photobiomodulation add-on therapy to valproic acid for pentylenetetrazole-induced seizures in peripubertal rats. Chang, H; Chang, SF; Tsai, CM, 2022)	0.97
" Pregnant C57BL/6 J mice were intraperitoneally injected with a dosage of 500 mg/kg valproic acid (VPA) on embryonic day 10."	( Size anomaly and alteration of GABAergic enzymes expressions in cerebellum of a valproic acid mouse model of autism. Kwan, KM; Ma, SY, 2022)	1.17
" If confirmed in further studies, a dosage of 25-30 mg/kg appears adequate in SE."	( Valproate in status epilepticus: Correlation between loading dose, serum levels, and clinical response. André, P; Buclin, T; Decosterd, LA; Novy, J; Rossetti, AO; Vijiala, S, 2022)	0.72
" We found that gestational VPA exposure via chronic maternal oral dosing was associated with substantial drug-induced differential gene expression in the pup brains, including dysregulated splicing, and observed that this occurred in the absence of evidence for significant neuronal gain or loss."	( Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability. Abouzeid, M; Feleke, R; Jazayeri, D; Johnson, MR; Jones, NC; O'Brien, TJ; Powell, KL; Srivastava, PK, 2022)	0.72
" Our model may be a useful tool for recommending dosage adjustments for physicians."	( Population pharmacokinetics and dosing optimization of olanzapine in Chinese paediatric patients: Based on the impact of sex and concomitant valproate on clearance. Hu, JQ; Huang, SQ; Kong, W; Li, XL; Liu, SJ; Lu, HQ; Lu, HY; Ni, XJ; Shang, DW; Wen, YG; Xiao, T; Yang, HL; Zhang, M; Zhu, XQ, 2022)	0.72
" This study adds new insights on this aspect, highlighting the safety of a tailored dosage of inositol in patients taking Li or VPA."	( Safety of inositol supplementation in patients taking lithium or valproic acid: a pilot clinical study. Cantelmi, T; Lepore, E; Unfer, V; Unfer, VR, 2022)	0.96
"This pilot study demonstrated that the dosage of 4 gr/daily of inositol is safe in patients taking Li/VPA, as we recorded no interference with the pharmacological therapy."	( Safety of inositol supplementation in patients taking lithium or valproic acid: a pilot clinical study. Cantelmi, T; Lepore, E; Unfer, V; Unfer, VR, 2022)	0.96
"Data on sex, age, and OLA dosage and steady-state plasma concentrations of 386 patients with schizophrenia (who have received OLA or a comedication of OLA with a psychotherapeutic drug) were collected and analyzed."	( Effects of Age, Sex, and Comedication on the Plasma Concentrations of Olanzapine in Chinese Patients With Schizophrenia Based on Therapeutic Drug Monitoring Data. Cui, X; Ding, J; Li, Y; Meng, Z; Xing, H; Yang, L; Zhang, S; Zhang, Y, )	0.13
" In drugs with well-known dose-response relationships, TDM can enhance patient outcomes and reduce health care costs."	( A Novel Approach for Therapeutic Drug Monitoring of Valproic Acid Using FT-IR Spectroscopy and Nonlinear Support Vector Regression. Bouatia, M; Cheikh, A; Cherrah, Y; El Abbes, FM; El Orche, A; Elhamdaoui, O; Jawhari, S; Johnson, JB; Mbarki, M, 2023)	1.16
" The dose required to reach 350ng/ml was considered the minimum therapeutic dosage and was used to classify patients according to clozapine PM status."	( Valproate, obesity and other causes of clozapine poor metabolism in the context of rapid titration may explain clozapine-induced myocarditis: A re-analysis of a Turkish case series. Ağaoğlu, E; Ak, S; Anıl Yağcıoğlu, AE; de Leon, J; Ertuğrul, A; Karakaşlı, AA; Yazıcı, MK, )	0.13
" Of the 10 patients, 9 had at least 1 of 3 factors: too-rapid titration in the first or second weeks, or a final dosage that was too high."	( Valproate, obesity and other causes of clozapine poor metabolism in the context of rapid titration may explain clozapine-induced myocarditis: A re-analysis of a Turkish case series. Ağaoğlu, E; Ak, S; Anıl Yağcıoğlu, AE; de Leon, J; Ertuğrul, A; Karakaşlı, AA; Yazıcı, MK, )	0.13
" VPM would require a closer dosing schedule and a 20% reduction in dosage when switching to valproate."	( Valproate, divalproex, valpromide: Are the differences in indications justified? Besson, VC; Blaise, N; Bloch, V; Chouchana, M; Delage, C; Etain, B; Hagenimana, M; Palayer, M; Smati, J, 2023)	0.91
" Male offsprings were injected with EPO and NEPO in a clinically proper postnatal dosing regimen on postnatal days (PND) 1-5, and autistic-like behaviors were tested at the end of the first month."	( The effects of postnatal erythropoietin and nano-erythropoietin on behavioral alterations by mediating K-Cl co-transporter 2 in the valproic acid-induced rat model of autism. Basiri, M; Darvishzadeh-Mahani, F; Haratizadeh, S; Nozari, M; Ranjbar, M, 2023)	1.11
" The purpose of this study was to establish a model for predicting the blood concentration of Li carbonate through an artificial neural network (ANN), and to provide a basis for the clinical rapid and effective formulation of individualized dosing regimens."	( The development and validation of a prediction model of lithium carbonate blood concentration by artificial neural network: a retrospective study. Feng, W; Hu, Z; Jing, Q; Li, J; Wang, Y; Zhang, J; Zhang, W, 2022)	0.72
" The QSP model was implemented to give a rational basis for the L-carnitine dose selection to optimize CS depending on VPA dosage regime and to assess the currently recommended L-carnitine rescue therapy after VPA overdosing."	( Quantitative systems pharmacology Model to characterize valproic acid-induced hyperammonemia and the effect of L-carnitine supplementation. Fagiolino, P; Ibarra, M; Maldonado, C; Schiavo, A; Trocóniz, IF; Vázquez, M, 2023)	1.16
" The data collected include demographic information, psychiatric diagnosis, comorbidities, liver function tests, serum ammonia and serum valproate levels, dosages and duration of valproate, management of hyperammonemia including dosage variations, discontinuation, adjuvant drugs used, and whether rechallenge was done."	( Valproate-Associated Hyperammonemic Encephalopathy: Clinical Correlates and Management Strategies in a Tertiary Care Center. Chatorikar, S; Munoli, RN; Praharaj, SK; Udupa, ST; Vaidyanathan, S, )	0.13
"This study was undertaken to determine the impact of dosage in new users of lamotrigine (LTG) and the concomitant intake of valproic acid (VPA) on epidermal necrolysis (EN)."	( Effects of dosage in new users of lamotrigine inducing epidermal necrolysis: Results of the German Registry of Severe Skin Reactions. Diederich, S; Hemmeter, U; Mockenhaupt, M; Paulmann, M, 2023)	1.12
" Evaluation of dosing regimen was restricted to cases with complete LTG dosing history (n = 74)."	( Effects of dosage in new users of lamotrigine inducing epidermal necrolysis: Results of the German Registry of Severe Skin Reactions. Diederich, S; Hemmeter, U; Mockenhaupt, M; Paulmann, M, 2023)	0.91
" Our comparative analysis suggests DOAC plasma concentration monitoring as a possible strategy to guide dosing owing to the predictable correlation between DOACs' plasma concentration and effect."	( Interactions Between Direct Oral Anticoagulants (DOACs) and Antiseizure Medications: Potential Implications on DOAC Treatment. Bialer, M; Goldstein, R; Gronich, N; Jacobs, AR; Muszkat, M; Zighan, L, 2023)	0.91
" The repetitive behaviors were ameliorated relatively in VPA groups with NEPO2000 treatment, and astrogliosis was reduced even when VPA rats were treated with a lower dosage of NEPO."	( Astrocyte responses to postnatal erythropoietin and nano-erythropoietin treatments in a valproic acid-induced animal model of autism. Basiri, M; Haratizadeh, S; Nozari, M; Ranjbar, M, 2023)	1.13
" The present study explored the pharmacokinetics (PK) and exposure safety of DP-VPA to provide a basis for future studies exploring the safe dosage and therapeutic strategies for epilepsy."	( Population pharmacokinetics and exposure-safety of lipophilic conjugates prodrug DP-VPA in healthy Chinese subjects for dose regime exploring. Cao, G; Chen, Y; Fan, Y; Guo, B; Hu, J; Li, X; Li, Y; Liu, X; Wang, Y; Wu, H; Wu, J; Wu, X; Xu, X; Yu, J; Yu, P; Zhan, H; Zhang, J, 2023)	0.91
" This study aimed to characterize the initial monotherapy ethosuximide exposure-response relationship and to propose model-informed precision dosing guidance."	( Model-Informed Precision Dosing Guidance of Ethosuximide Developed from a Randomized Controlled Clinical Trial of Childhood Absence Epilepsy. Adamson, PC; Blumer, JL; Capparelli, EV; Clark, PO; Cnaan, A; Dong, M; Fukuda, T; Glauser, TA; Mizuno, K; Reed, MD; Shinnar, S; Vinks, AA, 2023)	0.91
" Hyperammonemia was more common in patients with higher VPA dosage and higher total drug loads of concurrent antiseizure medications (ASMs)."	( Risk factors of hyperammonemia in epilepsy patients with valproic acid therapy. Kim, DW; Kwack, DW, 2023)	1.16
"The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA."	( Association of clozapine and norclozapine levels with patient and therapy characteristics-focus on interaction with valproic acid. Jovanović, M; Lukić, V; Miljković, B; Milovanović, S; Panić, B; Vučićević, K, 2023)	1.12
"97%), switching to or adjusting carbamazepine dosage (27."	( The impact of a newly established specialized pediatric epilepsy center in Tanzania: An observational study. Aricò, M; Di Noia, SP; Kalolo, A; Mabusi, MS; Mastrangelo, M; Pisani, F, 2023)	0.91