ArticleEuropean journal of clinical pharmacology2009
Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients: nonlinear mixed-effect modeling.
Article in European journal of clinical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- A systematic review of population pharmacokinetics of valproic acid.British journal of clinical pharmacology · 2018Pooled it
- Sex related differences on valproic acid pharmacokinetics after oral single dose.Journal of pharmacokinetics and pharmacodynamics · 2013Trial
- Population pharmacokinetics of valproic acid in pediatric patients with epilepsy: considerations for dosing spinal muscular atrophy patients.Journal of clinical pharmacology · 2012Trial
- Virtual Twin Approach Using Physiologically Based Pharmacokinetic Modeling to Support Precision Dosing of Valproic Acid in Geriatric Patients.Clinical pharmacology and therapeutics · 2026Article
- Exploring the Pharmacokinetics of Drugs in Disabled Saudi Patients: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Fixed parameters in the population pharmacokinetic modeling of valproic acid might not be suitable: external validation in Chinese adults with epilepsy or after neurosurgery.European journal of clinical pharmacology · 2024Article
- Modeling the protein binding non-linearity in population pharmacokinetic model of valproic acid in children with epilepsy: a systematic evaluation study.Frontiers in pharmacology · 2023Article
- Impact of CYP2C19 and CYP2C9 gene polymorphisms on sodium valproate plasma concentration in patients with epilepsy.European journal of hospital pharmacy : science and practice · 2022Article
- Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian Patients.Pharmaceutics · 2022Article
- Population pharmacokinetics of valproic acid in adult Chinese patients with bipolar disorder.European journal of clinical pharmacology · 2022Article
- Machine learning advances the integration of covariates in population pharmacokinetic models: Valproic acid as an example.Frontiers in pharmacology · 2022Article
- Comparative pharmacokinetics of valproic acid among Pakistani and South Korean patients: A population pharmacokinetic study.PloS one · 2022Article
- Effect of CYP2C19 polymorphisms on serum valproic level acid in Chinese Han patients with schizophrenia.Scientific reports · 2021Article
- Valproic acid autoinduction: a case-based review.International journal of bipolar disorders · 2021Review
- The association of adjusted plasma valproic acid concentration withAnnals of translational medicine · 2021Article
- CYP2C9*3/*3 Gene Expression Affects the Total and Free Concentrations of Valproic Acid in Pediatric Patients with Epilepsy.Pharmacogenomics and personalized medicine · 2021Article
- Impact of gender, albumin, and CYP2C19 polymorphisms on valproic acid in Chinese patients: a population pharmacokinetic model.The Journal of international medical research · 2020Article
- Genetic and Non-genetic Factors Contributing to the Significant Variation in the Plasma Trough Concentration-to-Dose Ratio of Valproic Acid in Children With Epilepsy.Frontiers in pediatrics · 2020Article
- Estimation of apparent clearance of valproic acid in adult Saudi patients.International journal of clinical pharmacy · 2019Article
- Effect of CYP2C19, UGT1A8, and UGT2B7 on valproic acid clearance in children with epilepsy: a population pharmacokinetic model.European journal of clinical pharmacology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo 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.
methodsVPA concentrations were measured in 287 epileptic patients, who were genotyped for CYP2C19*2/*3 and CYP2C9*3. Patients who were on monotherapy with VPA were divided into two groups, a PPK-model group (n = 177) and a PPK-valid group (n = 110). The PPK parameter values for VPA were calculated in the PPK-model group by using the NONMEM software. Ultimately, a biological model and a final model were established. Each model was then used to independently predict the concentrations of the PPK-valid group to validate the two models.
resultsThere was a significant effect of the CYP2C19 and CYP2C9 genotypes on the pharmacokinetic (PK) variability (P < 0.01) in the final PPK model of CL/F. The interindividual CL was calculated according to the final model: CL/F = 0.0951 x (1 + e(0.0267 x (3 - genotype))) + 0.0071 x age (L/h). The coefficient of variation (CV) (omega CL/F) of the final model was 29.3%, while that of the biological model was 31.7%. Based on the genotype, the individual PK parameters can be calculated more accurately than before.
conclusionThe CYP2C19 and CYP2C9 genotypes significantly influenced the PK variability of VPA, as quantified by NONMEM software.
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