ArticleEuropean journal of clinical pharmacology2018
Effect of CYP2C19, UGT1A8, and UGT2B7 on valproic acid clearance in children with epilepsy: a population pharmacokinetic model.
Article in European journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Dosing prediction of valproic acid in pediatric patients with epilepsy: population pharmacokinetic model or machine learning model?European journal of clinical pharmacology · 2025Article
- Prediction Trough Concentrations of Valproic Acid Among Chinese Adult Patients with Epilepsy Using Machine Learning Techniques.Pharmaceutical research · 2025Article
- 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
- Population pharmacokinetics of valproic acid in children with epilepsy: Implications for dose tailoring when switching from oral syrup to sustained-release tablets.CPT: pharmacometrics & systems pharmacology · 2024Article
- Sources of pharmacokinetic and pharmacodynamic variability and clinical pharmacology studies of antiseizure medications in the pediatric population.Clinical and translational science · 2024Review
- Evaluation ofPharmacogenomics and personalized medicine · 2024Article
- Population pharmacokinetics of oxcarbazepine active metabolite in Chinese children with epilepsy.European journal of pediatrics · 2023Article
- Population pharmacokinetics of topiramate in Chinese children with epilepsy.European journal of clinical pharmacology · 2023Article
- Pharmacogenetic Aspects of Drug Metabolizing Enzymes and Transporters in Pediatric Medicine: Study Progress, Clinical Practice and Future Perspectives.Paediatric drugs · 2023Review
- Joint use of population pharmacokinetics and machine learning for optimizing antiepileptic treatment in pediatric population.Therapeutic advances in drug safety · 2023Article
- 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
- Population pharmacokinetics of valproic acid in adult Chinese patients with bipolar disorder.European journal of clinical pharmacology · 2022Article
- Pharmacogenetics-based population pharmacokinetic analysis and dose optimization of valproic acid in Chinese southern children with epilepsy: Effect ofFrontiers in pharmacology · 2022Article
- Effect of CYP2C19 polymorphisms on serum valproic level acid in Chinese Han patients with schizophrenia.Scientific reports · 2021Article
- Factors Influencing Sodium Valproate Serum Concentrations in Patients with Epilepsy Based on Logistic Regression Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Impact of gender, albumin, and CYP2C19 polymorphisms on valproic acid in Chinese patients: a population pharmacokinetic model.The Journal of international medical research · 2020Article
- Lack of association between valproic acid response and polymorphisms of its metabolism, transport, and receptor genes in children with focal seizures.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeValproic acid (VPA) is an important drug in seizure control with great inter-individual differences in metabolism and treatment effect. This study aims to identify the effects of genetic variants on VPA clearance in a population pharmacokinetic (popPK) model in children with epilepsy.
methodsA total of 325 VPA plasma concentrations from 290 children with epilepsy were used to develop the popPK model by using the nonlinear mixed-effects modeling method. The one-compartment model was established to describe the pharmacokinetics of VPA. Twelve single nucleotide polymorphisms involved in the pharmacokinetics of VPA were identified by MassARRAY system and their effects on VPA clearance were evaluated.
resultsIn the two final popPK models, inclusion of a combined genotype of four variants (rs1042597, rs28365062, rs4986893, and rs4244285), total daily dose (TDD), and body surface area (BSA) significantly reduced inter-individual variability for clearance over the base model. The inter-individual clearance equals to 0.73 × (TDD/628.92)
conclusionTDD, BSA, and genotype might affect VPA clearance in children. The popPK models may be useful for dosing adjustment in children on VPA therapy.
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