ArticleEuropean journal of clinical pharmacology2016
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.
Article in European journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Pharmacogenetic Variants and Plasma Concentrations of Antiseizure Drugs: A Systematic Review and Meta-Analysis.JAMA network open · 2024Pooled it
- Investigation of the Roles of New Antiepileptic Drugs and Serum BDNF Levels in Efficacy and Safety Monitoring and Quality of Life: A Clinical Research.Current clinical pharmacology · 2020Trial
- Machine Learning for Valproic Acid Therapy: A Scoping Review of Pharmacokinetic-Prediction Models and Pharmacokinetic-Informed Clinical Outcome Models.Pharmaceutics · 2026Review
- Association BetweenPharmaceuticals (Basel, Switzerland) · 2025Article
- Valproic acid levels in neurodevelopmental disorders: correlation with CYP and SULT genes using LC-MS/MS.BMC neurology · 2025Article
- 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
- Evaluation ofPharmacogenomics and personalized medicine · 2024Article
- A 5-Year Study of Lithium and Valproic Acid Drug Monitoring in Patients with Bipolar Disorders in an Italian Clinical Center.Pharmaceuticals (Basel, Switzerland) · 2022Article
- The association of adjusted plasma valproic acid concentration withAnnals of translational medicine · 2021Article
- Clinical pharmacogenomics in action: design, assessment and implementation of a novel pharmacogenetic panel supporting drug selection for diseases of the central nervous system (CNS).Journal of translational medicine · 2021Article
- Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters.Pharmaceuticals (Basel, Switzerland) · 2021Review
- 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
- Pharmacogenomic Characterization in Bipolar Spectrum Disorders.Pharmaceutics · 2019Review
- Estimation of apparent clearance of valproic acid in adult Saudi patients.International journal of clinical pharmacy · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeValproic acid (VPA) has an extensive interindividual pharmacokinetic variability. Published data regarding the impact of gender, age, and CYP2C9/2C19 genetics on VPA variability are conflicting, and the purpose of present study is to clarify the effect of these factors on dose-adjusted steady-state serum VPA concentration (C:D ratio) in a large, naturalistic patient material.
methodsIn patients who had been subjected to cytochrome P450 (CYP) genotyping and therapeutic drug monitoring of VPA, information about serum concentrations, dose, gender, age, and CYP2C9/2C19 genotypes was retrospectively collected from a routine TDM database during the period 2008-2012. The effects of age, gender, and CYP2C9/CYP2C19 genotypes on C:D ratios of VPA were investigated by multivariate analyses (mixed model) including sampling time as covariate.
resultsIn total, 857 serum concentrations from 252 patients were included. A significant gender effect was observed with a 1.3-fold higher estimated C:D ratio in females than in males, i.e., geometric means 0.34 vs. 0.27 μM/mg/day, respectively (p < 0.001). A similar and significant difference in estimated geometric means was found between patients >65 vs. ≤65 years, i.e., 0.36 vs. 0.26 μM/mg/day (p < 0.001), respectively. Finally, no association between the various CYP2C9/2C19 variant genotypes and C:D ratio of VPA was observed (p > 0.1).
conclusionThe present study shows that age and gender significantly influence VPA serum concentration. 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. Moreover, we conclude that CYP2C9/2C19 genotype is not relevant for variability in VPA exposure.
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