ArticleThe pharmacogenomics journal2003
Influence of CYP2C9 genotypes on the formation of a hepatotoxic metabolite of valproic acid in human liver microsomes.
Article in The pharmacogenomics journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Influence of CYP2C9 and CYP2A6 on plasma concentrations of valproic acid: a meta-analysis.European journal of clinical pharmacology · 2020Pooled it
- CYP2C9*3 allelic variant is associated with metabolism of irbesartan in Chinese population.European journal of clinical pharmacology · 2005Trial
- Reconstructing the pharmacogenomic landscape of psychiatric medication metabolism in the Indian population.Communications medicine · 2026Article
- Drug metabolizing enzymes and transporters, and their roles for the development of drug-induced liver injury.Expert opinion on drug metabolism & toxicology · 2025Review
- Physiologically-Based Pharmacokinetic Modeling of Total and Unbound Valproic Acid to Evaluate Dosing in Children With and Without Hypoalbuminemia.Clinical pharmacokinetics · 2024Article
- Structural and biophysical analysis of cytochrome P450 2C9*14 and *27 variants in complex with losartan.Journal of inorganic biochemistry · 2024Article
- Ethnic Aspects of Valproic Acid P-Oxidation.Biomedicines · 2024Review
- PAMAM-G4 protect the N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) and maintain its antiproliferative effects on MCF-7.Scientific reports · 2023Article
- Machine learning advances the integration of covariates in population pharmacokinetic models: Valproic acid as an example.Frontiers in pharmacology · 2022Article
- Impact of genetic and non-genetic factors on hepatic CYP2C9 expression and activity in Hungarian subjects.Scientific reports · 2021Article
- Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Human Family 1-4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update.Archives of toxicology · 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
- Personalized Medicine Using Cutting Edge Technologies for Genetic Epilepsies.Current neuropharmacology · 2021Review
- Structure of Cytochrome P450 2C9*2 in Complex with Losartan: Insights into the Effect of Genetic Polymorphism.Molecular pharmacology · 2020Article
- Clinical Relevance of Pharmacogenetics in Serotonin Syndrome.Case reports in psychiatry · 2020Article
- Functional Measurement of CYP2C9 and CYP3A4 Allelic Polymorphism on Sildenafil Metabolism.Drug design, development and therapy · 2020Article
- Estimation of apparent clearance of valproic acid in adult Saudi patients.International journal of clinical pharmacy · 2019Article
- Relevance of CYP2C9 Function in Valproate Therapy.Current neuropharmacology · 2019Review
- 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
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The present study investigated the effect of cytochrome P450 2C9 (CYP2C9) genetic polymorphism on the biotransformation of valproic acid (VPA) to its hepatotoxic metabolite, 4-ene-VPA, and compared that to the formation of the inactive 4-OH-VPA and 5-OH-VPA. cDNA-expressed CYP2C9(*)2 and CYP2C9(*)3 variants were less efficient than the CYP2C9(*)1 wild type in catalyzing the formation of these metabolites, as assessed by the ratio of Vmax and apparent Km (in vitro intrinsic clearance). The reduced efficiency by CYP2C9(*)2 was due to a reduced Vmax, whereas, in the case of CYP2C9(*)3, it was the result of increased apparent Km. The formation rates of 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA in human liver microsomes were reduced by 29, 28, and 31%, respectively, in samples with one mutated CYP2C9 allele, and by 61, 73, and 58%, respectively, in samples with two mutated CYP2C9 alleles. Overall, the homozygote and heterozygote CYP2C9(*)2 and CYP2C9(*)3 genotypes may compromise hepatic VPA biotransformation.
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