ArticleThe pharmacogenomics journal2016
Interindividual variability of CYP2C19-catalyzed drug metabolism due to differences in gene diplotypes and cytochrome P450 oxidoreductase content.
Article in The pharmacogenomics journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
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- Physiologically based pharmacokinetic (PBPK) modeling of gliclazide for different genotypes of CYP2C9 and CYP2C19.Archives of pharmacal research · 2025Article
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- Probing Liver Injuries Induced by Thioacetamide in Human In Vitro Pooled Hepatocyte Experiments.International journal of molecular sciences · 2024Article
- Cytochrome P450 FamilyACS pharmacology & translational science · 2024Article
- The polygenic implication of clopidogrel responsiveness: Insights from platelet reactivity analysis and next-generation sequencing.PloS one · 2024Article
- The Utility of Mixed Effects Models in the Evaluation of Complex Genomic Traits In Vitro.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
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- Development of Physiology Based Pharmacokinetic Model to Predict the Drug Interactions of Voriconazole and Venetoclax.Pharmaceutical research · 2022Article
- Quantitative Proteomics in Translational Absorption, Distribution, Metabolism, and Excretion and Precision Medicine.Pharmacological reviews · 2022Review
- Impact of polymorphisms of pharmacokinetics-related genes and the inflammatory response on the metabolism of voriconazole.Pharmacology research & perspectives · 2022Article
- Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach.British journal of clinical pharmacology · 2022Article
- Effect of major CYP2C19 genetic polymorphisms onBiomedical reports · 2022Article
- Characterization of CYP3A pharmacogenetic variation in American Indian and Alaska Native communities, targeting CYP3A4*1G allele function.Clinical and translational science · 2021Observational
- Prevalence of five pharmacologically most importantArhiv za higijenu rada i toksikologiju · 2021Article
- In Vivo Functional Effects ofDrug metabolism and disposition: the biological fate of chemicals · 2021Article
- Characterization of primary mouse hepatocyte spheroids as a model system to support investigations of drug-induced liver injury.Toxicology in vitro : an international journal published in association with BIBRA · 2021Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Large interindividual variability has been observed in the metabolism of CYP2C19 substrates in vivo. The study aimed to evaluate sources of this variability in CYP2C19 activity, focusing on CYP2C19 diplotypes and the cytochrome P450 oxidoreductase (POR). CYP2C19 gene analysis was carried out on 347 human liver samples. CYP2C19 activity assayed using human liver microsomes confirmed a significant a priori predicted rank order for (S)-mephenytoin hydroxylase activity of CYP2C19*17/*17 > *1B/*17 > *1B/*1B > *2A/*17 > *1B/*2A > *2A/*2A diplotypes. In a multivariate analysis, the CYP2C19*2A allele and POR protein content were associated with CYP2C19 activity. Further analysis indicated a strong effect of the CYP2C19*2A, but not the *17, allele on both metabolic steps in the conversion of clopidogrel to its active metabolite. The present study demonstrates that interindividual variability in CYP2C19 activity is due to differences in both CYP2C19 protein content associated with gene diplotypes and the POR concentration.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.58.
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