ArticlePharmaceutical research2009
Prediction of the effects of genetic polymorphism on the pharmacokinetics of CYP2C9 substrates from in vitro data.
Article in Pharmaceutical research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.
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Who cites it
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update.Clinical pharmacology and therapeutics · 2021Guideline
- Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs.Clinical pharmacology and therapeutics · 2020Guideline
- CYP2B6 pharmacogenetics-based in vitro-in vivo extrapolation of efavirenz clearance by physiologically based pharmacokinetic modeling.Drug metabolism and disposition: the biological fate of chemicals · 2013Trial
- A Digital Twin of the Angiotensin II Receptor Blocker Losartan: Physiologically Based Modeling of Blood Pressure Regulation.Pharmaceutics · 2026Article
- The Role of Pharmacogenetic Biomarkers in Pain.Biomedicines · 2025Article
- Effects of genetic polymorphism of drug-metabolizing enzymes on the plasma concentrations of antiepileptic drugs in Chinese population.Bioengineered · 2022Review
- Comprehensive PBPK Model of Rifampicin for Quantitative Prediction of Complex Drug-Drug Interactions: CYP3A/2C9 Induction and OATP Inhibition Effects.CPT: pharmacometrics & systems pharmacology · 2018Article
- Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2015Article
- Application of in vitro-in vivo extrapolation (IVIVE) and physiologically based pharmacokinetic (PBPK) modelling to investigate the impact of the CYP2C8 polymorphism on rosiglitazone exposure.European journal of clinical pharmacology · 2013Article
- Article
- Cytochrome P450 2C9-CYP2C9.Pharmacogenetics and genomics · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe *2 and *3 alleles of CYP2C9, with decreased enzymatic activity, are highly polymorphic and contribute to inter-individual differences in pharmacotherapy of CYP2C9 substrates. Here, we sought for a simplified theoretical method to predict the pharmacokinetic changes with minimal in vivo data.
methodsThe changes in clearances of CYP2C9 substrates in subjects with these alleles were quantitatively estimated by parameters from literature data: intrinsic metabolic clearance and the enzyme expression level of mutated CYP2C9, contribution of CYP2C9 to the CYP-mediated clearance (f (m2C9)), and the contribution of the dominant metabolic pathways to the total clearance (f (h)). To validate the accuracy of our prediction, the changes were compared to reported in vivo values.
resultsSufficient data were available for nine substrates: celecoxib, diclofenac, S-flurbiprofen, losartan, S-phenprocoumon, phenytoin, tolbutamide, torsemide, and S-warfarin. These predicted values, either using the intrinsic clearance specific to each substrate, or the averaged values (*2: 0.66, *3: 0.13, (ratio to *1)), correlated well with observed values (r (2) = 0.812, 0.786, respectively).
conclusionsThis theoretical method well estimated the quantitative changes in pharmacokinetics of CYP2C9 substrates in subjects with mutated alleles of CYP2C9. This can be applied to drug development even from the early clinical phases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.