Trial reportBritish journal of clinical pharmacology2013
Impact of the CYP2C8 *3 polymorphism on the drug-drug interaction between gemfibrozil and pioglitazone.
Trial report in British journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Meta-analysis of the global distribution of clinically relevant CYP2C8 alleles and their inferred functional consequences.Human genomics · 2024Pooled it
- Clopidogrel but Not Prasugrel Significantly Inhibits the CYP2C8-Mediated Metabolism of Montelukast in Humans.Clinical pharmacology and therapeutics · 2018Trial
- Influence of CYP2C8*2 on the pharmacokinetics of pioglitazone in healthy African-American volunteers.Pharmacotherapy · 2013Trial
- Genetic and Non-genetic Correlates of Imatinib Pharmacokinetics and Side Effects of Imatinib in Palestinian Patients with Chronic Myeloid Leukemia.Biochemical genetics · 2026Article
- CYP2C8-Mediated Drug-Drug Interactions and the Factors Influencing the Interaction Magnitude.Drug design, development and therapy · 2025Review
- Influence of CYP2C8*3 and ABCG2 C421A genetic polymorphisms on trough concentration and molecular response of imatinib in Egyptian patients with chronic myeloid leukemia.Cancer chemotherapy and pharmacology · 2024Article
- Drug metabolism and drug transport of the 100 most prescribed oral drugs.Basic & clinical pharmacology & toxicology · 2022Review
- Variability of CYP2C8 Polymorphisms in Three Jordanian Populations: Circassians, Chechens and Jordanian-Arabs.Journal of immigrant and minority health · 2022Article
- Clopidogrel, a CYP2C8 inhibitor, causes a clinically relevant increase in the systemic exposure to the active metabolite of selexipag in healthy subjects.British journal of clinical pharmacology · 2021Article
- Challenges to assess substrate-dependent allelic effects in CYP450 enzymes and the potential clinical implications.The pharmacogenomics journal · 2019Review
- Use of Physiologically Based Pharmacokinetic Modeling to Evaluate the Effect of Chronic Kidney Disease on the Disposition of Hepatic CYP2C8 and OATP1B Drug Substrates.Clinical pharmacology and therapeutics · 2019Article
- Pharmacogenetics of type 2 diabetes mellitus, the route toward tailored medicine.Diabetes/metabolism research and reviews · 2019Review
- Patients carrying CYP2C8*3 have shorter systemic paclitaxel exposure.Pharmacogenomics · 2019Article
- A Genetic Score Associates With Pioglitazone Response in Patients With Non-alcoholic Steatohepatitis.Frontiers in pharmacology · 2018Article
- Rosiglitazone Metabolism in Human Liver Microsomes Using a Substrate Depletion Method.Drugs in R&D · 2017Article
- Projecting ADME Behavior and Drug-Drug Interactions in Early Discovery and Development: Application of the Extended Clearance Classification System.Pharmaceutical research · 2016Article
- Quantitative Prediction of Drug-Drug Interactions Involving Inhibitory Metabolites in Drug Development: How Can Physiologically Based Pharmacokinetic Modeling Help?CPT: pharmacometrics & systems pharmacology · 2016Article
- Pharmacogenetics in type 2 diabetes: influence on response to oral hypoglycemic agents.Pharmacogenomics and personalized medicine · 2016Review
- A stewardship intervention program for safe medication management and use of antidiabetic drugs.Clinical interventions in aging · 2015Article
- Pharmacogenomics and pharmacogenetics of thiazolidinediones: role in diabetes and cardiovascular risk factors.Pharmacogenomics · 2014Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
aimThe objective of this study was to determine the extent to which the CYP2C8*3 allele influences pharmacokinetic variability in the drug-drug interaction between gemfibrozil (CYP2C8 inhibitor) and pioglitazone (CYP2C8 substrate).
methodsIn this randomized, two phase crossover study, 30 healthy Caucasian subjects were enrolled based on CYP2C8*3 genotype (n = 15, CYP2C8*1/*1; n = 15, CYP2C8*3 carriers). Subjects received a single 15 mg dose of pioglitazone or gemfibrozil 600 mg every 12 h for 4 days with a single 15 mg dose of pioglitazone administered on the morning of day 3. A 48 h pharmacokinetic study followed each pioglitazone dose and the study phases were separated by a 14 day washout period.
resultsGemfibrozil significantly increased mean pioglitazone AUC(0,∞) by 4.3-fold (P < 0.001) and there was interindividual variability in the magnitude of this interaction (range, 1.8- to 12.1-fold). When pioglitazone was administered alone, the mean AUC(0,∞) was 29.7% lower (P = 0.01) in CYP2C8*3 carriers compared with CYP2C8*1 homozygotes. The relative change in pioglitazone plasma exposure following gemfibrozil administration was significantly influenced by CYP2C8 genotype. Specifically, CYP2C8*3 carriers had a 5.2-fold mean increase in pioglitazone AUC(0,∞) compared with a 3.3-fold mean increase in CYP2C8*1 homozygotes (P = 0.02).
conclusionCYP2C8*3 is associated with decreased pioglitazone plasma exposure in vivo and significantly influences the pharmacokinetic magnitude of the gemfibrozil-pioglitazone drug-drug interaction. Additional studies are needed to evaluate the impact of CYP2C8 genetics on the pharmacokinetics of other CYP2C8-mediated drug-drug interactions.
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