Trial reportHuman genomics2008
Influence of SLCO1B1 and CYP2C8 gene polymorphisms on rosiglitazone pharmacokinetics in healthy volunteers.
Trial report in Human genomics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
19 citing papers in PubMed, 53 citations in OpenAlex.
- Impact of the CYP2C8 *3 polymorphism on the drug-drug interaction between gemfibrozil and pioglitazone.British journal of clinical pharmacology · 2013Trial
- Pharmacogenetic analysis of inter-ethnic variability in the uptake transporter SLCO1B1 gene in Colombian, Mozambican, and Portuguese populations.BMC medical genomics · 2023Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Pharmacogenomic Studies of Current Antidiabetic Agents and Potential New Drug Targets for Precision Medicine of Diabetes.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2020Review
- Challenges to assess substrate-dependent allelic effects in CYP450 enzymes and the potential clinical implications.The pharmacogenomics journal · 2019Review
- 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
- Pharmacogenetics of Antidiabetic Drugs.Advances in pharmacology (San Diego, Calif.) · 2018Review
- In vitro metabolism of exemestane by hepatic cytochrome P450s: impact of nonsynonymous polymorphisms on formation of the active metabolite 17Pharmacology research & perspectives · 2017Article
- The influence ofBalkan journal of medical genetics : BJMG · 2016Article
- Pharmacogenetics in type 2 diabetes: influence on response to oral hypoglycemic agents.Pharmacogenomics and personalized medicine · 2016Review
- PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 8.Pharmacogenetics and genomics · 2013Review
- The role of pharmacogenetics in drug disposition and response of oral glucose-lowering drugs.Clinical pharmacokinetics · 2013Review
- 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
- Individualized therapy for type 2 diabetes: clinical implications of pharmacogenetic data.Molecular diagnosis & therapy · 2012Review
- Mild hypoglycaemic attacks induced by sulphonylureas related to CYP2C9, CYP2C19 and CYP2C8 polymorphisms in routine clinical setting.European journal of clinical pharmacology · 2011Article
- Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity.The pharmacogenomics journal · 2011Article
- Pharmacogenetics of Anti-Diabetes Drugs.Pharmaceuticals (Basel, Switzerland) · 2010Article
- Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.Pharmacogenomics · 2009Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Polymorphisms in drug transporter genes and/or drug-metabolising enzyme genes may contribute to inter-individual variability in rosiglitazone pharmacokinetics in humans. We sought to determine the joint effects of polymorphisms in the SLCO1B1 drug transporter gene and the cytochrome P450 ( CYP ) 2C8-metabolising enzyme gene on rosiglitazone pharmacokinetics in healthy volunteers. Healthy Caucasian subjects were prospectively enrolled on the basis of SLCO1B1 521 T > C genotype. Additionally, subjects were genotyped for SLCO1B1 -11187 G > A, -10499 A > C and 388 A > G polymorphisms, and the CYP2C8*3 polymorphism. SLCO1B1 haplotypes and diplotypes were computationally assigned. Rosiglitazone plasma concentrations were determined by high-performance liquid chromatography and analysed using non-compartmental methods. The study population consisted of 26 subjects, with a mean age of 33 +/- 9 years, and a mean weight of 66.6 +/- 11.7 kg. There were no significant differences in rosiglitazone pharmacokinetic parameters between SLCO1B1 diplotype groups. Subjects with the CYP2C8*1/*3 genotype ( n = 7), however, had significantly lower rosiglitazone area under the plasma concentration-time curve (AUC) and significantly higher rosiglitazone oral clearance, compared with CYP2C8 wild-type homozygotes ( n = 19). Stepwise linear regression analysis revealed that CYP2C8 genotype ( p = 0.006) and weight ( p = 0.022) were significant predictors of rosiglitazone AUC (overall p = 0.002; R 2 = 41.6 per cent). We concluded that polymorphisms in the CYP2C8 drug-metabolising enzyme gene, but not the SLCO1B1 drug transporter gene, significantly influence rosiglitazone disposition in humans. Future studies examining the influence of CYP2C8 genotypes and haplotypes on thiazolidinedione disposition and response in patients with type 2 diabetes are warranted.
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