Trial reportBritish journal of clinical pharmacology2005
The effect of trimethoprim on CYP2C8 mediated rosiglitazone metabolism in human liver microsomes and healthy subjects.
Trial report in British journal of clinical pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Improving antibacterial prescribing safety in the management of COPD exacerbations: systematic review of observational and clinical studies on potential drug interactions associated with frequently prescribed antibacterials among COPD patients.The Journal of antimicrobial chemotherapy · 2019Pooled it
- The drug interaction potential of daprodustat when coadministered with pioglitazone, rosuvastatin, or trimethoprim in healthy subjects.Pharmacology research & perspectives · 2018Trial
- Effect of multiple doses of montelukast on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in humans.British journal of clinical pharmacology · 2007Trial
- Lack of pharmacokinetic interaction for ISIS 113715, a 2'-0-methoxyethyl modified antisense oligonucleotide targeting protein tyrosine phosphatase 1B messenger RNA, with oral antidiabetic compounds metformin, glipizide or rosiglitazone.Clinical pharmacokinetics · 2006Trial
- Nutrient environment improves drug metabolic activity in human iPSC-derived hepatocytes and HepG2.Archives of toxicology · 2025Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Drug metabolism and drug transport of the 100 most prescribed oral drugs.Basic & clinical pharmacology & toxicology · 2022Review
- Pharmacokinetics and Pharmacodynamics of Ibrexafungerp.Drugs in R&D · 2022Review
- Pharmacogenomics and Personalized Medicine in Type 2 Diabetes Mellitus: Potential Implications for Clinical Practice.Pharmacogenomics and personalized medicine · 2021Review
- Mechanistic in vitro studies confirm that inhibition of the renal apical efflux transporter multidrug and toxin extrusion (MATE) 1, and not altered absorption, underlies the increased metformin exposure observed in clinical interactions with cimetidine, trimethoprim or pyrimethamine.Pharmacology research & perspectives · 2017Article
- Rosiglitazone Metabolism in Human Liver Microsomes Using a Substrate Depletion Method.Drugs in R&D · 2017Article
- Personalized medicine in diabetes mellitus: current opportunities and future prospects.Annals of the New York Academy of Sciences · 2015Review
- Effects of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) on Pharmacokinetic Parameters of Rosiglitazone in Healthy Subjects.Clinical pharmacology in drug development · 2015Article
- Review
- 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
- Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity.European journal of drug metabolism and pharmacokinetics · 2011Review
- Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.Pharmacogenomics · 2009Article
- Pharmacokinetic interactions with thiazolidinediones.Clinical pharmacokinetics · 2007Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
aimsRosiglitazone, a thiazolidinedione antidiabetic medication used in the treatment of Type 2 diabetes mellitus, is predominantly metabolized by the cytochrome P450 (CYP) enzyme CYP2C8. The anti-infective drug trimethoprim has been shown in vitro to be a selective inhibitor of CYP2C8. The purpose of this study was to evaluate the effect of trimethoprim on the CYP2C8 mediated metabolism of rosiglitazone in vivo and in vitro.
methodsThe effect of trimethoprim on the metabolism of rosiglitazone in vitro was assessed in pooled human liver microsomes. The effect in vivo was determined by evaluating rosiglitazone pharmacokinetics in the presence and absence of trimethoprim. Eight healthy subjects (four men and four women) completed a randomized, cross-over study. Subjects received single dose rosiglitazone (8 mg) in the presence and absence of trimethoprim 200 mg given twice daily for 5 days.
resultsTrimethoprim inhibited rosiglitazone metabolism both in vitro and in vivo. Inhibition of rosiglitazone para-hydroxylation by trimethoprim in vitro was found to be competitive with apparent K(i) and IC(50) values of 29 microm and 54.5 microm, respectively. In the presence of trimethoprim, rosiglitazone plasma AUC was increased by 31% (P = 0.01) from 2774 +/- 645 microg l(-1) h to 3643 +/- 1051 microg l(-1) h (95% confidence interval (CI) for difference 189, 1549), and half-life was increased by 27% (P = 0.006) from 3.3 +/- 0.5 to 4.2 +/- 0.8 h (95% CI for difference 0.36, 1.5). Trimethoprim reduced the para-O-sulphate rosiglitazone/rosiglitazone and the N-desmethylrosiglitazone/rosiglitazone AUC(0-24) ratios by 22% and 38%, respectively.
conclusionsThese results indicate that trimethoprim is a competitive inhibitor of CYP2C8-mediated rosiglitazone metabolism in vitro and that trimethoprim administration increases plasma rosiglitazone concentrations in healthy subjects.
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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.