Trial reportBritish journal of clinical pharmacology2004
The CYP2C8 inhibitor trimethoprim increases the plasma concentrations of repaglinide in healthy subjects.
Trial report in British journal of clinical pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 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
- Pioglitazone, an in vitro inhibitor of CYP2C8 and CYP3A4, does not increase the plasma concentrations of the CYP2C8 and CYP3A4 substrate repaglinide.European journal of clinical pharmacology · 2006Trial
- The impact of CYP2C8 polymorphism and grapefruit juice on the pharmacokinetics of repaglinide.British journal of clinical pharmacology · 2006Trial
- The effect of trimethoprim on CYP2C8 mediated rosiglitazone metabolism in human liver microsomes and healthy subjects.British journal of clinical pharmacology · 2005Trial
- Lack of effect of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide.British journal of clinical pharmacology · 2004Trial
- Toxicokinetics and analytical toxicology of the phenmetrazine-derived new psychoactive substance 3,4-methylenedioxyphenmetrazine studied by means of in vitro systems.Archives of toxicology · 2025Article
- CYP2C8-Mediated Drug-Drug Interactions and the Factors Influencing the Interaction Magnitude.Drug design, development and therapy · 2025Review
- Hepatic OATP1B zonal distribution: Implications for rifampicin-mediated drug-drug interactions explored within a PBPK framework.CPT: pharmacometrics & systems pharmacology · 2024Article
- Effect of Myricetin on CYP2C8 Inhibition to Assess the Likelihood of Drug Interaction UsingACS omega · 2022Article
- Assessment of Metabolic Interaction between Repaglinide and Quercetin via Mixed Inhibition in the Liver: In Vitro and In Vivo.Pharmaceutics · 2021Article
- A Physiologically-Based Pharmacokinetic Model of Trimethoprim for MATE1, OCT1, OCT2, and CYP2C8 Drug-Drug-Gene Interaction Predictions.Pharmaceutics · 2020Article
- Severe hypoglycemia caused by a small dose of repaglinide and concurrent use of nilotinib and febuxostat in a patient with type 2 diabetes.Diabetology international · 2020Article
- Quantitative Prediction of Interactions Mediated by Transporters and Cytochromes: Application to Organic Anion Transporting Polypeptides, Breast Cancer Resistance Protein and Cytochrome 2C8.Clinical pharmacokinetics · 2020Article
- Article
- Building in-house PBPK modelling tools for oral drug administration from literature information.ADMET & DMPK · 2019Article
- Drug interactions of meglitinide antidiabetics involving CYP enzymes and OATP1B1 transporter.Therapeutic advances in endocrinology and metabolism · 2018Review
- Progress in Prediction and Interpretation of Clinically Relevant Metabolic Drug-Drug Interactions: a Minireview Illustrating Recent Developments and Current Opportunities.Current pharmacology reports · 2017Review
- Basic concepts in physiologically based pharmacokinetic modeling in drug discovery and development.CPT: pharmacometrics & systems pharmacology · 2013Article
- A review of the efficacy and safety of oral antidiabetic drugs.Expert opinion on drug safety · 2013Review
- Importance of multi-p450 inhibition in drug-drug interactions: evaluation of incidence, inhibition magnitude, and prediction from in vitro data.Chemical research in toxicology · 2012Review
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
aimsOur aim was to investigate the effect of the CYP2C8 inhibitor trimethoprim on the pharmacokinetics and pharmacodynamics of the antidiabetic drug repaglinide, and to examine the influence of the former on the metabolism of the latter in vitro.
methodsIn a randomized, double-blind, crossover study with two phases, nine healthy volunteers took 160 mg trimethoprim or placebo orally twice daily for 3 days. On day 3, 1 h after the last dose of trimethoprim or placebo, they ingested a single 0.25 mg dose of repaglinide. Plasma repaglinide and blood glucose concentrations were measured for up to 7 h post-dose. In addition, the effect of trimethoprim on the metabolism of repaglinide by human liver microsomes was investigated.
resultsTrimethoprim raised the AUC(0, infinity ) and C(max) of repaglinide by 61% (range, 30-117%; P= 0.0008) and 41% (P = 0.005), respectively, and prolonged the t((1/2)) of repaglinide from 0.9 to 1.1 h (P = 0.001). Trimethoprim had no significant effect on the pharmacokinetics of its aromatic amine metabolite (M1), but decreased the M1 : repaglinide AUC(0, infinity ) ratio by 38% (P = 0.0005). No effect of trimethoprim on the blood glucose-lowering effect of repaglinide was detectable. In vitro, trimethoprim inhibited the metabolism of (220 nm) repaglinide in a concentration-dependent manner.
conclusionsTrimethoprim raised the plasma concentrations of repaglinide probably by inhibiting its CYP2C8-mediated biotransformation. Although the interaction did not significantly enhance the effect of repaglinide on blood glucose concentration at the drug doses used, the possibility of an increased risk of hypoglycaemia should be considered during concomitant use of trimethoprim and repaglinide in patients with diabetes.
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Registered trials
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.