Trial reportBritish journal of clinical pharmacology2013
Effects of clopidogrel and itraconazole on the disposition of efavirenz and its hydroxyl metabolites: exploration of a novel CYP2B6 phenotyping index.
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. An erratum has been issued. Cited by 13 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
13 citing papers in PubMed, 27 citations in OpenAlex.
- Inhibition of Cytochrome P450 2B6 Activity by Voriconazole Profiled Using Efavirenz Disposition in Healthy Volunteers.Antimicrobial agents and chemotherapy · 2016Trial
- Rifampin enhances cytochrome P450 (CYP) 2B6-mediated efavirenz 8-hydroxylation in healthy volunteers.Drug metabolism and pharmacokinetics · 2016Trial
- Population pharmacogenetic-based pharmacokinetic modeling of efavirenz, 7-hydroxy- and 8-hydroxyefavirenz.Journal of clinical pharmacology · 2014Trial
- Drug-Drug Interactions Between HIV Antivirals and Concomitant Drugs in HIV Patients: What We Know and What We Need to Know.Pharmaceutics · 2024Review
- Quantitative Prediction of Drug Interactions Caused by Cytochrome P450 2B6 Inhibition or Induction.Clinical pharmacokinetics · 2022Article
- Sources of Interindividual Variability.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Therapeutic activities of naringenin on efavirenz-induced sleep-like disorder in the midbrain of white albino mice.Iranian journal of basic medical sciences · 2020Article
- Variants in the CYP2B6 3'UTR Alter In Vitro and In Vivo CYP2B6 Activity: Potential Role of MicroRNAs.Clinical pharmacology and therapeutics · 2018Article
- Evaluation of CYP2B6 Induction and Prediction of Clinical Drug-Drug Interactions: Considerations from the IQ Consortium Induction Working Group-An Industry Perspective.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Towards a Best Practice Approach in PBPK Modeling: Case Example of Developing a Unified Efavirenz Model Accounting for Induction of CYPs 3A4 and 2B6.CPT: pharmacometrics & systems pharmacology · 2016Article
- Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy.Therapeutics and clinical risk management · 2015Review
- Pharmacogenomics of anti-platelet and anti-coagulation therapy.Current cardiology reports · 2013Review
- Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance.Frontiers in genetics · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
aimsTo evaluate the effects of clopidogrel and itraconazole on the disposition of efavirenz and its hydroxyl metabolites in relation to the CYP2B6*6 genotype and explore potential phenotyping indices for CYP2B6 activity in vivo using a low dose of oral efavirenz.
methodsWe conducted a randomized three phase crossover study in 17 healthy Korean subjects pre-genotyped for the CYP2B6*6 allele (CYP2B6*1/*1, n = 6; *1/*6, n = 6; *6/*6, n = 5). Subjects were pretreated with clopidogrel (75 mg day(-1) for 4 days), itraconazole (200 mg day(-1) for 6 days), or placebo and then given a single dose of efavirenz (200 mg). The plasma (0-120 h) and urine (0-24 h) concentrations of efavirenz and its metabolites (7- and 8-hydroxyefavirenz and 8,14-dihydroxyefavirenz) were determined by LC/MS/MS.
resultsThis study is the first to delineate quantitatively the full (phase I and II) metabolic profile of efavirenz and its three hydroxyl metabolites in humans. Clopidogrel pretreatment markedly decreased AUC(0,48 h), C(max) and Ae(0,24 h) for 8,14-dihydroxyefavirenz, compared with placebo; 95% CI of the ratios were 0.55, 0.73, 0.30, 0.45 and 0.25, 0.47, respectively. The 8,14-dihydroxyefavirenz : efavirenz AUC(0,120 h) ratio was significantly correlated with the weight-adjusted CL/F of efavirenz (r(2) ≈ 0.4, P < 0.05), differed with CYP2B6*6 genotype and was affected by clopidogrel pretreatment (P < 0.05) but not by itraconazole pretreatment.
conclusionsThe disposition of 8,14-dihydroxy-EFV appears to be sensitive to CYP2B6 activity alterations in human subjects. The 8,14-dihydroxyefaviremz : efavirenz AUC(0,120 h) ratio is attractive as a candidate phenotyping index for CYP2B6 activity in vivo.
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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.