Trial reportEuropean journal of clinical pharmacology2013
Interaction of ambrisentan with clarithromycin and its modulation by polymorphic SLCO1B1.
Trial report in European 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 12 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
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 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
- Dose-Dependent Bioavailability and CYP3A Inhibition Contribute to Non-Linear Pharmacokinetics of Voriconazole.Clinical pharmacokinetics · 2016Trial
- Understanding Coproporphyrins and Their Disposition: Coproporphyrinuria is Common, of Diverse Cause, and Rarely Indicates Porphyria.The American journal of medicine · 2025Review
- Physiologically-based pharmacokinetic modeling to predict CYP3A4-mediated drug-drug interactions of finerenone.CPT: pharmacometrics & systems pharmacology · 2022Article
- Evaluation of herb-drug interaction of ambrisentan with shikonin based on UPLC-MS/MS.Pharmaceutical biology · 2021Article
- Ambrisentan use in a HIV-1 infected patient with end-stage renal disease and pulmonary hypertension: minimal removal by hemodialysis - a case report.BMC nephrology · 2020Article
- Identification and Evaluation of Clinical Substrates of Organic Anion Transporting Polypeptides 1B1 and 1B3.Clinical and translational science · 2019Article
- PBPK Models for CYP3A4 and P-gp DDI Prediction: A Modeling Network of Rifampicin, Itraconazole, Clarithromycin, Midazolam, Alfentanil, and Digoxin.CPT: pharmacometrics & systems pharmacology · 2018Article
- Autoinhibitory properties of the parent but not of the N-oxide metabolite contribute to infusion rate-dependent voriconazole pharmacokinetics.British journal of clinical pharmacology · 2017Article
- Clarithromycin, Midazolam, and Digoxin: Application of PBPK Modeling to Gain New Insights into Drug-Drug Interactions and Co-medication Regimens.The AAPS journal · 2017Article
- Ritonavir is the best alternative to ketoconazole as an index inhibitor of cytochrome P450-3A in drug-drug interaction studies.British journal of clinical pharmacology · 2015Review
- Nonalcoholic steatohepatitis in precision medicine: Unraveling the factors that contribute to individual variability.Pharmacology & therapeutics · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe assessed the effect of cytochrome P450 (CYP) 3A4 and the OATP1B1 inhibitor clarithromycin on ambrisentan steady-state kinetics and its relationship to the SLCO1B1 15 haplotype in healthy volunteers.
methodsIn this open-label, monocenter, one-sequence crossover clinical trial ten male healthy participants were stratified according to CYP2C19 and SLCO1B1 (encoding for OATP1B1) genotype into two groups: group 1 (n = 6), with CYP2C19 1/1 (extensive metabolizer, EM) and SLCO1B1 wild-type; group 2 (n = 4), with CYP2C19 EM and homozygous (n = 3) or heterozygous for SLCO1B1 15 (n = 1). The participants were administered a once-daily oral dose of 5 mg ambrisentan on study days 1 and days 3-14 and twice-daily oral doses of 500 mg clarithromycin on study days 11-14. To monitor CYP3A activity 3 mg midazolam was given orally 1 day before the first ambrisentan administration and on days 1, 10, and 14 of ambrisentan treatment. Ambrisentan plasma kinetics was assessed on days 1 (single dose), 10 (steady-state), and 14 (CYP3A4/OATP1B1 inhibition by clarithromycin).
resultsConsistent with the expectation that ambrisentan does not induce its own metabolism, ambrisentan exposure and peak concentration (Cmax) were similar after the first dose and at steady-state. Clarithromycin increased the area under the plasma concentration-time curve of ambrisentan by 41 % and Cmax by 27 % (n = 10, both p < 0.05). No contribution of SLCO1B1*15 to the extent of this interaction was observed.
conclusionsClarithromycin increased ambrisentan exposure to a similar extent to ketoconazole, namely, clinically minor and likely irrelevant.
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