Trial reportBritish journal of clinical pharmacology2002
Single- and multiple-dose pharmacokinetics of bosentan and its interaction with ketoconazole.
Trial report in British journal of clinical pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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, 87 citations in OpenAlex.
- Clarithromycin substantially increases steady-state bosentan exposure in healthy volunteers.British journal of clinical pharmacology · 2014Trial
- Investigation of the effects of ketoconazole on the pharmacokinetics of macitentan, a novel dual endothelin receptor antagonist, in healthy subjects.Clinical pharmacokinetics · 2013Trial
- Sensitive voltammetric detection of bosentan using gold nanoparticles-decorated pencil graphite electrode in pharmaceutical formulations and plasma samples.Scientific reports · 2026Article
- Selection of Endothelin Receptor Antagonists in the Treatment of Pulmonary Arterial Hypertension: A Comprehensive Narrative Review.Advances in therapy · 2026Review
- Predicting Systemic and Liver Bosentan Exposure Using Physiologically-Based Pharmacokinetic Modeling.CPT: pharmacometrics & systems pharmacology · 2025Article
- Current and future strategies for targeting the endothelin pathway in cardiovascular disease.Nature cardiovascular research · 2023Review
- Pharmacogenomics in the Management of Pulmonary Arterial Hypertension: Current Perspectives.Pharmacogenomics and personalized medicine · 2023Review
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Candidate Proficiency Test Chemicals to Address Industrial Chemical Applicability Domains forFrontiers in toxicology · 2022Review
- Validation of in vitro methods for human cytochrome P450 enzyme induction: Outcome of a multi-laboratory study.Toxicology in vitro : an international journal published in association with BIBRA · 2019Article
- A simple model to solve a complex drug toxicity problem.Toxicology research · 2019Article
- Manipulating fenestrations in young and old liver sinusoidal endothelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Association of CYP2C9*2 with bosentan-induced liver injury.Clinical pharmacology and therapeutics · 2013Article
- Pharmacologic treatments for pulmonary hypertension: exploring pharmacogenomics.Future cardiology · 2013Review
- Bosentan: a review of its use in the management of digital ulcers associated with systemic sclerosis.Drugs · 2009Review
- Optimizing endothelin receptor antagonist use in the management of pulmonary arterial hypertension.Vascular health and risk management · 2008Review
- Evaluation of human liver slices and reporter gene assays as systems for predicting the cytochrome p450 induction potential of drugs in vivo in humans.Pharmaceutical research · 2006Article
- Clinical pharmacology of bosentan, a dual endothelin receptor antagonist.Clinical pharmacokinetics · 2004Review
- Simple Determination of Bosentan in Plasma Samples by Reversed-Phase High-Performance Liquid Chromatography.Avicenna journal of medical biotechnologyArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe present study was conducted to characterize the single- and multiple-dose pharmacokinetics of bosentan, a dual endothelin receptor antagonist, and to investigate a possible pharmacokinetic interaction with ketoconazole.
methodsIn a randomized, two-way crossover study, 10 healthy male subjects received treatments A and B. Treatment A consisted of a single dose of 62.5 mg bosentan on day 1 followed by 62.5 mg twice daily for 5.5 days. Treatment B consisted of bosentan (62.5 mg twice daily) for 5.5 days plus concomitant ketoconazole (200 mg once daily) for 6 days. Plasma concentrations of bosentan and its three metabolites were measured on days 1 and 7 of treatment A and on day 6 of treatment B.
resultsBosentan was absorbed and eliminated with a tmax of 4.5 h (range 3.5-6.0 h) and a t(1/2) of 5.4 h (95% CI; 4.5, 6.6). Upon multiple dosing, the exposure to bosentan was reduced by 33% without change in tmax and t(1/2). Concomitant administration of ketoconazole increased the Cmax and AUC of bosentan 2.1- (95% CI; 1.5, 2.7) and 2.3-fold (95% CI; 1.8, 2.9), respectively. Exposure to the metabolites was low and represented less than 25% of that to bosentan both after single and multiple doses. In the presence of ketoconazole, formation of the metabolites was inhibited. DISCUSSION: The multiple-dose pharmacokinetics of bosentan are consistent with the phenomenon of auto-induction. In the presence of CYP3A4 inhibitors, bosentan concentrations may be increased 2-fold.
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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.