Trial reportClinical pharmacokinetics2003
Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin.
Trial report in Clinical pharmacokinetics, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 51 citations in OpenAlex.
- Clarithromycin substantially increases steady-state bosentan exposure in healthy volunteers.British journal of clinical pharmacology · 2014Trial
- Almorexant effects on CYP3A4 activity studied by its simultaneous and time-separated administration with simvastatin and atorvastatin.European journal of clinical pharmacology · 2013Trial
- Pharmacokinetic interactions of almorexant with midazolam and simvastatin, two CYP3A4 model substrates, in healthy male subjects.European journal of clinical pharmacology · 2013Trial
- Simvastatin as a treatment for pulmonary hypertension trial.American journal of respiratory and critical care medicine · 2010 · on this mapTrial
- Drug Interactions Associated With Therapies for Pulmonary Arterial Hypertension.The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians · 2022Review
- Impact of Disease and Treatment Response in Drug-Drug Interaction Studies: Osimertinib and Simvastatin in Advanced Non-Small Cell Lung Cancer.Clinical and translational science · 2020Article
- Clinical Pharmacokinetic and Pharmacodynamic Profile of Riociguat.Clinical pharmacokinetics · 2018Review
- Population pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship of riociguat in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.Pulmonary circulation · 2016Article
- Pharmacologic treatments for pulmonary hypertension: exploring pharmacogenomics.Future cardiology · 2013Review
- Successful strategy to improve the specificity of electronic statin-drug interaction alerts.European journal of clinical pharmacology · 2009Article
- Bosentan: a review of its use in the management of digital ulcers associated with systemic sclerosis.Drugs · 2009Review
- General framework for the prediction of oral drug interactions caused by CYP3A4 induction from in vivo information.Clinical pharmacokinetics · 2008Article
- Clinical pharmacology of bosentan, a dual endothelin receptor antagonist.Clinical pharmacokinetics · 2004Review
- An atypical presentation of liver enzyme elevation resulting from bosentan use.Canadian respiratory journalArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn vitro, bosentan has been shown to be a mild inducer of cytochrome P450 (CYP) 2C9 and 3A4. PURPOSE: To investigate in vivo the mutual pharmacokinetic interactions between bosentan and simvastatin, a CYP3A4 substrate.
methodsNine healthy male subjects were treated in a three-period randomised crossover study with: (A) bosentan 125 mg twice daily for 5.5 days; (B) simvastatin 40 mg once daily for 6 days; and (C) bosentan 125 mg twice daily and simvastatin 40 mg once daily for 5.5 and 6 days, respectively. Plasma concentration-time profiles of bosentan and its metabolites (treatments A and C) and simvastatin and beta-hydroxyacid simvastatin (treatments B and C) were determined on day 6.
resultsSteady-state conditions for bosentan and its metabolites were attained on day 4 of treatment. The pharmacokinetic parameters of bosentan and its metabolites were not influenced by concomitant treatment with simvastatin: areas under the plasma concentration-time curve over one administration interval of 12 hours (AUC(tau)) [geometric mean and 95% CI] were 4586 (3719-5656) and 4928 (3945-6156) micro g * h/L. In contrast, bosentan significantly reduced exposure to simvastatin and beta-hydroxyacid simvastatin by 34 and 46%, respectively. AUC(tau) values for simvastatin were 30.5 (23.1-40.2) and 20.0 (15.9-25.1) micro g * h/L and for beta-hydroxyacid simvastatin 43.0 (32.1-57.8) and 23.4 (16.7-32.6) micro g * h/L in treatments B and C, respectively.
conclusionsConcomitant treatment with bosentan reduces the exposure to simvastatin and beta-hydroxyacid simvastatin by approximately 40%, indicating that in vivo bosentan is also a mild inducer of CYP3A4.
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Registered trials
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