ArticleBritish journal of clinical pharmacology2005
Bosentan decreases the plasma concentration of sildenafil when coprescribed in pulmonary hypertension.
Article in British journal of clinical pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02484807 (Effect of Pharmacologic Interaction Between Endothelin-Receptor-Antagonists and Phosphodiesterase-5 Inhibitors on Medication Serum Levels and Clinical Disease Status in Patients Wih Pulmonary Arterial Hypertension), which is not on this map. Cited by 55 papers, 2 of them syntheses 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.
Effect of Pharmacologic Interaction Between Endothelin-Receptor-Antagonists and Phosphodiesterase-5 Inhibitors on Medication Serum Levels and Clinical Disease Status in Patients Wih Pulmonary Arterial Hypertension
Who cites it
55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 223 citations in OpenAlex.
- Phosphodiesterase type 5 inhibitor plus endothelin receptor antagonist compared to either alone for group 1 pulmonary arterial hypertension.The Cochrane database of systematic reviews · 2025Pooled it
- Pulmonary arterial hypertension in the elderly: Clinical perspectives.Cardiology journal · 2020Pooled it
- Sildenafil dosed concomitantly with bosentan for adult pulmonary arterial hypertension in a randomized controlled trial.BMC cardiovascular disorders · 2017Trial
- Pharmacokinetic and Pharmacodynamic Comparison of Sildenafil-Bosentan and Sildenafil-Ambrisentan Combination Therapies for Pulmonary Hypertension.Clinical and translational science · 2016Trial
- Pharmacokinetic interactions among imatinib, bosentan and sildenafil, and their clinical implications in severe pulmonary arterial hypertension.British journal of clinical pharmacology · 2015Trial
- Investigation of mutual pharmacokinetic interactions between macitentan, a novel endothelin receptor antagonist, and sildenafil in healthy subjects.British journal of clinical pharmacology · 2014Trial
- The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects.British journal of clinical pharmacology · 2010Trial
- Mutual pharmacokinetic interactions between steady-state bosentan and sildenafil.European journal of clinical pharmacology · 2008Trial
- Development of a population pharmacokinetic model using combined paediatric and adult data for four pulmonary arterial hypertension drugs.British journal of clinical pharmacology · 2026Article
- Population Pharmacokinetics of Sildenafil in Dogs With Naturally Occurring Pulmonary Hypertension.Journal of veterinary pharmacology and therapeutics · 2026Article
- Recent developments in connective tissue disease associated pulmonary arterial hypertension.International journal of cardiology. Congenital heart disease · 2024Review
- State-of-the-art evidence in the treatment of systemic sclerosis.Nature reviews. Rheumatology · 2023Review
- Drug Interactions Associated With Therapies for Pulmonary Arterial Hypertension.The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians · 2022Review
- Safety and tolerability of combination therapy with ambrisentan and tadalafil for the treatment of pulmonary arterial hypertension in children: Real-world experience.Pediatric pulmonology · 2022Observational
- Novel use of riociguat in infants with severe pulmonary arterial hypertension unable to wean from inhaled nitric oxide.Frontiers in pediatrics · 2022Article
- Sildenafil 4.0-Integrated Synthetic Chemistry, Formulation and Analytical Strategies Effecting Immense Therapeutic and Societal Impact in the Fourth Industrial Era.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Safety and efficacy of the endothelin receptor antagonist macitentan in pediatric pulmonary hypertension.Cardiovascular diagnosis and therapy · 2020Article
- Prostate Cancer Cell Phenotypes Remain Stable Following PDE5 Inhibition in the Clinically Relevant Range.Translational oncology · 2020Article
- Combination therapy with bosentan and sildenafil for refractory digital ulcers and Raynaud's phenomenon in a 30-year-old woman with systemic sclerosis: Case report and literature review.Journal of scleroderma and related disorders · 2020Article
- Database of adverse events associated with drugs and drug combinations.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo determine whether bosentan decreases the plasma concentration of sildenafil in patients with pulmonary arterial hypertension.
methodsTen patients (aged 39-77 years) with pulmonary arterial hypertension in WHO functional class III received bosentan 62.5 mg twice daily for 1 month, then 125 mg twice daily for a second month. Sildenafil 100 mg was given as a single dose before starting bosentan (visit 1) and at the end of each month of bosentan treatment (visits 2 and 3). Sildenafil and its primary metabolite, desmethylsildenafil, were measured in plasma at 0 h and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 and 24 h using liquid chromatography-tandem mass spectrometry. Statistical analysis was by repeated measures anova, using log transformed data where appropriate.
resultsTreatment with bosentan 62.5 mg twice daily for 4 weeks was associated with a two-fold increase in sildenafil clearance/F and a 50% decrease in the AUC (P < 0.001). Increasing the dose of bosentan to 125 mg twice daily led to a further increase in sildenafil oral clearance and decrease in the AUC (P < 0.001 vs. 62.5 mg bosentan). The ratio of AUC on bosentan treatment relative to that of visit 1 was 0.47 [95% confidence interval (CI) 0.36, 0.61] for visit 2 and 0.31 (95% CI 0.23, 0.41) for visit 3 (P < 0.001). Sildenafil C(max) fell from 759 ng ml(-1) on visit 1 to 333 ng ml(-1) on visit 3 (P < 0.01) and there was a significant decrease in the plasma half-life of sildenafil on the higher bosentan dose (P < 0.05). The AUC and plasma half-life of desmethylsildenafil was also decreased by bosentan in a dose-dependent manner (P < 0.01).
conclusionsBosentan significantly decreases the plasma concentration of sildenafil when coadministered to patients with pulmonary hypertension.
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