Trial reportEuropean journal of clinical pharmacology2008
Mutual pharmacokinetic interactions between steady-state bosentan and sildenafil.
Trial report in European journal of clinical pharmacology, 2008. 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 57 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
57 citing papers in PubMed, 5 syntheses or guidelines pooled it, 151 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
- Endothelin receptor antagonists for pulmonary arterial hypertension.The Cochrane database of systematic reviews · 2021Pooled it
- Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Pulmonary Hypertension.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2016Guideline
- Endothelin receptor antagonists for pulmonary arterial hypertension.The Cochrane database of systematic reviews · 2013Pooled it
- Hemodynamics in pulmonary arterial hypertension (PAH): do they explain long-term clinical outcomes with PAH-specific therapy?BMC cardiovascular disorders · 2010Pooled 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
- Clarithromycin substantially increases steady-state bosentan exposure in healthy volunteers.British journal of clinical pharmacology · 2014Trial
- The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects.British journal of clinical pharmacology · 2010Trial
- Development of a population pharmacokinetic model using combined paediatric and adult data for four pulmonary arterial hypertension drugs.British journal of clinical pharmacology · 2026Article
- Prevalence of substances with OATP1B1 inhibitory properties in individual case safety reports of suspected statin-associated myopathy - an analysis of Swiss pharmacovigilance data.European journal of clinical pharmacology · 2026Article
- Prevalence of OATP1B-Mediated Drug-Drug Interactions in an Academic Medical Center.Clinical and translational science · 2025Article
- Pharmacogenomics in the Management of Pulmonary Arterial Hypertension: Current Perspectives.Pharmacogenomics and personalized medicine · 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
- Pulmonary vasodilator strategies in neonates with acute hypoxemic respiratory failure and pulmonary hypertension.Seminars in fetal & neonatal medicine · 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
- 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
- Physiologically-Based Pharmacokinetic Modeling Characterizes the CYP3A-Mediated Drug-Drug Interaction Between Fluconazole and Sildenafil in Infants.Clinical pharmacology and therapeutics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe aim of this study was to systematically investigate the mutual pharmacokinetic interactions in healthy volunteers between sildenafil, a phosphodiesterase-5 inhibitor, and bosentan, a dual endothelin receptor antagonist, both approved for treating pulmonary arterial hypertension (PAH).
methodsA randomised, double-blind, placebo-controlled, parallel-group study with three treatment arms (sildenafil plus placebo, bosentan plus placebo and sildenafil plus bosentan) was conducted in 55 healthy male volunteers (51 completers). Study duration was 18 days per treatment group. Sildenafil was administered three times daily on Days 1-6 and 11-16 (20 mg initially, increased to 80 mg after 3 days), and bosentan (125 mg) was administered twice daily on Days 7-17.
resultsOn Day 16, bosentan decreased the maximum plasma concentration of sildenafil (c)(max)) by 55.4% [90% confidence interval (CI) 40.3-66.6%] and the area under the plasma concentration versus time curve over a dosing interval (AUC(tau)) by 62.6% (90% CI 56.8-67.7%). Sildenafil increased bosentan C(max) by 42.0% (90% CI 15.4-74.8%) and (AUC(tau)) by 49.8% (90% CI 28.7-74.5%). Bosentan and sildenafil in combination were well tolerated, with no serious adverse events reported. All adverse events were of mild or moderate intensity.
conclusionsIn healthy volunteers, there is a mutual pharmacokinetic interaction between bosentan and sildenafil that may influence the dosage of each drug in a combination treatment. The clinical implications of combination therapy with bosentan and sildenafil are as yet unknown, and further trials in patients with PAH are needed.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.