Trial reportBritish journal of clinical pharmacology2014
Investigation of mutual pharmacokinetic interactions between macitentan, a novel endothelin receptor antagonist, and sildenafil in healthy subjects.
Trial report in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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.
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, 26 citations in OpenAlex.
- Effect of Once-Daily Macitentan 75 mg on the Pharmacokinetics of Sildenafil, Riociguat, or Rosuvastatin in Healthy Male Participants.Journal of clinical pharmacology · 2026Article
- 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
- The endothelin receptor antagonist macitentan for the treatment of pulmonary arterial hypertension: A cross-species comparison of its cytochrome P450 induction pattern.Pharmacology research & perspectives · 2020Article
- Safety and tolerability of macitentan in the management of pulmonary arterial hypertension: an update.Drug, healthcare and patient safety · 2019Article
- Endothelin-receptor antagonists in the management of pulmonary arterial hypertension: where do we stand?Vascular health and risk management · 2018Review
- Sildenafil in Infants and Children.Children (Basel, Switzerland) · 2017Review
- Physiologically-Based Pharmacokinetic Modeling of Macitentan: Prediction of Drug-Drug Interactions.Clinical pharmacokinetics · 2016Article
- Clinical pharmacokinetics and pharmacodynamics of the endothelin receptor antagonist macitentan.Clinical pharmacokinetics · 2015Review
- Macitentan for the treatment of pulmonary arterial hypertension.Vascular health and risk management · 2014Review
- Safety and efficacy of transitioning from the combination of bosentan and sildenafil to alternative therapy in patients with pulmonary arterial hypertension.Pulmonary circulationArticle
- Liver injury due to endothelin receptor antagonists: a real-world study based on post-marketing drug monitoring data.Therapeutic advances in respiratory diseaseArticle
- Treatment of pulmonary arterial hypertension with the dual endothelin receptor antagonist macitentan: clinical evidence and experience.Therapeutic advances in respiratory diseaseReview
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
aimTo study the mutual pharmacokinetic interactions between macitentan, an endothelin receptor antagonist, and sildenafil in healthy male subjects.
methodsIn this open-label, randomized, three way crossover study, 12 healthy male subjects received the following oral treatments: A) a loading dose of 30 mg macitentan on day 1 followed by 10 mg once daily for 3 days, B) sildenafil 20 mg three times a day for 3 days and a single 20 mg dose on day 4 and C) both treatments A and B concomitantly. Plasma concentration-time profiles of macitentan and its active metabolite ACT-132577 (treatments A and C) and sildenafil and its N-desmethyl metabolite (treatments B and C) were determined on day 4 and analyzed non-compartmentally.
resultsThe pharmacokinetics of macitentan were not affected by sildenafil. In the presence of sildenafil Cmax and AUCτ of the metabolite ACT-132577 decreased with geometric mean ratios (90% confidence interval (CI)) of 0.82 (0.76, 0.89) and 0.85 (90% CI 0.80, 0.91), respectively. In the presence of macitentan, plasma concentrations of sildenafil were higher than during treatment with sildenafil alone, resulting in increased Cmax and AUCτ values. The respective geometric mean ratios were 1.26 (90% CI 1.07, 1.48) and 1.15 (90% CI 0.94, 1.41). The pharmacokinetics of N-desmethylsildenafil were not affected by macitentan. All treatments were well tolerated.
conclusionA minor, not clinically relevant, pharmacokinetic interaction was observed between macitentan and sildenafil. Based on these results, no dose adjustment of either compound appears necessary during concomitant treatment with macitentan and sildenafil.
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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.