Trial reportEuropean journal of clinical pharmacology2011
Macitentan: entry-into-humans study with a new endothelin receptor antagonist.
Trial report in European journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- 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
- Bioequivalence and the food effect of macitentan/tadalafil 10/20 fixed-dose combination tablets versus the use of single-component tablets in healthy subjects.Pharmacology research & perspectives · 2024Trial
- Investigation of mutual pharmacokinetic interactions between macitentan, a novel endothelin receptor antagonist, and sildenafil in healthy subjects.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
- Investigation of the Effects of Switching from Bosentan to Macitentan in Pediatric Pulmonary Hypertension Patients.Sisli Etfal Hastanesi tip bulteni · 2026Article
- Structure-Property Relationships Reported for the New Drugs Approved in 2024.Mini reviews in medicinal chemistry · 2025Review
- Current and future strategies for targeting the endothelin pathway in cardiovascular disease.Nature cardiovascular research · 2023Review
- The EDN1/EDNRA/β‑arrestin axis promotes colorectal cancer progression by regulating STAT3 phosphorylation.International journal of oncology · 2023Article
- The endothelin receptor antagonist macitentan ameliorates endothelin-mediated vasoconstriction and promotes the survival of retinal ganglion cells in rats.Frontiers in ophthalmology · 2023Article
- A Population Pharmacokinetic Model of Macitentan and Its Active Metabolite Aprocitentan in Healthy Volunteers and Patients with Pulmonary Arterial Hypertension.Clinical pharmacokinetics · 2021Article
- Tritylamine as an Ammonia Surrogate in the Ugi Reaction Provides Access to Unprecedented 5-Sulfamido Oxazoles Using Burgess-type Reagents.Organic letters · 2021Article
- Bioequivalence of macitentan and tadalafil given as fixed-dose combination or single-component tablets in healthy subjects.British journal of clinical pharmacology · 2020Article
- Safety and efficacy of the endothelin receptor antagonist macitentan in pediatric pulmonary hypertension.Cardiovascular diagnosis and therapy · 2020Article
- 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
- Update on Endothelin Receptor Antagonists in Hypertension.Current hypertension reports · 2018Review
- Activation mechanism of endothelin ETNature · 2016Article
- The heart as an extravascular target of endothelin-1 in particulate matter-induced cardiac dysfunction.Pharmacology & therapeutics · 2016Review
- Endothelin.Pharmacological reviews · 2016Review
- Sandwich-Cultured Hepatocytes as a Tool to Study Drug Disposition and Drug-Induced Liver Injury.Journal of pharmaceutical sciences · 2016Review
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
purposeTo study the pharmacokinetics, pharmacodynamics, and tolerability of rising single doses of macitentan, an endothelin receptor antagonist, in healthy male subjects.
methodsThis double-blind, placebo-controlled study was performed in seven groups of eight healthy male subjects. Doses of 0.2, 1, 5, 25, 100, 300 and 600 mg or placebo (two subjects per group) were administered. Plasma macitentan and endothelin-1 and serum total bile salt concentrations were measured and analysed non-compartmentally. Plasma and urine were analysed qualitatively for the presence of metabolites and one of these, ACT-132577, was also measured quantitatively in plasma. Standard tolerability measurements were performed throughout the study.
resultsMacitentan was slowly absorbed and, at a dose of 300 mg, the t(1/2) (95% confidence interval, CI) was 17.5 h (14.1, 21.8). The dose-proportionality coefficient β for C(max) (95% CI) was 0.83 (0.79, 0.87) indicating less than dose-proportional pharmacokinetics of macitentan. In plasma, a pharmacologically active oxidative depropyl metabolite, ACT-132577, was found whereas in urine two minor metabolites were detected. The t(1/2) of ACT-132577 (95% CI) was 65.6 h (53.1, 80.9). Macitentan dose-dependently increased endothelin-1 concentrations up to 2.2-fold (95% CI 1.4, 2.4) at a dose of 600 mg, but had no consistent effect on total bile salts. Macitentan was well tolerated up to and including a dose of 300 mg, the maximum tolerated dose. Headache, nausea and vomiting were dose-limiting adverse events.
conclusionThe pharmacokinetic and tolerability profile of macitentan is consistent with a once-a-day dosing regimen and warrants further investigation in clinical studies.
Indexed as
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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.