Clinical Pharmacokinetics and Pharmacodynamics of the Endothelin Receptor Antagonist Macitentan

• Published in: Clinical pharmacokinetics Vol. 54; no. 5; pp. 457 - 471
• Main Authors: Sidharta, P. N., Treiber, A., Dingemanse, J.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.05.2015; Springer Nature B.V
• Subjects: Clinical Trials, Phase III as Topic; Endothelin Receptor Antagonists - pharmacokinetics; Endothelin Receptor Antagonists - pharmacology; Humans; Internal Medicine; Medicine; Medicine & Public Health; Pharmacology/Toxicology; Pharmacotherapy; Pyrimidines - pharmacokinetics; Pyrimidines - pharmacology; Randomized Controlled Trials as Topic; Review; Review Article; Sulfonamides - pharmacokinetics; Sulfonamides - pharmacology; Bosentan; Healthy Male Subject; Hepatic Impairment; Pulmonary Arterial Hypertension; Breast Cancer Resistance Protein
• ISSN: 0312-5963; 1179-1926; 1179-1926
• DOI: 10.1007/s40262-015-0255-5

Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vascular system, which leads to right-sided heart failure and ultimately death if untreated. Treatments to regulate the pulmonary vascular pressure target the prostacyclin, nitric oxide, and endothelin (ET) pathways. Macitentan, an oral, once-daily, dual ET A and ET B receptor antagonist with high affinity and sustained receptor binding is the first ET receptor antagonist to show significant reduction of the risk of morbidity and mortality in PAH patients in a large-scale phase III study with a long-term outcome. Here we present a review of the available clinical pharmacokinetic, pharmacodynamic, pharmacokinetic/pharmacodynamic relationship, and drug–drug interaction data of macitentan in healthy subjects, patients with PAH, and in special populations.