Biomaterial Database

Clinical pharmacokinetics and pharmacodynamics of the endothelin receptor antagonist macitentan. 2015

P N Sidharta, and A Treiber, and J Dingemanse

Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123, Allschwil, Switzerland, patricia.sidharta@actelion.com.

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 ETA and ETB 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.

UI	MeSH Term	Description	Entries
D011743	Pyrimidines	A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013449	Sulfonamides	A group of compounds that contain the structure SO2NH2.	Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D016032	Randomized Controlled Trials as Topic	Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table.	Clinical Trials, Randomized,Controlled Clinical Trials, Randomized,Trials, Randomized Clinical
D017326	Clinical Trials, Phase III as Topic	Works about comparative studies to verify the effectiveness of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques determined in phase II studies. During these trials, patients are monitored closely by physicians to identify any adverse reactions from long-term use. These studies are performed on groups of patients large enough to identify clinically significant responses and usually last about three years. This concept includes phase III studies conducted in both the U.S. and in other countries.	Clinical Trials, Phase 3 as Topic,Drug Evaluation, FDA Phase 3 as Topic,Drug Evaluation, FDA Phase III as Topic,Evaluation Studies, FDA Phase 3 as Topic,Evaluation Studies, FDA Phase III as Topic
D065128	Endothelin Receptor Antagonists	Compounds and drugs that bind to and inhibit or block the activation of ENDOTHELIN RECECPTORS.	Endothelin Antagonist,Endothelin Receptor Antagonist,Endothelin Antagonists,Antagonist, Endothelin,Antagonist, Endothelin Receptor,Antagonists, Endothelin,Antagonists, Endothelin Receptor,Receptor Antagonist, Endothelin