Document Detail


Macitentan, a tissue-targeting endothelin receptor antagonist for the potential oral treatment of pulmonary arterial hypertension and idiopathic pulmonary fibrosis.
MedLine Citation:
PMID:  20730702     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Macitentan (ACT-064992), under development by Actelion Ltd in collaboration with Japanese licensee Nippon Shinyaku Co Ltd, is an orally active, non-peptide dual endothelin (ET)(A) and ET(B) receptor antagonist for the potential treatment of idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Scientific evidence suggests that the ET system may play an important role in the pathobiology of several cardiovascular diseases. A major therapeutic advance for the treatment of patients with PAH and IPF has been the pharmacological control of the activated ET system with ET receptor antagonists. Macitentan, because of its ability to target the tissues and to block both ET(A) and ET(B) receptors, is emerging as a new agent to treat cardiovascular disorders associated with chronic tissue ET system activation. The phase I and II clinical trials conducted to date have demonstrated that macitentan increases plasma levels of ET-1, displays dose-dependent pharmacokinetics, and was well tolerated in healthy volunteers and patients. At the time of publication, a phase II trial in patients with IPF and a phase III trial in patients with PAH was ongoing. It is expected that the results of these trials will validate the safety and efficacy of macitentan.
Authors:
Shahzad G Raja
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Current opinion in investigational drugs (London, England : 2000)     Volume:  11     ISSN:  2040-3429     ISO Abbreviation:  Curr Opin Investig Drugs     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-23     Completed Date:  2011-02-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100965718     Medline TA:  Curr Opin Investig Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  1066-73     Citation Subset:  IM    
Affiliation:
Harefield Hospital, Department of Cardiothoracic Surgery, Royal Brompton & Harefield NHS Trust, Hill End Road, Harefield, London, UB9 6JH, UK. drrajashahzad@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Cardiovascular Diseases / drug therapy
Clinical Trials as Topic
Dogs
Drug Evaluation, Preclinical
Humans
Hypertension, Pulmonary / drug therapy
Idiopathic Pulmonary Fibrosis / drug therapy*
Male
Pyrimidines / administration & dosage,  adverse effects,  pharmacokinetics,  therapeutic use*
Rats
Receptors, Endothelin / antagonists & inhibitors*,  metabolism
Sulfonamides / administration & dosage,  adverse effects,  pharmacokinetics,  therapeutic use*
Chemical
Reg. No./Substance:
0/N-(5-(4-bromophenyl)-6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)pyrimidin-4-yl)-N'-propylaminosulfonamide; 0/Pyrimidines; 0/Receptors, Endothelin; 0/Sulfonamides

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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