title: Pharmacokinetic and pharmacodynamic evaluation of macitentan , a novel endothelin receptor antagonist for the treatment of pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a chronic disorder of the pulmonary vasculature characterized by elevated mean pulmonary arterial pressure eventually leading to right-sided heart failure and premature death. Macitentan is an oral, once-daily, dual endothelin (ET)A and ETB receptor antagonist with high affinity and sustained receptor binding that was approved in the USA, Europe, Canada, and Switzerland for the treatment of PAH.
  
  
  METHODS
  This review discusses the pharmacokinetics (PK) and pharmacodynamics (PD) of macitentan and its drug interaction potential based on preclinical and clinical data.
  
  
  CONCLUSIONS
  Up to date, macitentan is the only registered treatment for PAH that significantly reduced morbidity and mortality as a combined endpoint in a long-term event-driven study. The safety profile of macitentan is favorable with respect to hepatic safety and edema/fluid retention and may be better than that of other ET receptor antagonists such as bosentan and ambrisentan. The PK profile supports a once-a-day dosing regimen. Macitentan has limited interactions with other drugs. Based on these characteristics macitentan is an important new addition to the treatment of PAH.
authors.affiliation: Actelion Pharmaceuticals Ltd., Department of Clinical Pharmacology , Gewerbestrasse 16, CH-4123 Allschwil , Switzerland +41 61 656686 ; +41 61 5656200 ; patricia.sidharta@actelion.com.
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Sidharta
authors.forename: Stephan
authors.initials: S
authors.lastname: Krähenbühl
authors.forename: Jasper
authors.initials: J
authors.lastname: Dingemanse
mesh_terms: D000818:Animals; D000077300:Bosentan; D004347:Drug Interactions; D065130:Endothelin A Receptor Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D065131:Endothelin B Receptor Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D010666:Phenylpropionates / Q000627:therapeutic use; D011724:Pyridazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D010666:Phenylpropionates; D011724:Pyridazines; D011743:Pyrimidines; D013449:Sulfonamides; C467894:ambrisentan; D000077300:Bosentan; C533860:macitentan
keywords: endothelin receptor antagonist; macitentan pulmonary arterial hypertension; pharmacodynamics; pharmacokinetics