Pharmacokinetic and pharmacodynamic evaluation of macitentan , a novel endothelin receptor antagonist for the treatment of pulmonary arterial hypertension

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.; This review discusses the pharmacokinetics (PK) and pharmacodynamics (PD) of macitentan and its drug interaction potential based on preclinical and clinical data.; 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.