Macitentan was developed by modifying the structure of the endothelin receptor antagonist bosentan. It stops endothelin from binding to the endothelin A and B receptors. These receptors are associated with vasoconstriction. Although the maximum plasma concentration is reached eight hours after an oral dose, macitentan has a rapid onset of effect. The drug is metabolised, mainly by cytochrome P450 3A4, to form an active metabolite. Macitentan has a half-life of 16 hours and its active metabolite has a half-life of 48 hours. Most of the metabolites are excreted in the urine.