<unk>  is taken as a 10 mg oral dose once a day. Its half-life in humans is about 16 hours and steady state is reached by the third day of administration. It is absorbed slowly into the plasma.<unk>  dealkylates into the active metabolite ACT-132577, which reaches its peak plasma concentration about 30 hours after the first dose is administered, and has a half-life of approximately 48 hours. Although ACT-132577 has a lower affinity for the ET receptors than its parent compound, It maintains higher plasma concentrations than<unk> . Both compounds can be excreted from the body through the urine or feces. Co-administration of ciclosporin has only a slight effect on the concentrations of<unk>  and its active metabolite, while rifampicin decreases the area under the curve (AUC) of the drug's blood plasma concentration by 79%, and ketoconazole approximately doubles it. This corresponds to the finding that<unk>  is mainly metabolised via the liver enzyme CYP3A4. ACT-132577, the active metabolite of<unk>  Experimental pharmacokinetics<unk>  has slow association kinetics. Its potency increases 6.3-fold when it is pre-incubated with pulmonary arterial smooth muscle cells for 120 minutes compared to 10 minutes with pulmonary arterial smooth muscle cells.<unk>  also has a high receptor occupancy half-life (approximately 17 minutes) compared to bosentan (approximately 70 seconds) and ambrisentan (approximately 40 seconds). This increased receptor occupancy half-life allows<unk>  to act as a non-competitive antagonist of ET receptors. Bosentan and ambrisentan are both competitive antagonists.
Macitentan
Bosentan
Sitaxentan
Ambrisentan
Darusentan
Sildenafil
Telmisartan
Vericiguat