Selexipag, sold under the brand name Uptravi, is a medication developed for the treatment of pulmonary arterial hypertension (PAH).
It is a prostacyclin receptor agonist
Bioavailability 49%
Protein binding 99%
Metabolism Activation by carboxylesterases, inactivation by CYP2C8 and others.
Elimination half-life 0.8–2.5 h (selexipag) and its active metabolite
6.2–13.5 h (ACT-333679)
Excretion 93% feces
Selexipag and its active metabolite, ACT-333679, the free carboxylic acid, are agonists of the prostacyclin receptor, which leads to vasodilation in the pulmonary circulation.
Taken by mouth or administered intravenously.
The most common side effects include headache, diarrhea, nausea and vomiting, jaw pain, myalgia, pain in the limbs, arthralgia and flushing.
It is available as a generic medication.
The use of selexipag together with strong inhibitors of the liver enzyme CYP2C8, such as gemfibrozil, is contraindicated because it increases concentrations of selexipag twofold, and its active metabolite 11-fold, potentially leading to more adverse effects.
The adverse effects of selexipag are similar to those of intravenous prostacyclins used for pulmonary arterial hypertension: headache and jaw pain.
An increased risk for hyperthyroidism has also been noted.
ACT-333679 is the active metabolite
Selexipag and its active metabolite ACT-333679 act on the prostacyclin receptor of lung tissue, with the latter being 37-fold more potent.
They are selective for the prostacyclin receptor.
Binding to the prostacyclin receptor leads to three major effects:
increased vasodilation of the arteries, decreased cell proliferation and inhibition of platelet aggregation, all beneficial in the treatment of pulmonary arterial hypertension.
Selexipag is quickly absorbed from the gut and hydrolyzed in the intestines and the liver to ACT-333679 by carboxylesterases.
Bioavailability is about 49%, most likely because of a high first-pass effect. Highest concentrations in the blood plasma are reached after one to three hours for selexipag and after three to four hours for the active metabolite.
About 99% of both substances are bound to plasma proteins, namely to albumin and alpha-1-acid glycoprotein to equal amounts.
The terminal half-life of selexipag is 0.8 to 2.5 hours, that of the active metabolite is 6.2 to 13.5 hours.
FDA granted selexipag orphan drug designation for pulmonary arterial hypertension[11] and for the treatment of chronic thromboembolic pulmonary hypertension.