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| Clinical data | |
|---|---|
| Trade names | Uptravi |
| Other names | ACT-293987, NS-304 |
| License data | |
| Routes of administration | By mouth,intravenous |
| Drug class | prostacyclin receptor agonist |
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| Pharmacokinetic data | |
| Bioavailability | 49% |
| Protein binding | 99% |
| Metabolism | Activation bycarboxylesterases, inactivation byCYP2C8 and others |
| Metabolites | ACT-333679, the free acid (active metabolite) |
| Eliminationhalf-life | 0.8–2.5 h (selexipag) and 6.2–13.5 h (ACT-333679) |
| Excretion | 93% faeces |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.237.916 |
| Chemical and physical data | |
| Formula | C26H32N4O4S |
| Molar mass | 496.63 g·mol−1 |
| 3D model (JSmol) | |
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Selexipag, sold under the brand nameUptravi, is a medication developed byActelion for the treatment ofpulmonary arterial hypertension (PAH).[3][4] Selexipag and itsactive metabolite,ACT-333679 (or MRE-269, the freecarboxylic acid), areagonists of theprostacyclin receptor, which leads tovasodilation in the pulmonary circulation.[5] It is takenby mouth or administered intravenously.[3][6]
The most common side effects include headache, diarrhea, nausea and vomiting, jaw pain, myalgia (muscle pain), pain in the limbs, arthralgia (joint pain) and flushing.[4]
It is available as ageneric medication.[7]
Selexipag isindicated for the treatment of pulmonary arterial hypertension.[3][4]
In the European Union, use of selexipag together with strong inhibitors of the liver enzymeCYP2C8, such asgemfibrozil, is contraindicated because it increases concentrations of selexipag twofold, and its active metabolite 11-fold, potentially leading to more adverse effects.[4][8]
The adverse effects of selexipag are similar to those of intravenousprostacyclins used for pulmonary arterial hypertension. Common side effects include headache and jaw pain. An increased risk forhyperthyroidism has also been noted in people taking selexipag.[9]
Selexipag and itsactive 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 this receptor leads to three major effects: increasedvasodilation of the arteries, decreasedcell proliferation and inhibition ofplatelet aggregation,[9] all beneficial in the treatment of pulmonary arterial hypertension.
Selexipag is quickly absorbed from the gut andhydrolyzed in the intestines and the liver to ACT-333679 bycarboxylesterases. Absolutebioavailability is about 49%, most likely because of a highfirst-pass effect. Highest concentrations in theblood plasma are reached after one to three hours for selexipag and after three to four hours for the active metabolite. When in the circulation, about 99% of both substances are bound toplasma proteins, namely toalbumin andalpha-1-acid glycoprotein to equal amounts.[9]
The liver enzymesCYP2C8 and, to a lesser extent,CYP3A4,hydroxylate anddealkylate the active substance, thereby inactivating it. Besides, ACT-333679 isglucuronidized by the enzymesUGT1A3 andUGT2B7. Theterminal half-life of selexipag is 0.8 to 2.5 hours, that of the active metabolite is 6.2 to 13.5 hours.[9]
The synthesis of celexipag begins from two inexpensive compounds,glycine hydrochloride andbenzil, condensed under basic conditions.[10][11]
The U.S.Food and Drug Administration (FDA) granted selexipagorphan drug designation for pulmonary arterial hypertension[12] and for the treatment of chronic thromboembolic pulmonary hypertension.[13] It was approved by the FDA in December 2015.[3][14]
In the European Union, the drug was approved in May 2016.[4][9]
The expected price for the drug in the US is $160,000 to $170,000 per patient beforerebates.[15]
