Pharmacokinetics and Tolerability of the Novel Oral Prostacyclin IP Receptor Agonist Selexipag

Am J Cardiovasc Drugs. 2015 Jun;15(3):195-203. doi: 10.1007/s40256-015-0117-4.


Purpose: Targeting the prostacyclin pathway is an effective treatment option for pulmonary arterial hypertension (PAH). Patients with PAH have a deficiency of prostacyclin and prostacyclin synthase. Selexipag is an orally available and selective prostacyclin receptor (IP receptor) agonist. Selexipag is hydrolyzed to its active metabolite ACT-333679, also a selective and potent agonist at the IP receptor.

Methods: In this phase I study the pharmacokinetics (PK) and tolerability of single and multiple ascending doses of selexipag were investigated in a double-blind, placebo-controlled manner in 64 healthy male subjects. An additional group of 12 subjects received an open-label dose of selexipag 400 μg in the fasted condition and after a meal.

Results: Maximum plasma concentrations of selexipag and ACT-333679 were reached within 2.5 and 4 h, respectively, with mean half-lives of 0.7-2.3 and 9.4-14.22 h. In the presence of food, exposure to ACT-333679 was decreased by 27 %. The most frequent adverse event was headache. Selexipag was well tolerated up to a single dose of 400 μg and multiple doses of 600 μg following an up-titration step. No relevant treatment-related effects on vital signs, clinical laboratory, and electrocardiogram (ECG) parameters were detected.

Conclusion: Selexipag exhibits a good tolerability profile and PK properties that warrant further investigation.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / administration & dosage*
  • Acetamides / adverse effects
  • Acetamides / pharmacokinetics
  • Acetates / pharmacokinetics*
  • Administration, Oral
  • Adolescent
  • Adult
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Food-Drug Interactions*
  • Half-Life
  • Humans
  • Male
  • Pyrazines / administration & dosage*
  • Pyrazines / adverse effects
  • Pyrazines / pharmacokinetics*
  • Receptors, Epoprostenol / agonists*
  • Young Adult


  • Acetamides
  • Acetates
  • Antihypertensive Agents
  • Pyrazines
  • Receptors, Epoprostenol
  • selexipag
  • (4-((5,6-diphenylpyrazin-2-yl)(isopropyl)amino)butoxy)acetic acid