title: Pharmacokinetic drug evaluation of selexipag for the treatment of pulmonary arterial hypertension.
abstract: Management of pulmonary arterial hypertension (PAH) remains challenging even in the contemporary era. Intravenous prostacyclin therapy, while associated with decreased mortality, has practical limitations and requires significant lifestyle modifications. The recently approved long-acting oral IP prostacyclin receptor agonist for treatment of PAH, selexipag, is a non-prostanoid agent that vasodilates, impacts remodeling (anti-proliferative), reduces endothelial cell dysfunction, inhibits platelet aggregation (anti-thrombotic), and increases right heart inotropy. Areas covered: This review discusses the limitations of non-oral prostacyclin therapy for PAH and describes the factors which led to successful development of selexipag in in vitro and preclinical studies. We review the pharmacokinetics and pharmacodynamics of selexipag. We further discuss the methodology and results of phase II and III trials, which led to approval of selexipag for PAH management. Expert opinion: As compared to previously developed oral prostacyclins, selexipag has limited adverse effects despite similar or better efficacy. Its final place in the treatment paradigm is not yet clear but it does represent a significant advance in the area of oral PAH therapy.
authors.affiliation: a Department of Medicine , University of Massachusetts Medical School , Worcester , MA , USA.
authors.forename: Mayank
authors.initials: M
authors.lastname: Sardana
authors.affiliation: b Department of Medicine , Boston University School of Medicine , Boston , MA , USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Moll
authors.affiliation: c Pulmonary Center , Boston University School of Medicine , Boston , MA , USA.
authors.forename: Harrison W
authors.initials: HW
authors.lastname: Farber
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000401:mortality; D011719:Pyrazines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D011719:Pyrazines; C523468:selexipag
keywords: Pulmonary arterial hypertension; prostacyclin; selexipag