Clopidogrel, a CYP2C8 inhibitor, causes a clinically relevant increase in the systemic exposure to the active metabolite of selexipag in healthy subjects.

ABSTRACT:

Aims

Selexipag is a prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension. Cytochrome P450 (CYP) 2C8 is involved in the metabolism of selexipag and its active metabolite, ACT-333679. This study evaluated the interaction of selexipag and clopidogrel, a CYP2C8 inhibitor.

Methods

The study had a 2-treatment, 1-sequence, crossover design. Pharmacokinetics (PK) and CYP2C8 genotype were assessed in healthy male subjects administered selexipag (200 μg twice daily [b.i.d.]) alone or with clopidogrel (300 mg single dose or 75 mg once daily [o.d.]). PK modelling and simulation were conducted to support dosing recommendations.

Results

Clopidogrel had a comparatively small effect on selexipag (<1.5-fold difference in any PK variable). For ACT

SUBMITTER: Axelsen LN 

PROVIDER: S-EPMC9328278 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature