rifampin and selexipag

Based on in vitro data, there is evidence to suggest that cytochrome P450 (CYP) 2C8 is involved in the metabolism of selexipag and its active metabolite, ACT-333679. The present study evaluated the possible pharmacokinetic interactions of selexipag with gemfibrozil, a strong CYP2C8 inhibitor, and rifampicin, an inducer of CYP2C8.. The study consisted of two independent parts, each conducted according to an open-label, randomized, crossover design. The pharmacokinetics and safety of selexipag and ACT-333679 were studied following single-dose administration either alone or in the presence of multiple-dose gemfibrozil (part I) or rifampicin (part II) in healthy male subjects.. Gemfibrozil had comparatively small effects on selexipag (less than 2-fold difference in any pharmacokinetic variable) but, with respect to ACT-333679, increased the maximum plasma concentration (C. Concomitant administration of selexipag and strong inhibitors of CYP2C8 must be avoided, whereas when coadministered with inducers of CYP2C8, dose adjustments of selexipag should be envisaged.

Topics: Acetamides; Acetates; Activation, Metabolic; Adolescent; Adult; Antihypertensive Agents; Area Under Curve; Cross-Over Studies; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C8 Inhibitors; Drug Interactions; Gemfibrozil; Germany; Half-Life; Healthy Volunteers; Humans; Male; Metabolic Clearance Rate; Middle Aged; Prodrugs; Pyrazines; Rifampin; Risk Assessment; Young Adult