Effect of Macitentan on the Pharmacokinetics of the Breast Cancer Resistance Protein Substrates, Rosuvastatin and Riociguat, in Healthy Male Subjects

• DOI: 10.1007/s40261-019-00857-7
• Publication Date: 2019-09-24T20:02:31Z
• Authors: Dénes Csonka; Shirin Bruderer; Armin Schultz; Marianne Soergel; Radka Stepanova; Giancarlo Sabattini; Juan Jose Perez-R...
• Keywords: Riociguat; Rosuvastatin Calcium; Concomitant

Macitentan is a clinically approved endothelin receptor antagonist for the treatment of pulmonary arterial hypertension (PAH). Increasing use combination drug therapy in PAH means that it important to recognize potential drug-drug interactions (DDIs) could affect efficacy and safety macitentan patients with PAH.Two Phase 1 studies were conducted investigate effect at steady-state on pharmacokinetics breast cancer resistance protein (BCRP) substrates, rosuvastatin riociguat healthy male subjects. Another objective was determine tolerability concomitant administration or macitentan.Healthy subjects received single oral dose 10 mg (n = 20) Day (reference treatment). A loading 30 administered 5 followed by once-daily from 6 15 (riociguat study) 16 (rosuvastatin study). (test Pharmacokinetics evaluated 96 h after 144 168 10. To compare reference test treatments, geometric mean ratio calculated maximum plasma concentration (Cmax), area under concentration-time curve (AUC) zero (pre-dose) time last measured above limit quantification (AUC0-t), AUC infinity (AUC0-∞) terminal elimination half-life (t½) rosuvastatin, riociguat's metabolite, M1. The difference reach (tmax) determined Wilcoxon test. Trough levels its ACT-132577, monitored throughout.Ninety percent confidence intervals ratios within bioequivalence criteria 0.80-1.25. There no significant between tmax. Rosuvastatin did not concentrations ACT-132577. adverse event profile consistent known profiles drugs.Macitentan BCRP EudraCT numbers: 2017-003095-31 2017-003502-41.