The dual orexin receptor antagonist daridorexant does not affect the pharmacokinetics of the BCRP substrate rosuvastatin.

The dual orexin receptor antagonist daridorexant does not affect the pharmacokinetics of the BCRP substrate rosuvastatin. Clin Exp Pharmacol Physiol. 2020 Jun 30;: Authors: Zenklusen I, Muehlan C, Ulc I, Liška J, Dingemanse J Abstract Daridorexant is a dual orexin receptor antagonist in clinical development for the treatment of insomnia. Breast-cancer resistant protein (BCRP) is an efflux pump expressed in intestinal epithelium and hepatocytes, contributing to the absorption, distribution, and elimination of drugs and endogenous compounds.In vitro, daridorexant inhibits BCRP with an IC50 of 3.0 μM. The BCRP substrate rosuvastatin is a cholesterol-lowering drug, recommended for clinical drug-drug interaction (DDI) studies. In order to exclude an inhibitory effect of daridorexant on BCRP, this single-centre, open-label, two-treatment Phase 1 study investigated the effect of daridorexant at steady-state on the pharmacokinetics (PK) of single-dose rosuvastatin in 20 healthy male subjects. In addition, safety and tolerability were assessed. A single oral dose of 10 mg rosuvastatin on Day 1 was followed by 96 h observation. Thereafter, 25 mg daridorexant was administered once daily (o.d.) on Day 5-8 and in combination with 10 mg rosuvastatin on Day 8. On Day 9-12, subjects received 25 mg daridorexant alone. PK sampling was performed up to 120 h after treatment administration.The results showed that concomitant administration of 25 mg dar...
Source: Clinical and Experimental Pharmacology and Physiology - Category: Drugs & Pharmacology Authors: Tags: Clin Exp Pharmacol Physiol Source Type: research