rifampin and nintedanib

Nintedanib is a substrate for p-glycoprotein which can impact bioavailability. We investigated the effects of ketoconazole, a p-glycoprotein inhibitor, and rifampicin, a p-glycoprotein inducer, on the pharmacokinetics of nintedanib.. In the ketoconazole study, 34 healthy subjects received nintedanib 50 mg orally alone and 1 h after the last dose of ketoconazole given orally at a dose of 400 mg once daily for 3 days in 1 of 2 randomized sequences. In the rifampicin study, 26 subjects received nintedanib 150 mg orally alone and the morning after the last dose of rifampicin given orally at a dose of 600 mg once daily for 7 days. The primary objective was to determine the relative bioavailability of nintedanib administered following multiple doses of ketoconazole or rifampicin versus alone, based on AUC from time 0 extrapolated to infinity (AUC. Exposure to nintedanib increased when it was administered following ketoconazole versus alone (AUC. Exposure to nintedanib is increased by co-administration of ketoconazole and decreased by co-administration of rifampicin, likely due to effects on bioavailability of the absorbed fraction. ClinicalTrials.govidentifiers:NCT01679613, NCT01770392.

Topics: Administration, Oral; Adolescent; Adult; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Availability; Cross-Over Studies; Drug Administration Schedule; Drug Interactions; Germany; Healthy Volunteers; Humans; Indoles; Intestinal Absorption; Ketoconazole; Male; Middle Aged; Models, Biological; Rifampin; Risk Assessment; Young Adult