{"doi":"10.1007/s13318-018-0467-9","title":"Effects of Ketoconazole and Rifampicin on the Pharmacokinetics of Nintedanib in Healthy Subjects","abstract":null,"journal":"European Journal of Drug Metabolism and Pharmacokinetics","year":2018,"id":637080,"datarank":0.5244761342199721,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.0,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1653971,"name":"Kristell Marzin","orcid":null,"position":1,"is_corresponding":false},{"id":1653972,"name":"Arvid Jungnik","orcid":null,"position":2,"is_corresponding":false},{"id":1653973,"name":"Ute von Wangenheim","orcid":null,"position":3,"is_corresponding":false},{"id":1653974,"name":"Claudia Dallinger","orcid":null,"position":4,"is_corresponding":false},{"id":1653970,"name":"Doreen Luedtke","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Effects of Ketoconazole and Rifampicin on the Pharmacokinetics of Nintedanib in Healthy Subjects","abstract":"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 0– ∞ ) and maximum concentration ( C max ) calculated using an analysis of variance. Geometric mean ratios and 2-sided 90% CIs were calculated. Exposure to nintedanib increased when it was administered following ketoconazole versus alone (AUC 0– ∞ : geometric mean ratio, 160.5% [90% CI, 148.2–173.7]; C max : geometric mean ratio, 179.6% [90% CI, 157.6–204.8]) and decreased when it was administered following rifampicin versus alone (AUC 0– ∞ : geometric mean ratio, 50.1% [90% CI, 47.2–53.3]; C max : geometric mean ratio, 59.8% [90% CI, 53.8–66.4]). The time to reach C max ( t max ) and half-life ( t ½ ) of nintedanib were unaffected by co-administration of ketoconazole or rifampicin. 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. 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