Itraconazole Increases Ibrutinib Exposure 10‐Fold and Reduces Interindividual Variation—A Potentially Beneficial Drug‐Drug Interaction

Autor: Tuija Tapaninen, Aleksi M. Olkkola, Aleksi Tornio, Mikko Neuvonen, Erkki Elonen, Pertti J. Neuvonen, Mikko Niemi, Janne T. Backman
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Clinical and Translational Science, Vol 13, Iss 2, Pp 345-351 (2020)
Druh dokumentu: article
ISSN: 1752-8062
1752-8054
DOI: 10.1111/cts.12716
Popis: The oral bioavailability of ibrutinib is low and variable, mainly due to extensive first‐pass metabolism by cytochrome P450 (CYP) 3A4. The unpredictable exposure can compromise its safe and effective dosing. We examined the impact of itraconazole on ibrutinib pharmacokinetics. In a randomized crossover study, 11 healthy subjects were administered itraconazole 200 mg or placebo twice on day 1, and once on days 2–4. On day 3, 1 hour after itraconazole (placebo) and breakfast, ibrutinib (140 mg during placebo; 15 mg during itraconazole) was administered. Itraconazole increased the dose‐adjusted geometric mean area under the concentration‐time curve from zero to infinity (AUC0–∞) of ibrutinib 10.0‐fold (90% confidence interval (CI) 7.2–13.9; P
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje