Pharma / Biotech

Itraconazole increases ibrutinib exposure ten-fold and reduces inter-individual variation – A potentially beneficial drug-drug interaction.

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Itraconazole increases ibrutinib exposure ten-fold and reduces inter-individual variation – A potentially beneficial drug-drug interaction.

Clin Transl Sci. 2019 Oct 30;:

Authors: Tapaninen T, Olkkola AM, Tornio A, Neuvonen M, Elonen E, Neuvonen PJ, Niemi M, Backman JT

Abstract
The oral bioavailability of ibrutinib is low and variable, mainly due to extensive first-pass metabolism by CYP3A4. 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 AUC0-∞ of ibrutinib 10.0-fold (90% CI 7.2-13.9; P < 0.001) and Cmax 8.8-fold (90% CI 6.3-12.1; P < 0.001). During itraconazole, the inter-subject variation for the AUC0-∞ (55%) and Cmax (53%) was around half of that during placebo (104%; 99%). In conclusion, itraconazole markedly increases ibrutinib bioavailability and decreases its inter-individual variability, offering a possibility to improved dosing accuracy and cost savings.

PMID: 31664782 [PubMed – as supplied by publisher]

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