Abstract
Purpose
This study evaluated the effects of either famotidine or antacid on the pharmacokinetics of nilotinib in healthy subjects, with the specific focus to explore different dosing separation schemes leading to a minimized drug–drug interaction.
Methods
Fifty-two subjects were randomized to receive the following treatments in a crossover manner: (A) single oral nilotinib 400 mg alone; (B) famotidine 20 mg twice a day for 3 days, followed by a single administration of nilotinib 400 mg and famotidine 20 mg on Day 4, where famotidine was given 2 h after nilotinib; (C) single oral nilotinib 400 mg and antacid suspension 20 mL, where antacid was given 2 h before nilotinib; (D) single oral nilotinib 400 mg and antacid suspension 20 mL, where antacid was given 2 h after nilotinib.
Results
Comparing Treatment B to Treatment A, the geometric mean ratios of nilotinib C max, AUC0-tlast, and AUC0-inf were 0.966, 0.984, and 0.911, respectively (90 % confidence intervals (CIs), 0.875–1.066, 0.905–1.069, and 0.798–1.039, respectively). Nilotinib pharmacokinetic parameters following Treatment C or Treatment D were similar to those after Treatment A; the corresponding 90 % CIs of the geometric mean ratios of C max, AUC0-tlast, and AUC0-inf all fell within the bioequivalence range of 0.8–1.25.
Conclusions
Neither famotidine nor antacid significantly affected nilotinib pharmacokinetics. When concurrent use of an H2 blocker or an antacid is necessary, the H2 blocker may be administered 10 h before and 2 h after nilotinib dose, or the antacid may be administered 2 h before or 2 h after nilotinib dose.
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Acknowledgments
The authors thank the nursing and research staff members at PAREXEL for their assistance in the conduct of the clinical study and all volunteers for their participation. Medical editorial assistance in the preparation of this manuscript was provided by Erinn Goldman, PhD, and Karen Miller-Moslin, PhD, and was funded by Novartis Pharmaceuticals Corporation.
Conflict of interest
The study was supported by Novartis Pharmaceuticals Corporation. Ophelia Yin, Véronique Bédoucha, Tracey McCulloch, Cheng Zheng, Wei Zhou, and Steven Novick are employees of Novartis Pharmaceuticals Corporation.
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Yin, O.Q.P., Bédoucha, V., McCulloch, T. et al. Effects of famotidine or an antacid preparation on the pharmacokinetics of nilotinib in healthy volunteers. Cancer Chemother Pharmacol 71, 219–226 (2013). https://doi.org/10.1007/s00280-012-1999-3
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DOI: https://doi.org/10.1007/s00280-012-1999-3