Effects of famotidine or an antacid preparation on the pharmacokinetics of nilotinib in healthy volunteers.

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), AUC(0-tlast), and AUC(0-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), AUC(0-tlast), and AUC(0-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.