Effects of famotidine or an antacid preparation on the pharmacokinetics of nilotinib in healthy volunteers.
OBJECTIVE
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.
Oncology Clinical Pharmacology, Novartis Pharmaceuticals Corporation, Florham Park, NJ 07932, USA. opheliayin@optonline.net
Ophelia Q P
OQ
Yin
Véronique
V
Bédoucha
Tracey
T
McCulloch
Cheng
C
Zheng
Wei
W
Zhou
Azra
A
Hussaini
Steven
S
Novick
D000284:Administration, Oral; D000328:Adult; D000863:Antacids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004347:Drug Interactions; D015738:Famotidine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
D000863:Antacids; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D015738:Famotidine; C498826:nilotinib