Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 1, pp 219–226

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

  • Ophelia Q. P. Yin
  • Véronique Bédoucha
  • Tracey McCulloch
  • Cheng Zheng
  • Wei Zhou
  • Azra Hussaini
  • Steven Novick
Original Article

DOI: 10.1007/s00280-012-1999-3

Cite this article as:
Yin, O.Q.P., Bédoucha, V., McCulloch, T. et al. Cancer Chemother Pharmacol (2013) 71: 219. doi:10.1007/s00280-012-1999-3

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 Cmax, 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 Cmax, 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.

Keywords

Acid suppressionDrug–drug interactionH2 blockerAntacidNilotinibPharmacokinetics

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Ophelia Q. P. Yin
    • 1
  • Véronique Bédoucha
    • 3
  • Tracey McCulloch
    • 2
  • Cheng Zheng
    • 1
  • Wei Zhou
    • 4
  • Azra Hussaini
    • 5
  • Steven Novick
    • 2
  1. 1.Oncology Clinical PharmacologyNovartis Pharmaceuticals CorporationFlorham ParkUSA
  2. 2.Oncology Clinical DevelopmentNovartis Pharmaceuticals CorporationFlorham ParkUSA
  3. 3.Novartis Pharma AGBaselSwitzerland
  4. 4.Novartis Institutes for Biomedical ResearchEast HanoverUSA
  5. 5.PAREXEL Early Phase Clinical Research UnitBaltimoreUSA