Effect of grapefruit juice on the pharmacokinetics of nilotinib in healthy participants

J Clin Pharmacol. 2010 Feb;50(2):188-94. doi: 10.1177/0091270009336137. Epub 2009 Nov 30.

Abstract

Nilotinib (Tasigna; Novartis Pharmaceuticals) is a second-generation BCR-ABL tyrosine kinase inhibitor newly approved for the treatment of imatinib-resistant or imatinib-intolerant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia in chronic phase or accelerated phase. This study evaluated the effect of grapefruit juice on the pharmacokinetics of nilotinib in 21 healthy male participants. All participants underwent 2 study periods during which they received a single oral dose of 400 mg nilotinib with 240 mL double-strength grapefruit juice or 240 mL water in a crossover fashion. Serial blood samples were collected for the determination of serum nilotinib concentrations by a validated liquid chromatography/tandem mass spectrometry assay. Concurrent intake of grapefruit juice increased the nilotinib peak concentration (C(max)) by 60% and the area under the serum concentration-time curve (AUC(0-infinity)) by 29% but did not affect the time to reach C(max) or the elimination half-life of nilotinib. The most common adverse events were headache and vomiting, which were mild or moderate in severity, and their frequency appeared to be similar between 2 treatments. Based on the currently available information about nilotinib and the observed extent of increase in nilotinib exposure, concurrent administration of nilotinib with grapefruit juice is not recommended.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Beverages
  • Citrus paradisi*
  • Cross-Over Studies
  • Food-Drug Interactions*
  • Fusion Proteins, bcr-abl / metabolism
  • Headache / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Protein-Tyrosine Kinases / metabolism
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacokinetics*
  • Vomiting / chemically induced
  • Young Adult

Substances

  • 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
  • Antineoplastic Agents
  • Pyrimidines
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl