Effect of grapefruit juice on the pharmacokinetics of nilotinib in healthy participants.
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.
Yin
Ophelia Q P
OQ
Novartis Pharmaceuticals Corporation, Florham Park, NJ 07932, USA. Ophelia.yin@novartis.com
Gallagher
Neil
N
Li
Ai
A
Zhou
Wei
W
Harrell
Robert
R
Schran
Horst
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics; D001628:Beverages; D032083:Citrus paradisi; D018592:Cross-Over Studies; D018565:Food-Drug Interactions; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics*; D014839:Vomiting / Q000139:chemically induced; D055815:Young Adult
D000970:Antineoplastic Agents; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib