According to the findings of a pharmacokinetics study, the concurrent administration of nilotinib with grapefruit juice is not recommended due to the risk of increase in nilotinib exposure.

The study evaluated the effect of grapefruit juice on the pharmacokinetics of nilotinib in 21 healthy male subjects who received a single oral dose of 400mg nilotinib with 240mL double-strength grapefruit juice or 240 mL water in a crossover fashion. Grapefruit juice increased the nilotinib peak concentration by 60% and the area under the serum concentration-time curve by 29% but did not affect the time to reach Cmax or the elimination half-life of nilotinib. The most common adverse events were headache and vomiting, the frequency of which appeared to be similar between 2 treatments.

The researchers conclude that grapefruit juice increased the absorption and bioavailability of nilotinib without affecting the elimination or disposition of nilotinib. They suggest that these observations are likely attributed to the decrease in CYP3A4-mediated first-pass metabolism of nilotinib in the intestine, as nilotinib metabolism is primarily mediated by CYP3A4 and the drug appears to undergo a moderate first-pass metabolism, whilst grapefruit juice, is well known to have a specific inhibitory effect on intestinal CYP3A4 activity. In addition, recent in vitro studies have demonstrated that grapefruit juice also inhibits P-gp-mediated efflux transport, which may potentially lead to increased oral bioavailability of P-gp substrates, of which nilotinib is one.