Effect of the Proton Pump Inhibitor Esomeprazole on the Oral Absorption and Pharmacokinetics of Nilotinib

Nilotinib (Tasigna), a highly selective and potent BCR‐ABL tyrosine kinase inhibitor (TkI), is administered orally and has pH‐dependent aqueous solubility, with lower dissolution at higher pH. This study evaluated the effect of esomeprazole on the pharmacokinetics of nilotinib in healthy participants. Twenty‐two participants (6 women, 16 men, mean age of 44.9 ± 12.9 years) were enrolled to receive nilotinib as a single oral 400‐mg dose on days 1 and 13 and esomeprazole as 40 mg once daily on days 8 to 13. Serial blood samples were collected up to 72 hours after nilotinib dosing, and nilotinib serum concentrations were determined by a validated liquid chromatography/ tandem mass spectrometry assay. Gastric pH was also monitored in all participants. When coadministered with esomeprazole, nilotinib Cmax was decreased by 27% and AUC0‐∞ decreased by 34%. Nilotinib tmax was prolonged from 4.0 to 6.0 hours, but t1/2 was not altered. Mean gastric pH was 1.0 ± 0.5 at baseline and increased to 2.79 ± 2.50, 3.98 ± 2.27, 5.30 ± 1.70, 5.38 ± 1.26, and 5.31 ± 1.42 at predose and 1, 2, 3, and 4 hours after the fifth esomeprazole dose, respectively. These results suggested a modest reduction in the rate and extent of nilotinib absorption by esomeprazole. Nilotinib is a TKI that may be used concurrently with esomeprazole or other proton pump inhibitors.