1. Effect of the Proton Pump Inhibitor Esomeprazole on the Oral Absorption and Pharmacokinetics of Nilotinib.
- Author
-
Yin, Ophelia Q. P ., Gallagher, Neil, Fischer, Deirdre, Demirhan, Eren, Wei Zhou, Golor, Georg, and Schran, Horst
- Subjects
- *
BLOOD testing , *ANALYSIS of variance , *CONFIDENCE intervals , *DRUG interactions , *ENZYME inhibitors , *EXPERIMENTAL design , *GASTRIC acid , *HYDROGEN-ion concentration , *LIQUID chromatography , *MASS spectrometry , *PHYSICAL diagnosis , *RESEARCH funding , *TIME , *ESOMEPRAZOLE , *CHRONIC myeloid leukemia , *ABSORPTION , *DRUG administration , *DRUG dosage , *PHARMACOKINETICS , *DRUG therapy - Abstract
Nilotinib (Tasigna), a highly selective and potent BCRABL 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. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF