Influence of gastrointestinal activity on the absorption of nilotinib

Abstract

Nilotinib has bioavailability (BA) of only about 25% or less. The purpose of this study was to evaluate the influence of gastrointestinal activity on the absorption of nilotinib. In order to change gastrointestinal activity, mosapride was used for enhancement and butylscopolamine was used for suppression. Experiments on oral administration of nilotinib using rats whose gastrointestinal activity was altered by mosapride or butylscopolamine were carried out. The results of oral administration of acetaminophen to rats with peristalsis movement changed showed that the effects of peristalsis and gastric emptying rate (GER) on drug absorption could be evaluated in this experimental system. Similarly, even with nilotinib, no change in Tmax was observed, but Cmax increased and decreased significantly. Due to the change in gastrointestinal activity, Cmax of nilotinib changed greatly. This showed that gastrointestinal activity affected the emulsifying action of bile and that the absorbability changed. As a result of examining the contribution to the emulsifying action, it was found that when the bile does not exist in the gastrointestinal tract, absorption of nilotinib did not change even when gastrointestinal motility was enhanced. Therefore, the results suggested that gastrointestinal activity influenced the emulsifying action of bile and the absorption of nilotinib was changed.