Establishment of a Novel In Situ Rat Model for Direct Measuring ofIntestinal Drug Absorption: Confirmation of Inhibitory Effects of Daijokito onthe Absorption of Ranitidine

Abstract

Background Daijokito (DJKT), a classical traditional Kampo andChinese medicine, has been used to treat acute pancreatitis in China. In ourprevious study, DJKT was found to reduce the area under the plasmaconcentration-time curve (AUC) of ranitidine in humans. Therefore, weestablished a novel rat model to examine the direct absorption of ranitidineafter daijokito administration.

Methods An in situ intestinal injection with portal vein sampling(IIPS) model was created to determine the rate of intestinal drug absorption.Rats were divided into two groups: the ranitidine group (R, n =6) or the ranitidine and daijokito group (RD, n = 6). Blood wascollected after intestinal injection of drugs. After the experiment, theconcentrations of ranitidine were measured by LC/MS/MS analysis.

Results The concentrations of ranitidine increased linearly withtime in both groups. Compared with the R group, the concentrations of ranitidinein RD group significantly decreased throughout the experiment.

Conclusion Co-administration of ranitidine with DJKT resulted insignificant decreases in intestinal absorption in rats. The reduction of thesystemic ranitidine concentration by co-administration of DJKT may be due, atleast in part, to the inhibition of intestinal absorption of ranitidine.