Establishment of a Novel In Situ Rat Model for Direct Measuring of Intestinal Drug Absorption: Confirmation of Inhibitory Effects of Daijokito on the Absorption of Ranitidine

Background: Daijokito (DJKT), a classical traditional Kampo and Chinese medicine, has been used to treat acute pancreatitis in China. In our previous study, DJKT was found to reduce the area under the plasma concentration-time curve (AUC) of ranitidine in humans. Therefore, we established a novel rat model to examine the direct absorption of ranitidine after 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 was collected after intestinal injection of drugs. After the experiment, the concentrations of ranitidine were measured by LC/MS/MS analysis.

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

Conclusion: Co-administration of ranitidine with DJKT resulted in significant decreases in intestinal absorption in rats. The reduction of the systemic ranitidine concentration by co-administration of DJKT may be due, at least in part, to the inhibition of intestinal absorption of ranitidine.