Weibin Qian1, Junichi Hasegawa1, Jie Yang1, Yusuke Endo2, Junichiro Miake1. 1. Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan. 2. ¶Advanced Medicine, Innovation and Clinical Research Center, Tottori University Hospital, Yonago 683-8504, Japan.
Abstract
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.
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.
Entities:
Keywords:
absorption; daijokito; portal vein sampling; ranitidine; rat model
Authors: S J Castle; G T Tucker; H F Woods; J C Underwood; C M Nicholson; M E Havler; C J Lewis; I R Flockhart; G Lloyd-Jones Journal: J Pharmacol Methods Date: 1985-12