Intestinal absorption kinetics of candidate drug HY152-J in rats in vivo

Abstract：Objective:To study the in situ intestinal absorption characteristics of candidate drug HY152-J in a rat model.Methods:In situ single-pass intestine perfusion model was adopted to study the absorption behaviors of HY152-J in different intestine segments.The concentrations of HY152-J in the perfusate were determined by HPLC.And we investigated the influences of intestine segments,drug concentrations,pH values of perfusate,and P-glycoprotein inhibitor on intestinal absorption of HY152-J.Results:The absorption rate constants (Ka) and apparent permeability coefficients (Paps) of HY152-J in the duodenum,jejunum,ileum and colon of rats had no obvious difference (P ＞ 0.05).Compared with the group of low concentration (25 μg· mL-1),the Ka and Papp values of HY152-J had conspicuous difference in high concentration (100 μg· mL-1) group (P ＜ 0.01) and the Papp values of HY152-J had apparent difference in moderate concentration (50 μg· mL-1) group (P ＜ 0.05).Different pH values of perfusate had no significant effect on the Ka and Papp values of HY152-J (P ＞ 0.05).And the P-gp inhibitor had little influence on the intestinal absorption of HY152-J (P ＞ 0.05).Conclusion:HY152-J can be absorbed in the whole segments of the intestine in rats,and dose not have a special absorption region.The absorption of HY152-J does not show an increase with concentrations in the range of 25 ～ 100 μg · mL-1.It preliminarily suggests that the absorption of HY152-J complies with active absorption.In addition,HY152-J might not be a substrate of P-gp.