Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
It is necessary to precisely assess intestinal and hepatic first-pass effects in pharmacokinetic prediction of oral drugs, because bioavailability is a very important factor to exhibit drug efficacy and toxicity. In the pharmacokinetic studies of liver, cryopreserved human primary hepatocytes are the most used. On the other hand, human colon adenocarcinoma cell line Caco-2 are frequently used for a prediction of drug absorption in the small intestine. However, in Caco-2 cells, the expression levels of transporters and drug metabolizing enzymes are different from human intestine. We have developed the differentiation methods of human iPS cells (hiPSC) into pharmacokinetically functional small intestinal epithelial cells using small molecular compounds. Microphysiological system (MPS) has been recently developed, and utilization of the chip in the drug development is attracted attention as advanced research field of human in vitro models. We also attempted to develop MPS that can predict the first-pass effects in vitro. The probe substrates for cytochrome P450 enzymes were added in the small intestinal compartment. We sequentially collected solution from the part of corresponding to portal vein blood and hepatic vein blood, and detected substrates and its metabolites. We are expecting that hiPSC-derived cells and MPS will be used in drug evaluation systems.
