[Development of an In Vitro System for Evaluating Intestinal Drug Disposition Using Human Induced Pluripotent Stem Cell-Derived Intestinal Epithelial Cells].

[Development of an In Vitro System for Evaluating Intestinal Drug Disposition Using Human Induced Pluripotent Stem Cell-Derived Intestinal Epithelial Cells]. Yakugaku Zasshi. 2018;138(10):1241-1247 Authors: Iwao T Abstract 　Tissues of the small intestine are crucial to understanding drug disposition because these tissues regulate the bioavailability of drugs. However, no evaluation system is currently available for precise and comprehensive analysis of intestinal pharmacokinetics. To address this, functional intestinal epithelial cells were generated from human induced pluripotent stem (iPS) cells for use in pharmacokinetic studies. An improved intestinal differentiation method was established by screening a variety of small molecule compounds against cells during differentiation. The mRNA expression levels of intestinal markers, drug transporters, and CYP3A4 were found to increase following treatment with compounds that act as inhibitors of mitogen-activated protein kinase, DNA methyltransferase, and transforming growth factor-β. Therefore, we inferred that these compounds enhanced differentiation into intestinal epithelial cells. The differentiated intestinal epithelial cells in the presence of these compounds possessed drug-metabolizing enzyme activities, such as those of CYPs, UDP-glucuronosyltransferase, and sulfotransferase. In addition, these cells had the ability to induce CYP3A4 in the presence of 1α,25-dihydroxyvitamin ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research