PT - JOURNAL ARTICLE AU - Kitaguchi, Takashi AU - Mizota, Taisei AU - Ito, Mina AU - Ohno, Katsutoshi AU - Kobayashi, Kazuhiro AU - Ogawa, Isamu AU - Qiu, Shimeng AU - Iwao, Takahiro AU - Hanioka, Nobumitsu AU - Tanaka, Mitsuru AU - Matsunaga, Tamihide TI - Simultaneous Evaluation of Membrane Permeability and UDP-Glucuronosyltransferase–Mediated Metabolism of Food-Derived Compounds Using Human Induced Pluripotent Stem Cell–Derived Small Intestinal Epithelial Cells AID - 10.1124/dmd.121.000605 DP - 2022 Jan 01 TA - Drug Metabolism and Disposition PG - 17--23 VI - 50 IP - 1 4099 - http://dmd.aspetjournals.org/content/50/1/17.short 4100 - http://dmd.aspetjournals.org/content/50/1/17.full SO - Drug Metab Dispos2022 Jan 01; 50 AB - Pharmacokinetic prediction after oral ingestion is important for quantitative risk assessment of food-derived compounds. To evaluate the utility of human intestinal absorption prediction, we compared the membrane permeability and metabolic activities of human induced pluripotent stem cell–derived small intestinal epithelial cells (hiPSC-SIECs) with Caco-2 cells or human primary enterocytes (hPECs). We found that membrane permeability in hiPSC-SIECs had better predictivity than that in Caco-2 cells against 21 drugs with known human intestinal availability (r = 0.830 and 0.401, respectively). Membrane permeability in hiPSC-SIECs was only 0.019–0.25-fold as compared with that in Caco-2 cells for 7 in 15 food-derived compounds, primarily those that were reported to undergo glucuronidation metabolism. The metabolic rates of the glucuronide conjugate were similar or higher in hiPSC-SIECs as compared with hPECs but lower in Caco-2 cells. Expression levels of UDP-glucuronosyltransferase (UGT) isoform mRNA in hiPSC-SIECs were similar or higher as compared with hPECs. Therefore, hiPSC-SIECs could be a useful tool for predicting human intestinal absorption to simultaneously evaluate membrane permeability and UGT-mediated metabolism.SIGNIFICANCE STATEMENT Gastrointestinal absorption is an important step for predicting the internal exposure of food-derived compounds. This research revealed that human induced pluripotent stem cell–derived small intestinal cells (hiPSC-SIECs) had better predictivity of intestinal availability than Caco-2 cells; furthermore, the metabolic rates of UDP-glucuronosyltransferase (UGT) substrates of hiPSC-SIECs were closer to those of human primary enterocytes than those of Caco-2 cells. Therefore, hiPSC-SIECs could be a useful tool for predicting human intestinal absorption to simultaneously evaluate membrane permeability and UGT-mediated metabolism.