%0 Journal Article %A Albert P. Li %A Novera Alam %A kirsten Amaral %A Ming-Chih David Ho %A Carol Loretz %A Walter Mitchell %A Qian Yang %T Cryopreserved human intestinal mucosal epithelium: a novel in vitro experimental system for the evaluation of enteric drug metabolism, P450 induction, and enterotoxicity %D 2018 %R 10.1124/dmd.118.082875 %J Drug Metabolism and Disposition %P dmd.118.082875 %X We report here a novel in vitro enteric experimental system, cryopreserved human intestinal mucosa (CHIM), for the evaluation of enteric drug metabolism, drug-drug interaction, drug toxicity, and pharmacology. CHIM were isolated from the small intestines of four human donors. The small intestines were first dissected into duodenum, jejunum and ileum, followed by collagenase digestion of the intestinal lumens. The isolated mucosa were gently homogenized to yield multiple cellular fragments followed by cryopreservation in a programmable liquid cell freezer and stored in liquid nitrogen. After thawing and recovery, CHIM were found to retain robust P450 and non-P450 drug metabolizing enzyme activities, to demonstrate dose-dependent induction of gene expression of CYP24A1 (approx. 300-fold) and CYP3A4 (approx. 3-fold) by vitamin D3, and induction of CYP3A4 (approx. 3-fold) by rifampin after treatment for 24 hours. Dose-dependent decreases in cell viability quantified by cellular ATP content was observed for naproxen and acetaminophen, with a higher enterotoxicity observed for naproxen, consistent with what is observed in humans in vivo. The results suggest that CHIM may be a useful in vitro experimental model for the evaluation of enteric drug properties including drug metabolism, drug-drug interactions, and drug toxicity. %U https://dmd.aspetjournals.org/content/dmd/early/2018/07/13/dmd.118.082875.full.pdf