In-Depth Characterization of EpiIntestinal Microtissue as a Model for Intestinal Drug Absorption and Metabolism in Human

The Caco-2 model is a well-accepted in vitro model for the estimation of fraction absorbed in human intestine. Due to the lack of cytochrome P450 3A4 (CYP3A4) activities, Caco-2 model is not suitable for the investigation of intestinal first-pass metabolism. The purpose of this study is to evaluate a new human intestine model, EpiIntestinal microtissues, as a tool for the prediction of oral absorption and metabolism of drugs in human intestine. The activities of relevant drug transporters and drug metabolizing enzymes, including MDR1 P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), CYP3A4, CYP2J2, UDP-glucuronosyltransferases (UGT), carboxylesterases (CES), etc., were detected in functional assays with selective substrates and inhibitors. Compared to Caco2, EpiIntestinal microtissues proved to be a more holistic model for the investigation of drug absorption and metabolism in human gastrointestinal tract.

Caco-2; EpiIntestinal (SMI-100), food toxicity, hazardous proteins, barrier integrity, inflammation, Inulin flux, LDH, horseradish peroxidase (HRP) Flux Assay, MTT assay, TEER, IL-6, IL-8; efflux, first-pass; P-gp; BCRP; drug transporter; CYP1A2, CYP2B6, CYP2J2, CYP2C8, CYP2C9, CYP2C19, CYP3A4, CYP2D6, UGT/7, SULT/7, UGT1A1, UDPglucuronosyltransferase; carboxylesterase; oral availability, MDR1 P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), carboxylesterases (CES1 CES2)

Phenacetin, Bupropion, Amodiaquine, Diclofenac, S-Mephenytoin, Testosterone, Midazolam, Dextromethorphan, 7-OH-Coumarin, β-Estradiol, Astemizol, BIBF1120, Atenolol, Atorvastatin, Buspirone, Felodipine, Indinavir, Irinotecan, Nifedipine, Oxybutynin, Qunidine, Rosuvastatin, Saquinavir, Ebastein, astemizole, CYP3cide, dabigatran etexilate, Raloxifene