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

Yunhai Cui; Stephanie Claus; David Schnell; Frank Runge; Caroline MacLean

doi:10.3390/pharmaceutics12050405

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

Pharmaceutics. 2020 Apr 28;12(5):405. doi: 10.3390/pharmaceutics12050405.

Authors

Yunhai Cui¹, Stephanie Claus², David Schnell¹, Frank Runge¹, Caroline MacLean²

Affiliations

¹ Department of Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co KG, 88397 Biberach, Germany.
² Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH & Co KG, 88397 Biberach, Germany.

Abstract

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 Caco-2, EpiIntestinal microtissues proved to be a more holistic model for the investigation of drug absorption and metabolism in human gastrointestinal tract.

Keywords: BCRP; CYP3A4; Caco-2; EpiIntestinal; P-gp; UDP-glucuronosyltransferase; carboxylesterase; drug transporter; first-pass; oral availability.