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

#### **Yunhai Cui 1,\* , Stephanie Claus <sup>2</sup> , David Schnell <sup>1</sup> , Frank Runge <sup>1</sup> and Caroline MacLean <sup>2</sup>**


Received: 6 April 2020; Accepted: 27 April 2020; Published: 28 April 2020

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