TY - JOUR TI - Duodenum Intestine-Chip for preclinical drug assessment in a human relevant model AU - Kasendra, Magdalena AU - Luc, Raymond AU - Yin, Jianyi AU - Manatakis, Dimitris V AU - Kulkarni, Gauri AU - Lucchesi, Carolina AU - Sliz, Josiah AU - Apostolou, Athanasia AU - Sunuwar, Laxmi AU - Obrigewitch, Jenifer AU - Jang, Kyung-Jin AU - Hamilton, Geraldine A AU - Donowitz, Mark AU - Karalis, Katia A2 - Radisic, Milica A2 - Akhmanova, Anna VL - 9 PY - 2020 DA - 2020/01/14 SP - e50135 C1 - eLife 2020;9:e50135 DO - 10.7554/eLife.50135 UR - https://doi.org/10.7554/eLife.50135 AB - Induction of intestinal drug metabolizing enzymes can complicate the development of new drugs, owing to the potential to cause drug-drug interactions (DDIs) leading to changes in pharmacokinetics, safety and efficacy. The development of a human-relevant model of the adult intestine that accurately predicts CYP450 induction could help address this challenge as species differences preclude extrapolation from animals. Here, we combined organoids and Organs-on-Chips technology to create a human Duodenum Intestine-Chip that emulates intestinal tissue architecture and functions, that are relevant for the study of drug transport, metabolism, and DDI. Duodenum Intestine-Chip demonstrates the polarized cell architecture, intestinal barrier function, presence of specialized cell subpopulations, and in vivo relevant expression, localization, and function of major intestinal drug transporters. Notably, in comparison to Caco-2, it displays improved CYP3A4 expression and induction capability. This model could enable improved in vitro to in vivo extrapolation for better predictions of human pharmacokinetics and risk of DDIs. KW - Organs-on-Chips KW - organoids KW - duodenum KW - CYP3A4 KW - drug transport KW - drug metabolism JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -