01806nas a2200325   4500000000100000008004100001260001500042653000900057653002100066653001800087653002100105100002300126700001800149700001600167700002100183700002700204700001900231700002900250700002200279700001500301700001400316700002400330700002300354245012100377856007200498300001100570490000800581520087700589022001401466       2023                            d  c2023-09-0110aADME10aDrug development10aorgan-on-chip10aPharmacokinetics1 aMarit Keuper-Navis1 aMarkus Walles1 aBirk Poller1 aAdam Myszczyszyn1 aThomas K. van der Made1 aJoanne Donkers1 aHossein Eslami Amirabadi1 aMartijn J. Wilmer1 aSaskia Aan1 aBart Spee1 aRosalinde Masereeuw1 aEvita van de Steeg00aThe application of organ-on-chip models for the prediction of human pharmacokinetic profiles during drug development  uhttps://www.sciencedirect.com/science/article/pii/S1043661823002098  a1068530 v1953 aOrgan-on-chip (OoC) technology has led to in vitro models with many new possibilities compared to conventional in vitro and in vivo models. In this review, the potential of OoC models to improve the prediction of human oral bioavailability and intrinsic clearance is discussed, with a focus on the functionality of the models and the application in current drug development practice. Multi-OoC models demonstrating the application for pharmacokinetic (PK) studies are summarized and existing challenges are identified. Physiological parameters for a minimal viable platform of a multi-OoC model to study PK are provided, together with PK specific read-outs and recommendations for relevant reference compounds to validate the model. Finally, the translation to in vivo PK profiles is discussed, which will be required to routinely apply OoC models during drug development.  a1043-6618