The application of organ-on-chip models for the prediction of human pharmacokinetic profiles during drug development

Organ-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 fu...

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Bibliographic Details
Published in:Pharmacological research 2023-09, Vol.195, p.106853-106853, Article 106853
Main Authors: Keuper-Navis, Marit, Walles, Markus, Poller, Birk, Myszczyszyn, Adam, van der Made, Thomas K., Donkers, Joanne, Eslami Amirabadi, Hossein, Wilmer, Martijn J., Aan, Saskia, Spee, Bart, Masereeuw, Rosalinde, van de Steeg, Evita
Format: Article
Language:English
Subjects:
ADME
Drug development
Organ-on-chip
Pharmacokinetics
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Summary:Organ-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. [Display omitted]
ISSN:1043-6618
1096-1186
DOI:10.1016/j.phrs.2023.106853