APPLICATION NOTE

Predicting oral bioavailability with PhysioMimix OOC

Improved prediction of oral bioavailability using a gut-liver microphysiological system

Application note overview:

Central to the development of all new drugs is an understanding of their pharmacokinetic (PK) properties. One of the most important properties is bioavailability, defined as the fraction of a drug that reaches systematic circulation following absorption in the gut and first-pass metabolism in the liver.

Correctly predicting drug bioavailability in humans is crucial. Estimations are required to guide the drug development process and they form the basis for setting safe and efficacious doses in the clinic. Their accuracy is therefore linked to the success, or failure, of clinical trials. Despite such importance, this key parameter is largely derived from animal models which lack human relevance.

We have developed a gut-liver microphysiological system (or organ-on-a-chip) where a 3D liver tissue, made of primary human hepatocytes, and an intestinal barrier tissue, made of epithelial and goblet cells, are interlinked by continuously flowing media. Uniquely, this enables the interplay between intestinal permeability and hepatic metabolism to be investigated in vitro. We used the gut-liver MPS to predict human bioavailability and demonstrated an improved correlation compared to animals.

Authors
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Yassen Abbas, Tomasz Kostrzewski and David Hughes

CN Bio, Cambridge, UK