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Improved prediction of oral bioavailability using a gut-liver microphysiological system
Filed under: ADME, Drug absorption, Drug bioavailability, and Drug metabolism
About this application note:
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.
Dr Yassen Abbas, Dr Tomasz Kostrzewski & Dr David Hughes