Drug metabolism in a gut-liver microphysiological system
23 Mar 2021First-pass metabolism was modelled using the PhysioMimix® gut-liver MPS (MPS-TL6 plate) on the Core System, combining a Caco-2/HT-29 gut Transwell with PHH liver microtissues. Diclofenac dosed apically permeated the gut barrier and was metabolised to 4’-hydroxydiclofenac, with co-cultures producing more metabolite than the sum of single-organ MPS, indicating organ-organ crosstalk. Mathematical modelling (R/RxODE) supported dose and sampling optimisation for translational ADME studies.
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