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Connecting the human intestine and liver
A primary jejunum and primary hepatocyte multi-organ MPS for more predictive studies of human drug ADME and oral bioavailability
Filed under: ADME and Drug bioavailability
Traditional immortalized intestinal cell lines and suspension hepatocytes have absent or low levels of metabolic enzyme expression, and thus fail to predict first pass human metabolism and oral bioavailability.
Efforts to improve the in vitro to in vivo translation of drug efficacy and safety data has led to the emergence of more human relevant microphysiological systems (MPS) that consist of multiple, fluidically linked organs1.
Here we describe a new MPS that links the jejunum (RepliGut® planar – jejunum) and liver using the PhysioMimix® Multi-organ System, with both cell types being of primary human origin. To demonstrate improved predictive capacity, we investigated two drugs where current models fail to adequately predict human ADME behaviour. Temocapril, which is a prodrug and is designed to be resistant to intestinal hydrolysis2 and midazolam, which is known to undergo intestinal clearance3.