Drug glucuronidation assays on human liver microsomes immobilized on microfluidic flow-through reactors

UDP-glucuronosyltransferases (UGTs), located in the endoplasmic reticulum of liver cells, are an important family enzymes, responsible for biotransformation several endogenous and exogenous chemicals, including therapeutic drugs. However, phenomenon 'latency', i.e., full UGT activity revealed by disruption microsomal membrane, poses substantial challenges predicting drug clearance based on vitro glucuronidation assays. This work introduces a microfluidic reactor design comprising immobilized human microsomes to facilitate study UGT-mediated under flow-through conditions. The performance microreactor is characterized using 8-hydroxyquinoline (via multiple UGTs) zidovudine UGT2B7) as model reactions. With help alamethicin albumin effects, we show that conducting metabolism assays flow conditions facilitates in-depth mechanistic studies, which may also shed light latency.