Validation of UGT Inhibition Assays for DDI Assessment

ISSX 2019 -- Potential drug-drug interactions (DDI) mediated by inhibition of uridine di-phospho-glucuronosyltransferase (UGT) enzymes are of increasing focus. To complement our current CYP and Transporter DDI assessment program we have undertaken a validation of UGT-inhibition assays in multi-well plate format for the major UGT isoforms using recombinant rUGT enzymes (Supersomes) and a universal UGT inhibitor, nicardipine. The assays were developed using low levels of protein (0.01-0.25 mg/mL/5-125 pmol UGT equivalents) and a membrane activation phase using alamethacin (15 mg/mL). Following linearity experiments, results obtained are reported.