A HIGH THROUGHPUT SCREENING ASSAY FOR CYP2D6 INHIBITION USING SPA n elvin Hughes

h aIntroduction The P450 cytochromes (CYP) are a superfamily of enzymes found in the liver which catalyse the oxidative conversion of drugs and other lipophilic compounds to hydrophilic metabolites. CYP2D6 and CYP3A4, catalyse the metabolism of the major proportion of drugs available on the market. Inhibition of CYP-mediated metabolism accounts for a number of adverse drug-drug interactions (1), which often leads to withdrawal from the market (2,3). A high throughput Scintillation Proximity Assay (SPA) was designed in collaboration with Merck to identify compounds that inhibit P450 CYP2D6(4). It has subsequently been developed into a high throughput screening kit (product code: CFA772)