P450 PHENOTYPING ASSAYS
Over the past two decades, much effort has been devoted to identifying exemplary drug substrates, or probes, whose metabolism is catalyzed specifically by a given human P450 enzyme. These metabolic probes have been distinguished using expressed recombinant P450s as well as human liver microsomes in the presence of chemical inhibitors and/or specific P450 antibodies. As such, these drugs now serve as positive controls in P450 reaction phenotyping studies performed with new chemical entities. The drug-metabolizing assays described below all meet regulatory agency requirements, and have been chosen due to their high degree of P450 enzyme specificity and ease of use. In fact, metabolite quantitation in the seven (7) assays given was performed using HPLC with UV/Vis analysis; LC/MS was not required to measure the formation of metabolites.