Monoclonal antibodies and multifunctional cytochrome P450: Drug metabolism as paradigm

Monoclonal antibodies are reagents par excellence for analyzing the role of individual cytochrome P450 isoforms in multifunctional biological activities catalyzed by cytochrome P450 enzymes. The precision and utility of the monoclonal antibodies have heretofore been applied primarily to studies of human drag metabolism. The unique and precise specificity and high inhibitory activity toward individual cytochrome P450s make the monoclonal antibodies extraordinary tools for identifying and quantifying the role of each P450 isoform, in the metabolism of a drug or nondrug xenobiotic. The monoclonal antibodies identify drugs metabolized by individual,several, or polymorphic P450s. A comprehensive collection of monoclonol antibodies has been isolated to human P450s: 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C family, 2C19, 2D6, 2E1, 3A4/5, and 2J2. The monoclonol antibodies can also be used for identifying drugs and/or metabolites useful as markers for in vivo phenotyping. Clinical identification of a patient's phenotype, coupled with precise knowledge of a drug's metabolism, should lead to a reduction of adverse drug reactions and improved drug therapeutics, thereby promoting advances in drug discovery.