B.S. 1977, University of Washington Ph.D. 1981, University of California at San FranciscoThe interaction between biological systems and an administered drug are marked by a complex series of events and effects. In general, the removal of a drug from the body is accelerated by enzyme-catalyzed steps which transform the drug molecule into a series of metabolites which are more readily eliminated from the body. These biotransformation reactions occur primarily in the liver and are principally mediated by cytochrome P450 enzymes. It is now evident that the participation of the cytochrome P450 enzymes in biotransformation reactions is a two-edged sword leading to both desirable and undesirable consequences. The cytochrome P450 enzymes exhibit broad and overlapping substrate specificities and product selectivities. In addition, their distribution and levels of expression in different tissues exhibits high inter-individual variability which may be dramatically altered by exposure to drugs and environmental contaminants. As a consequence, it has often been difficult to associate a particular biochemical endpoint such as toxicity or drug clearance with a particular P450 isozyme or sub-family of isozymes. Knowledge of the role played by each isozyme is a prerequisite to understanding the participation of these enzymes in toxicity and drug metabolism.