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Probing the World of Cytochrome P450 Enzymes

Department of Pharmacy Practice and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL 32610

Variability in drug response can be attributed in part to variability in the activity of drug–metabolizing enzymes. One of the most important drugmetabolizing enzyme systems in humans is the cytochrome P450 (CYP) enzyme family, which is responsible for the oxidative metabolism of numerous endogenous compounds and xenobiotics. The clinical relevance of factors that influence CYP-mediated metabolism can be appreciated by estimating in vivo enzyme activity (i.e., the phenotype) through the use of "probe drugs," which are drugs predominately or exclusively metabolized by an individual CYP enzyme. Thus, the use of probe drugs alone or in combination (i.e., the cocktail approach) can provide an invaluable tool to explore the clinical relevance of genetic and nongenetic factors that affect CYP enzyme activity and thereby contribute substantially to variability in response to therapeutic drugs.

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