Cytochrome P450 Enzymes and Drug—Drug Interactions: An Update on the Superfamily

Abstract

Objective: To provide an update of the biological characteristics of cytochrome P450 (CYP) enzymes and appreciate the implications of such in the prediction and assessment of drug–drug interactions (DDIs). Data Sources: Searches of MEDLINE (1966–July 2005) and Web sites plus manual review of journals, conference proceedings, and reference textbooks were performed using the key search terms cytochrome P450 and drug–drug interaction. Study Selection/Data Extraction: All articles identified from the data sources were evaluated, and information deemed relevant was included for this review. Data Synthesis: During the past few years, significant strides have been made in our understanding of the biology of CYP enzymes and our ability to accurately assess and predict the occurrence of CYP enzyme–related pharmacokinetic DDIs. Once considered a single enzyme, the enzymes of the CYP superfamily are now recognized to exhibit highly variable substrate specificity and intriguing cooperativity with other enzymes and transporter proteins (eg, P-glycoprotein). Mechanisms of enzyme induction and inhibition have been further characterized, and the clinical implications of this knowledge require a more thorough understanding of the topic by healthcare practitioners. Conclusions: We offer a contemporary survey of the biology of CYP enzymes, including mechanisms of enzyme induction and inhibition, and encourage the incorporation of this knowledge into the assessment and prediction of DDIs in the clinical setting.