Journal
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
Volume 62, Issue -, Pages 405-425Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-052220-105907
Keywords
phase I metabolism; oxidation; reduction; hydrolysis; non-P450 enzymes; drug development
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This review provides an overview of the metabolism of clinically used drugs and highlights the roles of cytochrome P450 enzymes and non-P450 phase I enzymes in drug metabolism. It emphasizes the importance of studying non-P450 phase I enzymes for improving drug efficacy and reducing adverse reactions.
Most clinically used drugs are metabolized in the body via oxidation, reduction, or hydrolysis reactions, which are considered phase I reactions. Cytochrome P450 (P450) enzymes, which primarily catalyze oxidation reactions, contribute to the metabolism of over 50% of clinically used drugs. In the last few decades, the function and regulation of P450s have been extensively studied, whereas the characterization of non-P450 phase I enzymes is still incomplete. Recent studies suggest that approximately 30% of drug metabolism is carried out by non-P450 enzymes. This review summarizes current knowledge of non-P450 phase I enzymes, focusing on their roles in controlling drug efficacy and adverse reactions as an important aspect of drug development.
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