Non-P450 Drug-Metabolizing Enzymes: Contribution to Drug Disposition, Toxicity, and Development

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.

Automated summary

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.