TY - JOUR T1 - Prevalence of Non–Cytochrome P450–Mediated Metabolism in Food and Drug Administration–Approved Oral and Intravenous Drugs: 2006–2015 JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1246 LP - 1252 DO - 10.1124/dmd.116.070763 VL - 44 IS - 8 AU - Matthew A. Cerny Y1 - 2016/08/01 UR - http://dmd.aspetjournals.org/content/44/8/1246.abstract N2 - In recent years, claims of increased involvement of non–cytochrome P450 (non-P450) enzymes in the metabolism of drugs have appeared in the literature. However, no temporal summaries of the contribution of non-P450 enzymes to the metabolism of drugs have been published. Using data from human radiolabeled absorption, distribution, metabolism, and excretion studies available for a set of 125 orally or intravenously administered small-molecule drugs approved by the United States Food and Drug Administration from 2006 to 2015, the contributions of P450 and non-P450 enzymes to the formation of major metabolites (≥10% of dose) were assessed and tabulated. Over this time frame, the involvement of P450 versus non-P450 enzymes in the formation of major metabolites is compared, and the individual non-P450 enzymes responsible are described. This analysis indicates that non-P450 enzymes contribute significantly to the metabolism of the 125 drugs analyzed. Approximately 30% of the metabolism of these drugs is carried out by non-P450 enzymes, with the predominant non-P450 enzymes identified being glucuronosyltransferases (11.7%), hydrolases (10.8%), carbonyl reductases (2.4%), and aldehyde oxidase (1.1%). Although significant, the relative contribution of non-P450 enzymes to drug metabolism does not appear to have increased dramatically over the last 10 years. As the current evaluation involves drugs which emerged from the discovery phase >10 years ago, this evaluation may not reflect the current or evolving situation in some research organizations; therefore, additional monitoring and assessment of the involvement of non-P450 enzymes in the metabolism of drugs will be conducted in the future. ER -