Prevalence of Non-Cytochrome P450-Mediated Metabolism in Food and Drug Administration-Approved Oral and Intravenous Drugs: 2006-2015.

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Cerny MA

Prevalence of Non-Cytochrome P450-Mediated Metabolism in Food and Drug Administration-Approved Oral and Intravenous Drugs: 2006-2015.

Drug Metab Dispos. 2016 Aug;44(8):1246-52. doi: 10.1124/dmd.116.070763. Epub 2016 Apr 15.

PubMed ID

27084892 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Difluprednate	Cytochrome P450 3A4	Protein	Humans	No	Substrate	Details