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Drug Metabolism Letters

Editor-in-Chief

ISSN (Print): 1872-3128
ISSN (Online): 1874-0758

Research Article

Formation of a Toxic Quinoneimine Metabolite from Diclofenac: A Quantum Chemical Study

Author(s): Muthusamy Ramesh* and Prasad V. Bharatam

Volume 13, Issue 1, 2019

Page: [64 - 76] Pages: 13

DOI: 10.2174/1872312812666180913120736

Abstract

Background: Diclofenac is a non-steroidal antiinflammatory drug. It is predominantly metabolized by CYP2C9. 4'-hydroxydiclofenac and its quinoneimine are the metabolites of diclofenac. However, few numbers of serious cases of idiosyncratic hepatotoxicity due to diclofenac metabolism were reported. The formation of the quinoneimine metabolite was found to be responsible for this idiosyncratic toxicity. Quinoneimine is an over-oxidized metabolite of diclofenac.

Method: In this work, computational studies were conducted to detail the formation of a quinoneimine metabolite from diclofenac. Further, the idiosyncratic toxicity of quinoneimine due to its reactivity was also investigated by quantum chemical analysis.

Results & Conclusion: The results demonstrate the possibility of formation of quinoneimine metabolite due to various factors that are involved in the metabolism of diclofenac. The present study may provide the structural in-sights during the drug development processes to avoid the metabolism directed idiosyncratic toxicity.

Keywords: Quantum chemical analysis, quinoneimine, diclofenac, idiosyncratic toxicity, CYP2C9, non-steroidal antiinflammatory drug.

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