Glucuronidation of the broad‐spectrum antiviral drug arbidol by UGT isoforms. (24th December 2012)

• Record Type: Journal Article
• Authors: Song, Jin‐Hui; Fang, Zhong‐Ze; Zhu, Liang‐Liang; Cao, Yun‐Feng; Hu, Cui‐Min; Ge, Guang‐Bo; Zhao, De‐Wei
• Is Part Of: Journal of pharmacy and pharmacology. Volume 65:Number 4(2013:Apr.)
• Page Start: 521
• Page End: 527
• Publication Date: 2012-12-24
• Subjects: arbidol -- glucuronidation -- UDP‐glucuronosyltransferases (UGTs); Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12014
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: Objectives: The aim of this work was to identify the uridine glucuronosyltransferase (UGT) isoforms involved in the metabolism of the broad‐spectrum antiviral drug arbidol. Methods: A human liver microsome (HLM) incubation system was employed to catalyse the formation of arbidol glucuronide. The glucuronidation activity of commercially recombinant UGT isoforms towards arbidol was screened. A combination of kinetic analysis and chemical inhibition study was used to determine the UGT isoforms involved in arbidol's glucuronidation. Key findings: The arbidol glucuronide was detected when arbidol was incubated with HLMs in the presence of UDP‐glucuronic acid. The Eadie–Hofstee plot showed that glucuronidation of arbidol was best fit to the Michaelis–Menten kinetic model, and Km and apparent Vmax were calculated to be 8.0 ± 0.7 μm and 2.03 ± 0.05 nmol/min/mg protein, respectively. Assessment of a panel of recombinant UGT isoforms revealed that UGT1A1, UGT1A3 and UGT1A9 could catalyse the glucuronidation of arbidol. Kinetic analysis and chemical inhibition study demonstrated that UGT1A9 was the predominant UGT isoform involved in arbidol glucuronidation in HLMs. Conclusions: The major contribution of UGT1A9 towards arbidol glucuronidation was demonstrated in this study.