title: Glucuronidation of the broad-spectrum antiviral drug arbidol by UGT isoforms.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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 K(m) and apparent V(max) 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.
authors.affiliation: Orthopedics Department, Affiliated Zhongshan Hospital of Dalian University, Dalian, China. zhaodewei2000@163.com
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Song
authors.forename: Zhong-Ze
authors.initials: ZZ
authors.lastname: Fang
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: Zhu
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Cao
authors.forename: Cui-Min
authors.initials: CM
authors.lastname: Hu
authors.forename: Guang-Bo
authors.initials: GB
authors.lastname: Ge
authors.forename: De-Wei
authors.initials: DW
authors.lastname: Zhao
mesh_terms: D000738:Androsterone / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000069347:Erlotinib Hydrochloride; D020719:Glucuronides / Q000737:chemistry / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008528:Mefenamic Acid / Q000494:pharmacology; D050217:Metabolic Detoxication, Phase II; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D000090264:UDP-Glucuronosyltransferase 1A9; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism; D000099148:UGT1A1 Enzyme; D013440:Sulfides
chemical_list: D000738:Androsterone; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D000069347:Erlotinib Hydrochloride; D020719:Glucuronides; D014453:Glucuronosyltransferase; D007211:Indoles; D007527:Isoenzymes; D008528:Mefenamic Acid; D011799:Quinazolines; D011994:Recombinant Proteins; D000090264:UDP-Glucuronosyltransferase 1A9; D014535:Uridine Diphosphate Glucuronic Acid; D000099148:UGT1A1 Enzyme; C000715591:UGT1A9 protein, human; C086979:umifenovir; D013440:Sulfides; C122075:UDP-glucuronosyltransferase, UGT1A3