Identification of human UDP-glucuronosyltransferase responsible for the glucuronidation of niflumic acid in human liver

Pharm Res. 2006 Jul;23(7):1502-8. doi: 10.1007/s11095-006-0250-5. Epub 2006 Jun 21.


Purpose: To assess the uridine diphosphate (UDP)-glucuronosyltransferase (UGT) isozymes involved in the glucuronidation of niflumic acid in human liver.

Methods: The glucuronidation activity of niflumic acid was determined in liver microsomes and recombinant UGT isozymes by incubation of niflumic acid with UDP-glucuronic acid (UDPGA).

Results: Incubation of niflumic acid with liver microsomes and UDPGA produced one peak, which was identified as a glucuronide from mass spectrometric analysis. A study involving a panel of recombinant human UGT isozymes showed that glucuronidation activity was highest in UGT1A1 among the isozymes investigated. The glucuronidation in human liver microsomes (HLMs) followed Michaelis-Menten kinetics with a Km value of 16 microM, which is similar to that found with recombinant UGT1A1. The glucuronidation activity of niflumic acid in microsomes from eight human livers significantly correlated with UGT1A1-catalyzed estradiol 3beta-glucuronidation activity (r=0.78, p<0.05). Beta-estradiol inhibited niflumic acid glucuronidation with an IC50 of 25 microM in HLMs, comparable to that for UGT1A1.

Conclusions: These findings indicate that UGT1A1 is the main isozyme involved in the glucuronidation of niflumic acid in the human liver.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / metabolism*
  • Estradiol / pharmacology
  • Glucuronides / metabolism*
  • Glucuronosyltransferase / antagonists & inhibitors
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism*
  • Humans
  • In Vitro Techniques
  • Isoenzymes / metabolism
  • Kinetics
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism*
  • Niflumic Acid / metabolism*
  • Recombinant Proteins / metabolism
  • Uridine Diphosphate Glucuronic Acid / metabolism*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Glucuronides
  • Isoenzymes
  • Recombinant Proteins
  • Uridine Diphosphate Glucuronic Acid
  • Estradiol
  • Niflumic Acid
  • UGT1A1 enzyme
  • Glucuronosyltransferase