Journal
PHARMACEUTICAL RESEARCH
Volume 23, Issue 7, Pages 1502-1508Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-006-0250-5
Keywords
glucuronidation; niflumic acid; NSAID; UGT1A1
Ask authors/readers for more resources
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 K-m value of 16 mu M, 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 3 beta-glucuronidation activity (r=0.78, p < 0.05). beta-Estradiol inhibited niflumic acid glucuronidation with an IC50 of 25 mu M 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available