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In Vitro inhibitory effects of non‐steroidal antiinflammatory drugs on UDP‐glucuronosyltransferase 1A1‐catalysed estradiol 3 β ‐glucuronidation in human liver microsomes
Author(s) -
Mano Yuji,
Usui Takashi,
Kamimura Hidetaka
Publication year - 2005
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.430
Subject(s) - glucuronidation , diflunisal , niflumic acid , naproxen , chemistry , ketoprofen , diclofenac , pharmacology , microsome , ic50 , acetaminophen , in vitro , biochemistry , chromatography , medicine , alternative medicine , pathology
The inhibitory potencies of non‐steroidal antiinflammatory drugs (NSAID) on UDP‐glucuronosyltransferase (UGT) 1A1‐catalysed estradiol 3 β ‐glucuronidation (E3G) were investigated in human liver microsomes (HLM). Inhibitory effects of the following seven NSAID were investigated: acetaminophen, diclofenac, diflunisal, indomethacin, ketoprofen, naproxen and niflumic acid. Niflumic acid had the most potent inhibitory effect on E3G with an IC 50 value of 22.2 µ M in HLM. The IC 50 values of diclofenac, diflunisal, indomethacin for E3G were 60.9, 37.8 and 51.5 µ M , respectively, while acetaminophen, ketoprofen and naproxen showed less potent inhibition. Diclofenac inhibited E3G non‐competitively with a K i value of 112 µ M in HLM. The IC 50 value of diclofenac for 4‐methylumbelliferone glucuronidation in recombinant human UGT1A1 was 57.5 µ M , similar to that obtained for E3G using HLM. In conclusion, niflumic acid had the most potent inhibitory effects on UGT1A1‐catalysed E3G in HLM among seven NSAID investigated. Copyright © 2004 John Wiley & Sons, Ltd.