In Vitro  inhibitory effects of non‐steroidal antiinflammatory drugs on UDP‐glucuronosyltransferase 1A1‐catalysed estradiol 3 β ‐glucuronidation in human liver microsomes | Zendy

Mano Yuji | Zendy; Usui Takashi | Zendy; Kamimura Hidetaka | Zendy

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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.

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