Detection of a new N-oxidized metabolite of flutamide, N-[4-nitro-3-(trifluoromethyl)phenyl]hydroxylamine, in human liver microsomes and urine of prostate cancer patients

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Rika GodaYasushi Yamazoe

Abstract

Flutamide (2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-propanamide), a nonsteroidal antiandrogen, is used in the treatment of prostate cancer but is occasionally associated with hepatic dysfunction. In the present study, the metabolism of flutamide including the formation of the possible reactive toxic metabolites was investigated using human liver microsomes and 10 isoforms of recombinant human cytochrome P450 (P450). 2-Hydroxyflutamide (OH-flutamide) and 4-nitro-3-(trifluoromethyl)phenylamine (FLU-1) were the main products of flutamide metabolism in human liver microsomes. The formation of OH-flutamide was markedly inhibited by ellipticine, an inhibitor of CYP1A1/1A2, and was mainly catalyzed by the recombinant CYP1A2. FLU-1 was also produced from OH-flutamide, but its metabolic rate was much less than that from flutamide. An inhibitor of carboxylesterase, bis-(p-nitrophenyl)phosphoric acid, completely inhibited the formation of FLU-1 from flutamide in human liver microsomes. A new metabolite, N-[4-nitro-3-(trifluoromethyl)phenyl]hydroxylamine (FLU-1-N-OH), was detected as a product of the reaction of FLU-1 with human liver microsomes and identified by comparison with the synthetic standard. The formation of FLU-1-N-OH was...Continue Reading

References

May 1, 1992·The American Journal of Medicine·J L GomezF Labrie
Jan 1, 1995·Annual Review of Microbiology·J C Spain
Oct 20, 1995·Journal of Chromatography. B, Biomedical Applications·P SanwaldJ Dow
Dec 24, 2002·Prostate Cancer and Prostatic Diseases·S OzonoY Hirao
May 16, 2006·Journal of Gastroenterology·Yasushi MatsuzakiKiyohiro Nishikawa

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Citations

Aug 25, 2012·Journal of Chemical Information and Modeling·Valérie Campagna-SlaterNicolas Moitessier
Mar 16, 2011·Drug Metabolism and Pharmacokinetics·Noriyuki Koyama, Yasushi Yamazoe
Jun 12, 2009·Drug Metabolism Reviews·Shu-Feng ZhouBalram Chowbay
Dec 5, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Hiroko HosomiTsuyoshi Yokoi
Jun 9, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Yukitaka YoshikawaTsuyoshi Yokoi
Oct 21, 2015·Toxicology and Applied Pharmacology·A SarrabayD Rouquié
Apr 19, 2011·Basic & Clinical Pharmacology & Toxicology·Anders Sonesson, Birgitte Buur Rasmussen
Oct 16, 2013·Biochemical Pharmacology·Kyotaka MutaTsuyoshi Yokoi
Mar 22, 2015·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Nehal F Farid, Nada S Abdelwahab
Mar 12, 2015·Drug Metabolism and Pharmacokinetics·Shingo OdaMiki Nakajima
Jan 27, 2018·Chemistry Central Journal·Nada S AbdelwahabNehal F Farid
Apr 23, 2010·Chemical & Pharmaceutical Bulletin·Wimal Herath, Ikhlas Ahmad Khan
Apr 16, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ping KangJames A Nieman
Oct 4, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Masato OhbuchiYasushi Yamazoe
Apr 3, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Akinobu WatanabeTsuyoshi Yokoi
Feb 16, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Atsushi IwamuraTsuyoshi Yokoi
Dec 31, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yuki KobayashiTsuyoshi Yokoi
Mar 15, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Mai ShimizuTsuyoshi Yokoi
Apr 4, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ping KangAlan Deese
Jun 9, 2021·Free Radical Research·Aušra Nemeikaitė-ČėnienėNarimantas Čėnas
Jun 8, 2021·Journal of Pharmaceutical Sciences·Akinori TakemuraKousei Ito

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