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  • Tevell, AnnicaUppsala universitet,Institutionen för läkemedelskemi,Analytisk Farmaceutisk kemi (författare)

Flutamide metabolism in four different species in vitro and identification of flutamide metabolites in human patient urine by high performance liquid chromatography/tandem mass spectrometry

  • Artikel/kapitelEngelska2006

Förlag, utgivningsår, omfång ...

  • 2006-03-15
  • American Society for Pharmacology & Experimental Therapeutics (ASPET),2006

Nummerbeteckningar

  • LIBRIS-ID:oai:gup.ub.gu.se/53917
  • https://gup.ub.gu.se/publication/53917URI
  • https://doi.org/10.1124/dmd.105.008516DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-80893URI

Kompletterande språkuppgifter

  • Språk:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • A new metabolic scheme of flutamide is proposed in this article. Some patients treated with flutamide, a nonsteroidal antiandrogen, have developed severe hepatic dysfunction. Toxic metabolites have been proposed to be responsible for these negative effects. In this study, the qualitative aspects of the in vitro metabolism of flutamide in liver microsomes from human, dog, pig, and rat were evaluated. A direct comparison of the flutamide metabolism in liver and prostate microsomes from pig was made, and the in vivo metabolism of flutamide was investigated in urine from orally treated prostate cancer patients. Liquid chromatography/tandem mass spectrometry was used for analysis. The mass spectrometer was equipped with an electrospray interface and operated in the negative ion mode. In liver microsomes from pig, dog, and rat, extensive hydroxylation of flutamide occurred. One, two, or three hydroxy groups were attached, and isomeric forms were detected for both monohydroxylated and trihydroxylated drug. In pig liver microsomes, isomers of a third metabolite, hydroxylated 4-nitro-3-(trifluoromethyl)-aniline, were also found after incubation with either flutamide or 2-hydroxyflutamide. In human liver microsomes, the pharmacologically active 2-hydroxyflutamide was the only metabolite detected. Several phase I metabolites as well as four intact phase II metabolites could be recovered from the urine samples. For the first time in humans, glucuronic acid conjugates of hydroxylated 4-nitro-3-(trifluoromethyl)-aniline, and mono- and dihydroxylated flutamide were identified, together with hydroxylated 4-nitro-3-(trifluoromethyl)-aniline conjugated with sulfate. In addition, one mercapturic acid conjugate of hydroxylated flutamide, probably formed from flutamide via a reactive intermediate, was detected.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Lennernäs, HansUppsala universitet,Institutionen för farmaci(Swepub:uu)hanslenn (författare)
  • Jonsson, M. (författare)
  • Norlin, MariaUppsala universitet,Institutionen för farmaceutisk biovetenskap,Farm biokemi(Swepub:uu)mno24506 (författare)
  • Lennernäs, Bo,1963Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences(Swepub:gu)xlennb (författare)
  • Bondesson, UlfUppsala universitet,Institutionen för läkemedelskemi,Analytisk Farmaceutisk Kemi(Swepub:uu)ulfbonde (författare)
  • Hedeland, Mikael (författare)
  • Uppsala universitetInstitutionen för läkemedelskemi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Drug Metab Dispos: American Society for Pharmacology & Experimental Therapeutics (ASPET)34:6, s. 984-920090-9556
  • Ingår i:Drug Metabolism and Disposition: American Society for Pharmacology & Experimental Therapeutics (ASPET)34:6, s. 984-921521-009X

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