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High-resolution mass spectrometric investigation of the phase I and II metabolites of finasteride in pig plasma, urine and bile
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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2014 (English)In: Xenobiotica, ISSN 0049-8254, E-ISSN 1366-5928, Vol. 44, no 6, 498-510 p.Article in journal (Refereed) Published
Abstract [en]

1. The metabolite profile of the 5 alpha-reductase type II inhibitor finasteride has been studied in pig plasma, urine and bile using high-resolution mass spectrometry. The porcine biotransformation products were compared to those formed by human liver microsomes and to literature data of recently identified human in vivo metabolites. The objective of this study was to gain further evidence for the validity of using pigs for advanced, invasive drug-drug interaction studies that are not possible to perform in humans. 2. The use of high-resolution mass spectrometry with accurate mass measurements enabled identification of the metabolites by calculation of their elemental compositions as well as their fragmentation patterns. 3. There was an excellent match between the porcine and human metabolic profiles, corroborating the pig as a model of human drug metabolism. The glucuronides of the two recently described human hydroxylated metabolites MX and MY and the carboxylated metabolite M3 were identified as the major biotransformation products of finasteride in pig urine and bile. 4. Furthermore, the CYP enzymes involved in the formation of the hydroxylated metabolites were characterized. Human recombinant CYP3A4 could produce the two major hydroxylated metabolites MX and MY, whereas human recombinant CYP2D6 formed MY only.

Place, publisher, year, edition, pages
2014. Vol. 44, no 6, 498-510 p.
Keyword [en]
Bile, CYP3A4, finasteride, metabolism, pig
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-227250DOI: 10.3109/00498254.2013.866298ISI: 000336058400002OAI: oai:DiVA.org:uu-227250DiVA: diva2:731751
Available from: 2014-07-02 Created: 2014-06-24 Last updated: 2017-12-05Bibliographically approved

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Åberg, Annica TevellBondesson, UlfLennernäs, HansHedeland, Mikael

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