These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: In vitro biotransformation of finasteride in rat hepatic microsomes. Isolation and characterization of metabolites.
    Author: Ishii Y, Mukoyama H, Ohtawa M.
    Journal: Drug Metab Dispos; 1994; 22(1):79-84. PubMed ID: 8149894.
    Abstract:
    Metabolism of finasteride ([N-(1,1-dimethylethyl)-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta- carboxamide]; MK-906), a new type of specific inhibitor of testosterone 5 alpha-reductase, was investigated using rat hepatic microsomes. The metabolism of finasteride by rat hepatic microsomes was oxygen- and NADPH-dependent, and addition of metyrapone, 7,8-benzoflavone, and cytochrome c to the incubation mixture inhibited the metabolism of finasteride. It is suggested that the metabolic reaction of finasteride was mediated by a mixed function oxidase involving P-450. Four major metabolites were detected in vitro on incubating finasteride with hepatic microsomes of rats treated with phenobarbital (PB-Ms), whereas two major metabolites were found in the incubation mixture with microsomes of untreated rats (UT-Ms). These metabolites were isolated and purified by solvent extraction and semi-preparative HPLC, and identified by MS spectrometry and NMR spectroscopy. The metabolites consisted of omega-hydroxy finasteride (M-1), finasteride-omega-al (M-2), finasteride-omega-oic acid (M-3), and 6 alpha-OH finasteride (M-4). M-1 and M-4 are the major metabolites in UT-Ms, and M-1 and M-3 in PB-Ms. These studies revealed that hydroxylation of the t-butyl group and ring hydroxylation at the 6-position were key steps in the metabolism of finasteride in the rat hepatic microsomes. Further, the major metabolite M-4 was hydroxylated at the 6 alpha-position, but not at the 6 beta-position of the drug. This finding suggests the existence of a novel enzyme that catalyzes the 6 alpha-hydroxylation of the 4-azasteroid.
    [Abstract] [Full Text] [Related] [New Search]