Wednesday, January 18, 2012

The New Information about Warfarin metabolite 4

Warfarin metabolites 4, Stereochemical aspects of protein binding and displacement by phenylbutazone. Warfarin metabolism may be inhibited through drug-drug interactions, including amiodarone and statins. Chromatographic examination of the extracts from β-glucuronidase-treated bile revealed the presence of warfarin and 4-, 6-, 7-, and 8-hydroxywarfarin. Warfarin and 7-hydroxywarfarin were the most abundant metabolites in the extracts.
Biotransformation stereoselectivity of warfarin was studied in the fungus Cunninghamella elegans (ATCC 36112) as a model of mammalian metabolism.
This organism was previously depicted to bring on entirely known phenolic mammalian metabolites of warfarin, including half a dozen-, 7-, 8-, and 4prime-hydroxywarfarin, and the previously unreported 3prime-hydroxywarfarin, as well as the diastereomeric warfarin alcohols, warfarin diketone, and aliphatic hydroxywarfarins.
Both aromatic hydroxylation and ketone reduction were found to be stereoselective for R-warfarin. Ketone reduction with the warfarin enantiomers exhibited a high level of product stereoselectivity in that R-warfarin was predominantly reduced to its S-alcohol, while S-warfarin followed came down in the main to the corresponding R-alcohol.

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