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Metabolismin vitroof warfarin by enzymic and nonenzymic systems

Authors
Journal
Biochemical Pharmacology
0006-2952
Publisher
Elsevier
Publication Date
Volume
17
Issue
8
Identifiers
DOI: 10.1016/0006-2952(68)90228-1

Abstract

Abstract The metabolism of warfarin to 6-, 7- and 8-hydroxywarfarin occurs in rat liver microsomes and requires NADPH and molecular oxygen for activity. The Michaelis constant for the three hydroxylation reactions is 1.5 × 10 − M. The enzymic hydroxylation of warfarin by liver differs from the nonenzymic hydroxylation. The enzymie metabolism by rat liver microsomes yields more 7-hydroxywarfarin than 6- or 8-hydroxywarfarin. The nonenzymic hydroxylation of warfarin by Fenton's system results in the formation of 6-hydroxywarfarin as the major hydroxylated product. The formation of an unidentified nonphenolic metabolite is also described.

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