THE METABOLISM OF 4-C¹⁴-WARFARIN SODIUM BY THE RAT

¹ Department of Biochemistry, University of Wisconsin, Madison, Wisconsin

Warfarin and its metabolites were excreted by the rat in urine (two-thirds of the dose) and feces (one-third of the dose). For metabolic fate studies in rats, 1-mg i.p. doses of 4-C¹⁴-warfarin sodium were administered weekly. Urine and feces were collected and frozen daily during the seven days after dosing. All the urinary radioactivity was extracted and identified, using ether extraction, chromatographic (paper and thin-layer) and inverse isotope dilution techniques. The metabolites excreted in urine were unchanged warfarin (6.6% of the urinary radioactivity); several hydroxylated warfarin derivatives: 7-hydroxywarfarin (35%), 4'-hydroxywarfarin (21%), 6-hydroxywarfarin (15.4%), 8-hydroxywarfarin (8.9%), and a glucuronide of 7-hydroxywarfarin (3.9%); and an intramolecular condensation product: 2,3-dihydro-2-methyl-4-phenyl-5-oxo--pyrano(3, 2-c)(1)benzopyran (6.6%). Chromatographic data indicated the presence of these metabolites in feces but in different relative amounts than found in urine.