TY - JOUR T1 - WARFARIN METABOLISM IN THE GUINEA PIG I. Pharmacological Studies JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 704 LP - 710 VL - 1 IS - 5 AU - FRED W. DECKERT Y1 - 1973/09/01 UR - http://dmd.aspetjournals.org/content/1/5/704.abstract N2 - Warfarin metabolism in guinea pigs was studied with respect to dose, time, and animal age. For biotransformation studies 1-2 mg/kg doses of 4-14C-warfarin sodium were injected ip into young male guinea pigs. Fifty percent of the injected 14C was excreted via urine during the first 12 hr, while 86% of the dose was found there within 7 days after injection; another 9% of the dose was found in the feces. Seven urinary metabolites were identified via isotope dilution with an ether extract of the urine: Warfarin (W), 13%; 4'-OH-W, 28%; 6-OH-W, 4-5%; 7-OH-W, 2-3%; 8-OH-W, 1-2%; salicylic acid, 4%; and an intramolecular condensation product, 2,3-dihydro-2-methyl-4-phenyl-5-oxo-γ-pyrano(3,2-c)(1)benzopyran (DHG2), 4-5%. Chromatographic studies also indicated the presence of these metabolites in feces, but in different proportions. At the 1-2 mg/kg dose level, no significant age effect could be detected in the gross excretion rate of metabolites. Injecting higher warfarin levels resulted in decreased initial excretion rates, but the total percentages excreted after 5 days were roughly equal. Individual metabolites fluctuated both with respect to dose levels and time. The anticoagulant activities of warfarin and its metabolites in the guinea pig are also reported. Of the hydroxywarfarins, only 4'-OH-W showed activity at 10 mg/kg. DHG also had low potency, but led to a secondary peak of more pronounced activity. Copyright © 1973 by The American Society for Pharmacology and Experimental Therapeutics ER -