Biliary and urinary excretion of [14C]warfarin in rabbits

1. The biliary and urinary excretion of racemic [14C]warfarin (1 mg/kg) was studied in male rabbits. 2. In the first 6 h after dosing (i.v.), of the administered radioactivity was excreted warfarin and its hydroxylated metabolites. 3. Four days after oral dosing, about 90% of the administered radioactivity was recovered in the urine. The major urinary metabolites were identified as warfarin alcohols, unchanged warfarin, 6-, 7-, and 4'-hydroxywarfarin; their structures were unequivocally confirmed by g.l.c.-mass spectrometric analysis. 4. In the rabbit, the bile was only a minor excretory route for warfarin, and only polar and bulky conjugates of the drug were eliminated by this pathway.