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

Abstract

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.), 6.2% of the administered radioactivity was excreted in the bile. The major biliary metabolites were identified as the glucuronide conjugates of 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.