¹⁴C-Warfarin Excretion in the Rat^{[*)] [**)]}

Summary

The excretion of ¹⁴C-warfarin and its metabolites in bile and urine was studied in rats with or without biliary fistulas. After oral administration of the drug, 39.4% of the ¹⁴C could be isolated in the bile and 18.9% in the urine at the end of 96 h. After i.v. administration 47.5% and 21.3% of the ¹⁴C was found in the bile and the urine respectively. In animals without biliary fistulas, 41% of the dose was found in the urine after intravenous injection and 43% via the oral route. In bile, five radioactive components were detected; one component was identified as warfarin and represented 3.9% (oral) and 8.5% (I.V.) of the ¹⁴C in the bile. Another component of bile (17.7% to 19.6% of ¹⁴C) was identified as 6-hydroxywarfarin. In urine, three ¹⁴C components were found; the major component in urine was found to be warfarin and represented close to 75% of the ¹⁴C in the urine. Two ¹⁴C metabolites which were present in the urine were also present in the bile. Biliary fistula did not prevent radioactivity from being discharged into the urine. In feces, 9.3% of the dose could be isolated and was similar to warfarin. In the liver, at the end of four hours, 19% of the ¹⁴C could be isolated; only 74% of this could be extracted and was established as warfarin. The liver failed to show the presence of any metabolites.

^*) This investigation was supported by grant MA-3304 from the Medical Research Council of Canada.

^**) Presented in part at the XIII International Congress of Hematology, Munich, Germany, August 2-8, 1970.

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