BIOTRANSFORMATION OF DIGITOXIN IN THE DOG

¹ Department of Pharmacology, University of California Medical Center, San Francisco, California

The radioactive substances excreted in bile, urine and feces by dogs given tritiated digitoxin were studied to elucidate the metabolic fate of this drug and the mechanism of its very persistent action. Intact dogs and dogs with complete biliary fistulas were given tritiated digitoxin a single intravenous dose. Paper chromatography of chloroform extracts and the chloroform-insoluble phase of urine, feces and bile was carried out and the resulting radioactivity distributions determined. Digitoxin and digoxin were the only excretion products identified in the chloroform extracts of all three biologic materials. In intact dogs digitoxin predominated in chloroform extracts of feces while digoxin predominated in similar extracts of urine. Two radioactive bands were consistently resolved in chromatograms of the chloroform-insoluble phases of urine and bile. Neither band corresponded to digitoxin or digitoxose. Hydrolysis of these water-soluble digitoxin metabolites yielded labeled products chromatographically indistinguishable from digitoxigenin and digitoxose. These results support the enterohepatic cycle concept of digitoxin excretion.