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Journal of Pharmacology And Experimental Therapeutics, Vol. 188, Issue 3, 615-623, 1974
Copyright © 1974 by American Society for Pharmacology and Experimental Therapeutics

RENAL AND GASTROINTESTINAL EXCRETION OF OUABAIN IN DOG AND MAN

Richard Selden 1, Michael N. Margolies 1, and Thomas W. Smith 1

1 Cardiac Unit, Department of Medicine, and Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

Pathways of excretion of the rapidly acting cardiac glycoside ouabain were studied in dogs and human subjects by means of a recently developed radioimmunoassay method and also by recovery of 3H counts after 3H-ouabain administration. All urine, bile and, or feces were collected for at least 4 days in dogs (ouabain plasma concentration half-life of 18 hours) and 5 days in humans (ouabain plasma concentration half-life of 22 hours) after ouabain infusion. Among four normal human subjects after single i.v. doses of 3H-ouabain and of unlabeled ouabain, cumulative urinary excretion of administered 3H counts [45.9 ± 5.2% (S.D.)] was in good agreement with urinary excretion of unlabeled ouabain as determined by radioimmunoassay (47.6 ± 2.7%). Fecal excretion of 3H counts was 32.9 ± 8.5%. Choledochostomy bile excretion of 3H counts in four patients undergoing common bile duct exploration averaged 5.4% with a wide range from 0.7 to 15.8%. Among four dogs, after single i.v. doses of 3H-ouabain, urinary excretion of 3H counts averaged 54 ± 2.3% of the i.v. dose. Biliary excretion after complete biliary diversion was only 5.2 ± 0.4%. Fecal excretion of 3H counts in two dogs with complete biliary diversion was 11.1% and 17.7% and in one dog without biliary diversion was 35%. Thus, while renal excretion is the predominant route of ouabain elimination, gastrointestional excretion is also substantial in both dog and man. In the dog, and possibly also in man, ouabain excretion into the gastrointestinal tract occurs at other sites in addition to the biliary tract.

Submitted on July 9, 1973
Accepted on October 25, 1973




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