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Journal of Pharmacology And Experimental Therapeutics, Vol. 152, Issue 3, 372-382, 1966
Copyright © 1966 by American Society for Pharmacology and Experimental Therapeutics

THE METABOLISM OF TRITIATED DIGOXIN IN RENAL INSUFFICIENCY IN DOGS AND MAN

Frank I. Marcus 1, Peterson Anton Salel 1, Jay Scully 1, and Geeta G. Kapadia 1

1 Department of Medicine, Georgetown University Medical Division, District of Columbia General Hospital, Washington, D. C.

The metabolism of tritiated digoxin was studied in dogs with acute renal insufficiency induced by bilateral nephrectomy as well as bilateral ureter ligations. Eight-day metabolic studies were obtained in patients with chronic renal disease after a single intravenous injection of tritiated digoxin. In animals with renal insufficiency, the heart as well as other organs participated in the retention of activity. Tissues such as heart, liver, bile and small intestines which had a high level of activity in the control animals showed the greatest gain in radioactivity. More than 80% of activity in heart, liver and kidney tissue, obtained from sham-operated as well as nephrectomized animals, was eluted from an alumina column with 20% ethanol in chloroform. Filter paper chromatography of this fraction of heart and liver showed that the predominant peak of activity migrated with digoxin; lesser peaks of activity correspond to digoxigenin-mono- and bis-digitoxoside. Only one peak of activity which migrated with digoxin was found in kidney tissue. Two patients with renal disease had an impaired ability to eliminate a single intravenously administered dose of digoxin. The total urinary activity was one-half that excreted by control subjects. Fecal excretion of digoxin and metabolites was increased, but not sufficiently to compensate for the diminished renal excretion. The difference in biotransformation of digoxin in renal patients as compared to control subjects was detailed. The findings of a diminished urinary excretion of digoxin-H3 as well as renal retention of digoxin-H3 in tissues provides a metabolic basis for the observed sensitivity to digoxin in renal failure.

Accepted on December 30, 1965




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Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics.