THE METABOLISM OF DIGOXIN IN NORMAL SUBJECTS

¹ Cardiology Laboratory, Georgetown Medical Division, District of Columbia General Hospital, Washington, D. C.

Four healthy young subjects were given tritiated digoxin intravenously. Serial blood samples were analyzed for total activity. Selected samples of blood, urine and stool were partitioned by alumina column chromatography for differentiation of the digoxin fraction from the metabolites. Further identification of the digoxin fraction in urinary extracts was obtained by paper chromatography.

There was a rapid disappearance from the blood. Three minutes after injection, only 15.9% of the total dose injected remained in the blood, of which 90% was recovered in the 20% ethanol in chloroform eluate. In 1 hour, only 2.8% was present.

The main route of elimination of digoxin was by way of the kidneys. Of the total dose, 26.8% was excreted in the urine in the first 24 hours, 93.9% in the form of digoxin. The urinary half-time was 1.8 days.

The stool excretion accounted for an average of 14.8% of the dose. Metabolic products represented 14% of the dose excreted by the fecal route in the second day sample.

There was a close correlation between the calculated half-time in urine and stool to the duration of clinical effect. This suggests that data obtained in metabolic studies which show an impairment of digoxin metabolism may be reflected in an increased duration of action. Under these circumstances, a cumulative effect would be anticipated if the usual daily maintenance dose is administered.