Abstract

The metabolism of tritiated digoxin was studied in 14 dogs. The drug was given orally as follows: "loading dose" group, 0.75 mg on the 1st day and 0.2 mg daily thereafter for 5 days; "0.2 mg maintenance" group, 0.2 mg daily for 6 days; and "0.1 mg maintenance" group, 0.1 mg daily for 6 days. Serial blood samples were drawn. Twenty-four-hour urine and stool collections were made for 6 days. One day after the last dose of digoxin, the animals were sacrificed. Radioactivity was determined in the heart, liver, kidneys, skeletal muscle and bile. Chemical extraction, column and paper chromatography of these specimens were also performed. Twenty-four hours after the beginning of digoxin administration, the blood concentration of radioactivity was considerably greater in the loading-dose group than in the other two groups. However, by the end of 6 days, there was no statistical difference in the radioactivity present in the blood of the loading-dose group as compared with that in the 0.2-mg-maintenance group. There was no significant difference in concentration of radioactivity in heart, liver or skeletal muscle obtained from the loading-dose group and the 0.2-mg-maintenance group. However, in the kidney, skeletal muscle and probably in the heart, the concentration of activity was less in the 0.1-mg-maintenance group as compared with the 0.2-mg-maintenance group. The data are consistent with the hypothesis that the daily excretion of digoxin occurs as a function of the drug present in the body. In canine tissue, tritiated digoxin appears to be present largely in unchanged form and is excreted as such in the urine. Considerable biotransformation of digoxin is evident in the bile. The clinical implications of these experiments are that the initiation of digitalis therapy by a loading dose is not necessary to achieve cumulation of digoxin.