1 The tendency of a given oral dose of
digoxin to induce
cardiac dysrhythmia was determined indirectly at various times after its administration to eight conscious dogs by measurement of the intravenous dose of
acetylstrophanthidin necessary to induce toxic changes in the ECG. Acetyl-
strophanthidin was used because its rapid elimination from the body permitted estimates to be made 45, 180 and 360 min after
digoxin administration. 2 Each dog underwent four studies in which doses of 0.05, 0.1, 0.2 and 0.4 mg/kg
digoxin were used in a randomized sequence allowing at least ten days between each dose. 3
Digoxin reduced the amount of
acetylstrophanthidin required to cause toxic changes in the ECG; this increase in cardiac sensitivity was dose-dependent. 4 There was no correlation between plasma levels of
digoxin and the tendency to dysrhythmia, since peak plasma concentrations of
digoxin were reached at about 60 min after dosing whereas maximal sensitivity to
acetylstrophanthidin was found 3 to 6 h after administration of
digoxin. 5 These results suggest that there is little or no increased risk of
cardiotoxicity during periods of transient increase in plasma levels of
digoxin.