Transient changes in plasma digoxin concentration and the development of cardiotoxicity.

1. Eight dogs were given two infusions of digoxin 0.1 mg/kg, one over 9 min and the other one over 90 min in a randomized sequence, allowing at least 12 days between each experiment. 2. Digoxin plasma profiles reflected the rate of digoxin infusion, the peak concentration of drug attained at the end of each infusion being considerably higher but more transient after the 9 min than after the 90 min transfusion. 3. Digoxin reduced the amount of acetylstrophanthidin required to produce electrocardiographic evidence of cardiotoxicity. This increase in cardiac sensitivity at 150 and at 360 min after the start of the digoxin infusion was independent of rate of infusion. 4. These results suggest that the development of cardiotoxicity is dependent upon the quantity of digoxin delivered into the systemic circulation regardless of the plasma concentration. 5. By inference, cardiotoxicity is related solely to the amount and not the rate of absorption from a given dose of digoxin.