Digitoxin-Quinidine Interaction: Pharmacokinetic Evaluation

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Abstract
The effect of quinidine on digitoxin single-dose pharmacokinetics was evaluated in 5 healthy adults. Blood was collected for 3 wk, and a complete urine collection was obtained for 4 days after a single i.v. dose of digitoxin. The protocol was conducted once while each subject was taking oral quinidine for 3 wk, and then repeated 10 days after discontinuing quinidine treatment. Quinidine induced changes in digitoxin pharmacokinetics. Elimination half-life was prolonged from 174 .+-. 25 to 261 .+-. 58 h (P < 0.02); total body clearance decreased from 1.54 .+-. 0.40 to 1.09 .+-. 0.31 ml/h per kg (P < 0.05); renal clearance decreased from 0.65 .+-. 0.07 to 0.46 .+-. 0.17 ml/h per kg (P < 0.05). Digitoxin volume of distribution and protein binding were unaltered by quinidine. Quinidine caused a rise in serum digitoxin levels. Digitoxin total body clearance was decreased by quinidine to an extent comparable to that reported for digoxin; the mechanisms of the interaction with the 2 digitalis glycosides may, in part, be different.

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