Digitoxin-Quinidine Interaction: Pharmacokinetic Evaluation

The effect of quinidine on digitoxin single-dose pharmacokinetics was evaluated in five healthy adults. Blood was collected for 3 weeks, and a complete urine collection was obtained for 4 days, after a single intravenous dose of digitoxin. The protocol was conducted once while each subject was taking oral quinidine, for 3 weeks, and then repeated 10 days after discontinuing quinidine treatment. Quinidine induced the following changes in digitoxin pharmacokinetics: Elimination half-life was prolonged from 174 ± 25 to 261 ± 58 hours (p < 0.02); total body clearance decreased from 1.54 ± 0.40 to 1.09 ± 0.31 mL/h · kg (p < 0.05); renal clearance decreased from 0.65 ± 0.07 to 0.46 ± 0.17 mL/h 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; however, the mechanism of the interaction with the two digitalis glycosides may, in part, be different.