Digitoxin-quinidine interaction: pharmacokinetic evaluation

• Published in: Annals of internal medicine Vol. 93; no. 5; p. 698
• Main Authors: Fenster, P E, Powell, J R, Graves, P E, Conrad, K A, Hager, W D, Goldman, S, Marcus, F I
• Format: Journal Article
• Language: English
• Published: United States 01.11.1980
• Subjects: Adult; Digitoxin - blood; Digitoxin - metabolism; Drug Interactions; Half-Life; Humans; Mathematics; Protein Binding; Quinidine - administration & dosage; Quinidine - pharmacology
• ISSN: 0003-4819
• DOI: 10.7326/0003-4819-93-5-698

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 less than 0.02); total body clearance decreased from 1.54 +/- 0.40 to 1.09 +/- 0.31 mL/h . kg (p less than 0.05); renal clearance decreased from 0.65 +/- 0.07 to 0.46 +/- 0.17 mL/h . kg (p less than 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.