Digoxin-Quinidine Interaction: Pharmacokinetic Evaluation

Several recent reports have shown that plasma concentrations of digoxin increase when quinidine is administered along with digoxin; the present study was designed to explore the pharmacokinetics of this digoxin-quinidine interaction in six subjects. The elimination half-life of digoxin, although variable, did not change appreciably (42 vs. 44 hours) when quinidine was administered. Other pharmacokinetic values were substantially reduced in the presence of quinidine: total body clearance (from 3.08 to 1.96 ml per minute per kilogram), renal clearance (from 1.64 to 1.09 ml per minute per kilogram) and volume of distribution (from 10.87 to 7.35 liters per kilogram). The results may be explained by the displacement of digoxin from binding sites in tissue by quinidine, causing a rise in the plasma concentration of digoxin. The reduction in renal clearance of digoxin may result also from inhibition of renal secretion of digoxin by quinidine. (N Engl J Med 300:1238–1241, 1979) DIGOXIN and quinidine are frequently used in combination for the treatment of various cardiovascular disorders. Gold et al.¹ noted potential hazards with this combination 46 years ago. Recently, several reports have shown that plasma concentrations of digoxin increase approximately twofold when quinidine is administered along with digoxin.^{2 3 4 5} Hooymans and Merkus⁶ have demonstrated that quinidine reduces the renal clearance of digoxin, an effect that is consistent with the observed rise in plasma concentrations of digoxin during quinidine treatment. Recently, Straub et al.⁷ showed that quinidine reduces the number of digitalis-binding sites, as determined by in vitro binding studies with Na⁺,K.