QUINIDINE-DIGOXIN INTERACTION - PHARMACOKINETICS, UNDERLYING MECHANISM AND CLINICAL IMPLICATIONS

Administration of quinidine with digoxin increased serum digoxin concentrations in 79 patients and five volunteers. In 38 patients on a constant glycoside maintenance dose, the addition of quinidine to digoxin therapy resulted in a mean 2.5-fold increase (from 0.98±0.37 to 2.47±0.71 ng per milliliter, mean ±1 S.D.) (P<0.001). The addition of quinidine decreased renal glycoside clearance (from 91.6±27.8 to 40.6±15.8 ml per minute) (P<0.001). Unlike other investigations, our studies provided no evidence that quinidine displaced digoxin at specific cardiac binding sites. The elevated digoxin levels found during quinidine administration suggest a 30 to 50 per cent reduction of the digoxin dose. Adverse reactions to combined quinidine — digoxin therapy may be partly due to digitalis intoxication. (N Engl J Med 301:400–404, 1979) FOR half a century many cardiac arrhythmias have been successfully treated by the combined use of quinidine and digoxin, despite the considerable risk of adverse reactions.1 Recently, surprisingly high serum digoxin concentrations have been observed during concomitant quinidine therapy.2 3 4 Extensive in vitro and in vivo investigations have excluded the possibility that quinidine or its metabolites cause false-positive values.2 3 4 The purpose of this investigation was to quantify the interaction between quinidine and digoxin. Materials and Methods Patients The study group included 79 adult patients taking digitalis and quinidine by mouth for various rhythm disorders. The mean age of these 50 men. © 1979, Massachusetts Medical Society. All rights reserved.