Further insights into digoxin-quinidine interaction: Lack of correlation between serum digoxin concentration and inotropic state of the heart

Abstract

The digoxin-quinidine interaction was studied in nine healthy human subjects aged 26 to 31 years. A single oral dose (400 mg) of quinidine sulfate administered to subjects taking digoxin resulted in a mean (± standard error of the mean) increase within 1 to 6 hours in the serum digoxin concentration of 0.12 ± 0.01 ng/ ml (p <0.0001), an increase of 21 percent. Continued quinidine administration for 24 hours resulted in a 59 percent increase in the mean serum digoxin concentration from 0.68 ± 0.04 to 1.04 ± 0.06 ng/ ml (alpha = 0.05). At the same time, however, systolic time intervals demonstrated a lengthening of the mean left ventricular ejection time index from 406 ± 4 to 419 ± 2 ms (alpha = 0.05) and the mean Q−S 2 Index from 524 ± 6 to 532 ± 7 ms (difference not significant [NS]). When compared with the shortening of these intervals predicted from the digoxin dose-response curve if digoxin were the only variable, the lengthening actually observed for both intervals was highly significant. The negative inotropic effect of quinidine administration alone was assessed with systolic time intervals in four subjects. The left ventricular ejection time index lengthened from 419 ± 3 to 425 ± 6 ms (NS) and the Q−S 2 index from 541 ± 6 to 550 ± 7 ms (NS). Therefore, the lengthening of these intervals in subjects taking digitalis after the addition of quinidine represents more than just the negative inotropic effect of quinidine, and occurs despite the increase in serum digoxin concentration. The results of this study support the view that quinidine displaces digoxin from tissue-binding sites as a major mechanism of the interaction. Furthermore, it appears that quinidine may specifically displace digoxin from cardiac-binding sites. These results raise important questions concerning the recommendation to reduce the maintenance digoxin dose when concomitant quinidine therapy is initiated.