Tissue digoxin concentrations during the quinidine-digoxin interaction

Abstract

Digoxin concentrations in serum, myocardium, 3 separate skeletal muscles, kidney, liver, and 5 sites in the brain were measured in 26 dogs given 12-alpha 3H-digoxin. Ten of the dogs also received 200 mg of quinidine sulfate orally 3 times daily for 3 days, and 6 others received 240 mg of quinidine gluconate intravenously every 3 hours for 24 hours. Mean serum quinidine concentration was 6.7 ± 1.5 μg/ml in the dogs treated with quinidine for 24 hours and 3.6 ± 2.3 in the dogs treated with quinidine for 3 days (p < 0.01). Mean serum digoxin concentrations were 2.72 ± 0.88 ng/ml in dogs treated with digoxin only, 2.61 ± 0.45 in dogs treated with quinidine for 24 hours (difference not significant [NS]), and 3.20 ± 0.92 in dogs that received quinidine for 3 days (NS). In dogs treated with quinidine for 3 days, serum digoxin concentration correlated significantly with serum quinidine concentration (r = 0.76), indicating that quinidine did affect the serum digoxin concentration. No differences in tissue digoxin concentrations were found between either of the groups of dogs that received quinidine and the group that received digoxin alone. Tissue-to-serum digoxin concentration ratios were significantly different in 4 of the tissues studied in the group of dogs that received quinidine for 24 hours. In this group, the ratio of myocardial-to-serum digoxin concentration was higher (p < 0.01) and ratios of renal (p < 0.05), occipital muscle (p < 0.01), and medullary brainstem (p < 0.01) digoxin concentrations were lower. The ratio of renal-to-serum digoxin concentration decreased as serum quinidine concentration increased (r = −0.63). No correlation was found between serum quinidine concentration and tissue-to-serum digoxin concentration ratio for other tissues. Thus, in contrast to the findings in a previous study, there is no evidence of increased concentration of digoxin in the brain or of decreased digoxin concentration in the myocardium when quinidine is given to dogs receiving digoxin. The relationship of serum-to-tissue digoxin concentration changes in some tissues after 24 hours of quinidine administration. The decrease in the ratio of renal-to-serum digoxin concentration suggests that the decrease in renal digoxin clearance with quinidine is due to failure of digoxin to enter the kidney rather than to a block in the excretion of digoxin present in the kidney.