Quinidine-induced changes in serum and skeletal muscle digoxin concentration; evidence of saturable binding of digoxin to skeletal muscle.

Eleven patients with atrial fibrillation on maintenance digoxin therapy were investigated by analysis of serum (SDC) and skeletal muscle (SMDC) digoxin concentrations before and 24 h and 2 weeks after starting quinidine treatment. After cardioversion the maintenance dose of digoxin was reduced in order to obtain the same steady-state SDC after 2 weeks, as before quinidine. SDC was increased by quinidine therapy from 1.56 to 2.40 nmol/l after 24 h. With the reduced digoxin dose SDC was 1.68 nmol/l after 2 weeks. The ratio SMDC/SDC decreased after 24 h of quinidine treatment from 35.4 to 29.0 (p less than 0.01). After 2 weeks of quinidine treatment with the reduced digoxin dose, the ratio had risen to 38.1, which did not differ significantly from the initial ratio. The present data suggest that the reduced skeletal muscle binding of digoxin during quinidine therapy is due to saturation of digoxin binding sites secondary to the increase in the total body load of digoxin at steady-state, and not to direct interference by quinidine with digoxin binding sites.