Investigation of digoxin, quinidine, and disopyramide interactions in rats utilizing parotid saliva, blood, and other tissues

Blood, parotid saliva, heart, liver, and kidney concentrations of digoxin and quinidine were determined in rats chronically treated with digoxin and in nontreated (control) rats after the administration of quinidine (20 mg/kg ip) and disopyramide (10 mg/kg ip). The results indicated that digoxin concentrations increased significantly and proportionally in parotid saliva and plasma after quinidine, but did not increase after disopyramide. With the exception of the liver, which showed an increase in digoxin concentrations, tissue concentrations of digoxin did not differ from control animals. In rats pretreated chronically with digoxin, quinidine concentrations in plasma, parotid saliva, or heart tissue did not differ significantly from control animals, but were significantly lower than controls in liver and kidney tissues. The results presented here lend additional support to the hypothesis that the increase in digoxin plasma concentration following quinidine administration is primarily due to interference with renal excretion and displacement of digoxin by quinidine binding sites. Furthermore, its was demonstrated that disopyramide has little or no effect on plasma digoxin levels in rats.