Digoxin quinidine interaction: a pharmacokinetic study in the isolated perfused rat liver.
Digoxin-quinidine interaction was studied in the experimental model of isolated perfused rat liver. Neither digoxin nor quinidine were toxic to the isolated rat liver. The clearance of digoxin and quinidine by the liver was directly related to the rate of bile flow and the size of the initial dose of digoxin. In the presence of quinidine, after initial doses of digoxin of 0.5 and 1 micrograms, the concentration of digoxin in the perfusate was increased 2.5 and 3-fold. Its excretion in the bile was reduced by 45% and 20.5%, respectively (all comparisons, p less than 0.01). Digoxin concentration in the liver tissue was calculated and found to be appreciably elevated in the presence of quinidine. A reduction of about 30% (p less than 0.05) in the excretion of quinidine in the bile was observed in the presence of digoxin. Thus, a competition of digoxin and quinidine for biliary excretion was demonstrated as an underlying cause for digoxin-quinidine interaction in the isolated perfused rat liver.