Effect of quinidine on the hepatic uptake of digoxin in guinea pigs

Effect of quinidine on the hepatic uptake of digoxin was studied using isolated guinea pig hepatocytes and with the multiple indicator dilution method using perfused livers. The initial uptake rate of digoxin by isolated hepatocytes was significantly (p less than 0.05) decreased in the presence of quinidine or ouabain and at low temperature (27 degrees C). The influx rate constant to the liver (K1) of unbound digoxin was also decreased by quinidine or the metabolic inhibitor 2,4 dinitrophenol (DNP) in isolated perfused livers, while K1 of diazepam, which is thought to be taken up by a passive transport system, was not significantly changed in the presence of DNP. These findings suggest that an active transport system for digoxin may exist in the liver and may be inhibited by quinidine. We concluded that the quinidine-induce decreases in the hepatic distribution of digoxin may be attributed both to the decreased tissue binding and to the inhibition of uptake, which might be related to the decreased hepatic clearance.