Interactions of amiodarone with digoxin in rats.

1. The influence of oral amiodarone treatment on the blood and tissue concentrations of digoxin was investigated in the anaesthetized rat by use of unlabelled and [3H]-digoxin. 2. Amiodarone diminished the total body clearance and the apparent volume of digoxin distribution by 60%. This reduction was due to a 50% reduction of the hepatobiliary clearance, whereas the renal clearance did not change. 3. Amiodarone treatment increased blood, myocardial and skeletal muscle [3H]-digoxin concentrations by 200% indicating passive equilibration between blood and these tissues, and resulting in unaltered tissue to blood ratios. In contrast, the liver concentration increased by 70% only and the liver to blood ratio therefore decreased under amiodarone treatment. 4. It is concluded that the hepatobiliary elimination of digoxin is decreased in amiodarone-treated rats compared to controls and is responsible for the increased levels of blood and tissue glycoside.