Why the study?
Does oral amiodarone treatment alter the pharmacokinetics and tissue distribution of digoxin in rats?
Does oral amiodarone treatment alter the pharmacokinetics and tissue distribution of digoxin in rats?
In a rat model, amiodarone increases digoxin levels by reducing its hepatobiliary clearance, providing a mechanistic basis for this well-known clinical drug interaction.
Hypothesis-generating in rats; leaves open human pharmacokinetic confirmation before any dosing adjustments.
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.
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Braunschweig et al. (1987) studied this question.
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