Myocardial disposition of amiodarone in the dog

The time course of myocardial uptake and disposition of amiodarone was studied after both acute i.v. and chronic oral administration. In addition, the myocardial disposition of a metabolite, N-desethylamiodarone, was studied after chronic oral amiodarone administration. After i.v. administration, the plasma concentrations of amiodarone fell rapidly; however, peak myocardial concentrations were not observed until 10 to 30 min after administration. Amiodarone was highly concentrated in the myocardium; the average (± S.D.) myocardial/plasma concentration ratio between 2 and 6 hr after administration was 89 ± 32. Although there was significant interanimal variability, there was relative consistency over time in the ratio for each dog during this time period. Although no metabolite (N-desethylamiodarone) was detected in the plasma after the single i.v. dose, it was present in both plasma and myocardial samples after chronic oral therapy. Mean steady-state plasma concentrations of amiodarone and N-desethylamiodarone ranged from 0.62 to 1.63 μg/ml and 0.19 to 0.43 μg/ml, respectively. These studies show that the myocardial disposition kinetics of amiodarone are different from other drugs studied and both amiodarone and its N-desethyl metabolite accumulate extensively in the myocardium.