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.
|Number of pages||6|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - 1983|
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