TY - JOUR T1 - Myocardial disposition of amiodarone in the dog. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 603 LP - 608 VL - 224 IS - 3 AU - R Latini AU - S J Connolly AU - R E Kates Y1 - 1983/03/01 UR - http://jpet.aspetjournals.org/content/224/3/603.abstract N2 - 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 micrograms/ml and 0.19 to 0.43 micrograms/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. ER -