Pharmacodynamics of intravenous amiodarone in the dog

We have investigated the relationship between the myocardial disposition kinetics of amiodarone and the time course of its electrophysiologic effects in an open-chested anesthetized dog model. We observed that the maximal changes in both sinus cycle length and Wenkebach cycle length occurred about 30 min following a single intravenous dose of amiodarone or at the same time as the occurrence of the maximal myocardial concentration. The myocardial concentrations of amiodarone more closely reflect the electrophysiologic effects of amiodarone in the dog than do plasma concentrations. This difference is observable during the first 30 min following intravenous administration owing to the disequilibrium between plasma and myocardial disposition characteristics. Interanimal variability of electrophysiologic response is not accounted for by differences in myocardial concentrations.