Amiodarone and desethylamiodarone distribution in the atrium and adipose tissue of patients undergoing short- and long-term treatment with amiodarone

The time to onset of action of amiodarone is often long in patients treated for arrhythmias; one reason might be a slow entry of the drug into the target organ, the heart. Amiodarone and desethylamiodarone, its active metabolite, were measured in the plasma, atrial tissue and pericardial fat of patients undergoing cardiac surgery. Two groups were studied: patients treated with amiodarone for less than 28 days (short-term group) and those treated for 28 days or more (long-term group). Plasma levels of amiodarone in the two groups were not different, whereas levels of desethylamiodarone were significantly higher in the long-term group. Average concentrations of amiodarone in the atrium were higher with longer treatment periods (30.2 ± 5.6 versus 13.2 ± 2.5 μg/g wet weight of tissue); the same was true for desethylamiodarone (40.3 ± 7.7 versus 15.7 ± 3.7 μg/g). Amiodarone concentrations in fat were also significantly higher in the long-term than in the short-term group. Atrium/plasma concentration ratios of desethylamiodarone were higher than those of amiodarone, whereas fat plasma concentration ratios of desethylamiodarone were lower.In conclusion, the equilibration of amiodarone and desethylamiodarone concentrations between myocardium and plasma appears to occur slowly in patients undergoing long-term treatment with amiodarone. The higher concentration of desethylamiodarone in plasma and of desethylamiodarone and amiodarone in the atrium in the long-term group might offer an explanation for the delayed onset of the drug's antiarrhythmic action