Amiodarone concentration in human myocardium after rapid intravenous administration

Intravenous amiodarone has been found useful in the emergent management of life-threating arrhythmias. Experimental studies have shown that its electr ophysiologic effects are proportional to its myocardial concentration. Howe ver, early after its intravenous administration, the extent of the concentr ation of amiodarone in the human myocardium, the site of its action, is not well known. This study was performed to measure the myocardial concentrati on of amiodarone shortly after rapid intravenous injection. Amiodarone, 150 mg, was injected over 15 seconds intravenously into 9 patients, 52 +/- 9 y ears of age, weighing between 65 and 98 kg (mean = 81 +/- 15.6). All patien ts suffered from idiopathic dilated cardiomyopathy, were in NYHA functional class II, and the mean left ventricular ejection fraction was 21 +/- 6%. R ight ventricular endomyocardial biopsy, required for the establishment of t he diagnosis, was performed 2-5 minutes after drug administration for measu rements of its myocardial concentration. Plasma concentrations of amiodaron e were also measured at 2, 5, 10, and 60 minutes, and measurements of right heart hemodynamics were made 2 and 10 minutes after the injection. At 2.5 +/- 1.2 minutes after amiodarone administration, the mean myocardial concen tration was 95.7 +/- 67.4 mu g/g (range, 16-175), and the myocardial/plasma amiodarone ratio was 5.05 +/- 5.01. Heart rate increased from 82 +/- 17 to 90 +/- 13 beats/min (P < 0.05), and systolic blood pressure decreased from 132 +/- 19 to 118 +/- 17 mmHg (P < 0.03). The extent of myocardial fibrosi s was 5.13 +/- 6.55% (range, 0.3-17.5%). Intravenous amiodarone (150 mg) ac cumulates rapidly in the human myocardial. This pharmacokinetic characteris tic probably explains its acute efficacy in the treatment of life-threateni ng arrhythmias.