Distribution of amiodarone and its metabolite, desethylamiodarone, in human tissues

Abstract

The distribution of the antiarrhythmic drug amiodarone and its principal lipophilic metabolite, desethylamiodarone, was determined in postmortem tissues of six patients who received amiodarone therapy (treatment period, 6-189 days; total dose, 4.8-127.0 g). Amiodarone concentration was highest in liver, lung, adipose tissue, and pancreas, followed by kidney, heart (left ventricle), and thyroid gland, and lowest in antemortem plasma. There was no measurable amiodarone in brain (less than 1.0 microgram/g). Desethylamiodarone concentration was highest in liver and lung, followed by pancreas, adipose tissue, kidney, heart, thyroid gland, and brain, and lowest in plasma. For most patients, the desethylamiodarone concentration was higher than the amiodarone concentration in liver, lung, kidney, heart, thyroid gland, and brain, whereas the parent drug concentration was higher than the metabolite concentration in adipose tissue, pancreas, and plasma. Tissue amiodarone and desethylamiodarone concentrations appeared to be related more closely to the total dose of amiodarone than to their respective plasma concentrations. One patient died of apparent amiodarone-induced pulmonary toxicity after an 18-day period of pharmacotherapy. Clinical evidence of pulmonary dysfunction appeared at 15 days after the initiation of amiodarone therapy, and the patient died at 23 days. Histologic assessment of a lung necropsy specimen revealed acute alveolar interstitial damage. This case represents the earliest reported incident of amiodarone-induced pulmonary toxicity.

The antiarrhythmic efficacy of amiodarone and desethylamiodarone, alone and in combination, in dogs with acute myocardial infarction.

“…18. 19 The greater tendency for desethylamiodarone to accumulate in the heart may therefore be responsible for its greater sodium channel-blocking action at a given plasma concentration compared with amiodarone.…”

Acute Renal Toxic Effect of Amiodarone in Rats

“…Moreover, several pharmacokinetics and body distribution studies have described that amiodarone and its principal metabolite, desethylamiodarone, are preferentially distributed, in decreasing order, in thyroid gland, lungs, kidneys, liver, heart, adipose tissue, skeletal muscle and brain (Riva et al 1982;Plomp et al 1985aPlomp et al , 1985bPlomp et al , 1989Brien et al 1987;Kannan et al 1991). Desethylamiodarone is the only metabolite positively identified in the plasma of patients treated with amiodarone, but no data are available on its possible pharmacological activity.…”

The Incidence and Risk of Inducing Hyperthyroidism Following Amiodarone Treatment

“…Due to isotope dilution there is a low iodine capture level in all iodine charges, but in patients with existing thyroid pathology, iodine capture is not as low as previous research shows [4,5,6].…”