Distribution of amiodarone and its metabolite, desethylamiodarone, in human tissues
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 antimortem plasma. There was no measurable amiodarone in brain (< 1.0 μg/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 incidence of amiodarone-induced pulmonary toxicity.
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Related Subject Headings
- Physiology
- 3214 Pharmacology and pharmaceutical sciences
- 3208 Medical physiology
- 1116 Medical Physiology
- 1115 Pharmacology and Pharmaceutical Sciences
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Physiology
- 3214 Pharmacology and pharmaceutical sciences
- 3208 Medical physiology
- 1116 Medical Physiology
- 1115 Pharmacology and Pharmaceutical Sciences