Tissue uptake and metabolism of amiodarone after chronic administration in rabbits.

This study was designed to determine serum and tissue concentrations of amiodarone and its metabolite desethylamiodarone after chronic amiodarone administration in rabbits. Rabbits were administered 20 mg/kg amiodarone for 6 weeks. Serum, liver, kidney, heart, lung, spleen, bile, adipose tissue, and muscle were collected upon sacrifice. Amiodarone and desethylamiodarone concentrations were determined in serum and tissues by an HPLC procedure standardized in our laboratory. Amiodarone concentrations were the highest in fat tissue followed by lung, liver, and muscle, with the lowest concentration in serum and only traces in the brain. Desethylamiodarone concentrations in liver, lung, and kidney approached those of the parent drug while the metabolite was present in negligible amounts in fat tissue and in brain. Bile from amiodarone-treated rabbits showed the presence of two more new metabolites which have not been characterized. Desethylamiodarone/amiodarone ratios in serum and tissues after chronic administration in rabbits were lower than in man. Nevertheless, differential accumulation of amiodarone and desethylamiodarone may be relevant to efficacy and toxicity studies.