Tissue distribution of amiodarone (Cordarone) and desethylamiodarone in the rat was investigated after repeated oral application of various dosages of the drug. Serum and tissue concentrations ofBamiodarone and desethylamiodarone were assessed by high-performance liquid chromatography. The amiodarone and desethylamiodarBne serum and tissue levels obtained after repeated oral application of doses ranging from 25 to 100 mg/kg reveal that the accumulation of amiodarone and desethylamiodarone in the rat is dose-dependent. Amiodarone is preferentially distributed in decreasing order in adipose tissue, lung, thyroid gland, kidney and liver whereas its metabolite shows the highest affinity for lung then followed by kidney, thyroid gland, adipose tissue and liver. The penetration of amiodarone and desethylamiodarone into brain was poor and with all the applied dosages brain levels were in the same range as the corresponding serum levels. Desethylamiodarone serum and tissue concentrations were consistently lower than the corresponding amiodarone concentrations and varied from 5 to 78% (mean 45%) depending on the dose administered and the kind of tissue. The amiodarone tissue/serum concentration ratios were very high in adipose tissue (220-340) and moderate to high in the other tissues except brain (3-100) and indicate an extensive distribution of the drug with fat as a depot with a large storage capacity. The desethylamiodarone tissue/serum concentration ratios were very high in lung tissue (50-620), high in renal, thyroid and adipose tissue (20-390) and moderate in the other tissues except brain (3-90), respectively, and indicate an extensive distribution of the metabolite with fat as a reservoir and lung, kidney and thyroid gland, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)