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Amiodarone and desethylamiodarone tissue uptake in rats chronically treated with amiodarone is non-linear with the
Abstract:
Four groups of rats were given amiodarone chronically at 25, 37.5, 50, 75 mg kg-1/12 h for 3 weeks; on day 21 the animals were killed and blood, plasma, heart, lung, liver and fat were collected and assayed for amiodarone and desethylamiodarone. Amiodarone plasma concentrations ranged from 0.74 to 4.68 micrograms mL-1 and desethylamiodarone from 0.08 to 2.05 micrograms mL-1. Plasma, blood and tissue concentrations of amiodarone and desethylamiodarone increased significantly with the dose. Blood/plasma and tissue/plasma partition ratios of amiodarone and desethylamiodarone increased significantly at the higher doses. Blood/plasma ratio was a good predictor of tissue/plasma ratios of amiodarone and its metabolite, except in fat. Total phospholipid concentrations in lung were correlated with amiodarone and desethylamiodarone concentrations in plasma, blood and lung.