Disposition of amiodarone in rats after single and multiple intraperitoneal doses

The pharmacokinetics of amiodarone was studied after single and multiple do sing in two groups of male Wistar and Albino rats. The first group (40 rats ) received a single intraperitoneal (i.p.) dose of amiodarone (100 mg/kg) a nd 4 rats sacrificed 1,2,4,6,12,18,24,36,48 and 72 hours post dosing. The s econd group (42 rats) received amiodarone (50 mg/kg, i.p. daily) for 5 days a week for 5 weeks and 6 rats were sacrificed at 1,2,3,4,5,6 and 8 weeks. Rats of both groups were sampled for blood, heart, lung and fat and the con centrations of amiodarone in these samples were determined using High Perfo rmance Liquid Chromatography (HPLC). The elimination of amiodarone from pla sma after single dose followed a biphasic pattern with a terminal half-life of 54.7 +/-8.2 hours. The concentrations of amiodarone in the tissues were halved within 26.8, 34.9 and 37.45 hours in the heart, lung and fat, respe ctively. The average concentrations of amiodarone in plasma, heart, lung an d fat after single dose were 1.24 mug/ml,1.73 mug/mg and 29.01 mug/mg, resp ectively. The concentrations of amiodarone after multiple dosing were halve d within 8.4, 5.5, 6.4 and 9.8 days, for the plasma, heart, lung and fat, r espectively. The average concentrations of amiodarone in plasma, heart, lun g and fat during multiple doses were 0.97 mug/ml,1.41 mug/mg, 7.63 mug/mg a nd 65.01 mug/mg respectively. In conclusion, after multiple dosing, the eli mination half-life of amiodarone and its fat contents were 3.7 and 2.8 time s greater than that after single dosing. The excessive amount of amiodarone observed in fat tissues after multiple dosing is probably the reason for t he prolonged elimination half-life. Based on the elimination half-lives dat a, the time to steady state is about two weeks and the drug should be withh eld for less than a month if a patient required discontinuation because of serious adverse effects.