Disposition of amiodarone in rats after single and multiple intra-peritoneal 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 (ip) doseof amiodarone (100 mg/kg) and 4 rats sacrificed 1, 2, 4, 6, 12, 18, 24, 36, 48 and 72 hours post dosing. The second 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 an d 8 weeks. Rats of both group were sampled for blood, heart, lung and fat a nd the concentrations of amiodarone in these samples were determined using. The elimination of amiodarone from plasma after single dose followed a bip hasic 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, respectively. The average co ncentrations of amiodarone in plasma, heart, lung and fat after single dose were 1.24 mug/ml, 1.73 mug/mg, 7.61 mug/mg and 29.01 mug/mg, respectively. The concentration of amiodarone after multiple dosing were halved within 8 .4, 5.5, 6.4 and 9.8 days, for the plasma, heart, lung and fat, respectivel y. The average concentrations of amiodarone in plasma, heart, lung and fat during multiple doses were 0.97 mug/mg, 7.63 mug/mg and 65.01 mug/mg respec tively. In conclusion, after multiple dosing, the elimination half-life of amiodarone and its fat contents were 3.7 and 2.8 times greater than that af ter single dosing. The excessive amount of amiodarone observed in fat tissu es after multiple dosing is probably the reason for the prolonged eliminati on half-life. Based on the elimination half-lives data, the time to steady state is about two weeks and the drug should be withheld for less than a mo nt if a patient required discontinuation because of serious adverse effects .