Pharmacokinetics of Intravenous Amiodarone in Patients with Impaired Left Ventricular Function

Vadiei, Kiumars; O'Rangers, Eleanor A.; Klamerus, Karen J.; Kluger, Jeffrey; Kazierad, David J.; Leese, Philip T.; Chow, Moses S. S.; Zimmerman, James J.

doi:10.1002/j.1552-4604.1996.tb04241.x

Cited by 12 publications

(12 citation statements)

References 21 publications

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“…This value is an underestimate because the sampling period (3 days) was completed before the terminal phase of the elimination of amiodarone was reported to begin (about 4 to 5 days after dosing 25 – 28 ). Similar reasons can be invoked to explain the more rapid than expected elimination rate of the desethyl metabolite in the present study compared to previous reports 11 , 25 – 27 . Nevertheless, the estimation error affects both treatment groups equally and does not interfere with the evaluation of relative bioavailability after intravenous administration.…”

Section: Discussionsupporting

confidence: 87%

Bioequivalence of 2 Intravenous Amiodarone Formulations in Healthy Participants

Cushing¹,

Adams²,

Cooper³

et al. 2009

The Journal of Clinical Pharma

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Intravenous amiodarone is an effective agent for the treatment of recurrent ventricular fibrillation and hemodynamically unstable ventricular tachycardia. PM101 is a new formulation of intravenous amiodarone that uses a cyclodextrin to maintain amiodarone in the aqueous phase. Eighty-eight participants were enrolled in this randomized, double-blind, crossover, bioequivalence clinical study and were treated with single doses (150 mg) of PM101 and intravenous amiodarone separated by a washout period of at least 42 days. Venous blood samples were taken periodically during the first 72 hours after dosing to determine standard pharmacokinetic parameters. The amiodarone plasma concentration-time curve observed with both formulations was virtually identical, as was the 72-hour area under the curve (AUC0-72). Similar equivalence was seen for desethylamiodarone, the active metabolite of amiodarone. The geometric ratios of the AUC0-72 for amiodarone and desethylamiodarone were 1.03 (95% confidence interval [CI], 1.00-1.06) and 1.01 (0.99-1.03), respectively. Similar geometric ratios and CIs were found for maximum plasma concentration (Cmax) and for AUC extrapolated to infinity (AUC0-infinity). Because the ratios and their CI fell between the limits of 0.8 and 1.25, bioequivalence of these 2 formulations was established. No safety concerns unique to PM101 were identified.

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Section: Discussionsupporting

confidence: 87%

Bioequivalence of 2 Intravenous Amiodarone Formulations in Healthy Participants

Cushing¹,

Adams²,

Cooper³

et al. 2009

The Journal of Clinical Pharma

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show abstract

“…The time to steady state was between 1-2 weeks, which correspond to approcimately 4 to 5 times the halflives obtained after single dose. In literature the time to steady state has not been reported precisely although it was reported in one study to be about one month (17,18,19). Because steady state is usually attained within 4-5 half-lives the elimination half-lives the elimination half-lives values obtained in this study may better reflect the disposition of amiodarone.…”

Section: Discussionmentioning

confidence: 96%

Disposition of amiodarone in rats after single and multiple intra-peritoneal doses

Najjar

2000

Eur. J. Drug Metab. Pharacokinet.

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The pharmacokinetics of amiodarone was studied after single and multiple dosing 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) 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 and 8 weeks. Rats of both group were sampled for blood, heart, lung and fat and the concentrations of amiodarone in these samples were determined using. The elimination of amiodarone from plasma 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, respectively. The average concentrations of amiodarone in plasma, heart, lung and fat after single dose were 1.24 micrograms/ml, 1.73 micrograms/mg, 7.61 micrograms/mg and 29.01 micrograms/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, respectively. The average concentrations of amiodarone in plasma, heart, lung and fat during multiple doses were 0.97 microgram/mg, 7.63 micrograms/mg and 65.01 micrograms/mg respectively. 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 after single dosing. The excessive amount of amiodarone observed in fat tissues after multiple dosing is probably the reason for the prolonged elimination 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 mont if a patient required discontinuation because of serious adverse effects.

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“…The eliminationn half-lives (~) for the drug were 8.5, 5.5, 6.4 and 9.8 days for plasma, heart, lung and fats, respectively. respectively (17). On the other hand, the half-life determined after multiple dosing is many folds longer than that determined after single dose (9).…”

Section: Multiple-doses Studymentioning

confidence: 87%

Disposition of amiodarone in rats after single and multiple intraperitoneal doses

Najjar

2001

Eur. J. Drug Metab. Pharmacokinet.

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The pharmacokinetics of amiodarone was studied after single and multiple dosing 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) 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 and 8 weeks. Rats of both groups were sampled for blood, heart, lung and fat and the concentrations of amiodarone in these samples were determined using High Performance Liquid Chromatography (HPLC). The elimination of amiodarone from plasma 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, respectively. The average concentrations of amiodarone in plasma, heart, lung and fat after single dose were 1.24 microg/ml, 1.73 microg/mg and 29.01 microg/mg, respectivelly. The concentrations 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, respectively. The average concentrations of amiodarone in plasma, heart, lung and fat during multiple doses were 0.97 microg/ml, 1.41 microg/mg, 7.63 microg/mg and 65.01 microg/mg respectively. 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 after single dosing. The excessive amount of amiodarone observed in fat tissues after multiple dosing is probably the reason for the prolonged elimination 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 month if a patient required discontinuation because of serious adverse effects.

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Pharmacokinetics of Intravenous Amiodarone in Patients with Impaired Left Ventricular Function

Cited by 12 publications

References 21 publications

Bioequivalence of 2 Intravenous Amiodarone Formulations in Healthy Participants

Bioequivalence of 2 Intravenous Amiodarone Formulations in Healthy Participants

Disposition of amiodarone in rats after single and multiple intra-peritoneal doses

Disposition of amiodarone in rats after single and multiple intraperitoneal doses

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