Pharmacokinetics of intravenous amiodarone and its electrocardiographic effects on healthy Japanese subjects.
Author(s): Shiga T, Tanaka T, Irie S, Hagiwara N, Kasanuki H
Affiliation(s): Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. firstname.lastname@example.org
Publication date & source: 2011-05, Heart Vessels., 26(3):274-81. Epub 2010 Oct 30.
Publication type: Clinical Trial, Phase I; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
The aim of this phase I, dose-escalating study was to evaluate the pharmacokinetics, electrocardiographic effect and safety of amiodarone after a single intravenous administration in Japanese subjects. Thirty-two healthy Japanese male volunteers (20-32 years) were randomized to three single-dose groups (1.25, 2.5 and 5.0 mg/kg). In each group, six (1.25 mg/kg) or ten (2.5 and 5.0 mg/kg) subjects received a single 15-min infusion of intravenous amiodarone, and two subjects received glucose solution as control. The pharmacokinetic profile, blood pressure and electrocardiographic analyses were obtained on a timely basis after up to 77 days. The maximum plasma concentration (C (max)) and area under the concentration-time curve (AUC(0-96)) for amiodarone 1.25, 2.5 and 5.0 mg/kg displayed dose-dependent characteristics: mean C (max) was 2,920 +/- 610, 7,140 +/- 1,480 and 13,660 +/- 3,410 ng/ml, respectively; the mean AUC(0-96) was 3,600 +/- 700, 8,100 +/- 1,600 and 16,600 +/- 4,300 ng h/ml, respectively. A long serum half-life (>14 days) was observed for amiodarone and desethylamiodarone. PR intervals were prolonged at 15 min (0.16 +/- 0.0.1 vs. 0.15 +/- 0.01 s, p = 0.03) and 18 min (0.17 +/- 0.01 vs. 0.15 +/- 0.01 s, p = 0.03) with the 5.0 mg/kg dose compared with baseline. No other significant changes in electrocardiographic parameters, pulse rate or blood pressure were observed. A needle-pain-induced vasovagal effect appeared in a volunteer, and three volunteers experienced pain at the drug infusion site. After a single infusion of amiodarone at doses of 1.25-5.0 mg/kg, serum concentrations increased in a dose-dependent manner. A single intravenous amiodarone dose barely affected the electrocardiographic parameters and was well tolerated.