Amiodarone kinetics after oral doses

Amiodarone serum kinetics after single oral doses and after long-term therapy were investigated in patients with ventricular tachyarrhythmias. When amiodarone was given as a single oral dose (1400 to 1800 mg, n = 6), serum levels of amiodarone and its metabolite, measured by high-performance liquid chromatography, correlated (r = 0.69, P < 0.01). Peak concentrations (amiodarone, 3 to 14 μg/ml; metabolite, 0.7 μg/ml) were attained in 4.9 ± 1.2 hr. Using computer fits to the data, amiodarone mean elimination rate constant and half-life (t½e) were 0.128 ± 0.063 hr−1 and 7.2 ± 5.0 hr. In 12 patients given a mean dose of 1327 ± 338 mg/day of amiodarone for 4.1 ± 2.3 wk, mean serum amiodarone level was 3.84 ± 2.92 μg/ml (range 0.92 to 11.99); in three patients simultaneous determination of concentrations of amiodarone and its metabolite revealed that concentration of the latter was about 50% of that of the parent drug during long-term therapy. In four patients on maintenance therapy (400 to 800 mg/day, serum level 1.08 ± 1.13 μg / ml) drug was discontinued and serum amiodarone levels were determined serially. Serum drug disappearance followed a single exponential function with an elimination rate constant of 0.030 ± 0.012 day−1 and t½e of 29 ± 19 days. Our kinetic data are consistent with the long therapeutic amiodarone tl/2 noted in the treatment of cardiac arrhythmias. Clinical Pharmacology and Therapeutics (1982) 31, 438–444; doi:10.1038/clpt.1982.57