Amiodarone kinetics after oral doses

Abstract

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 (1400-1800 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, 3-14 .mu.g/ml; metabolite, 0.7 .mu.g/ml) were attained in 4.9 .+-. 1.2 h. Using computer fits to the data, amiodarone mean elimination rate constant and elimination half- life (t1/2e) were 0.128 .+-. 0.063 h-1 and 7.2 .+-. 5.0 h. 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 .mu.g/ml (range 0.92-11-99); in 3 patients simultaneous determination of concentrations of amiodarone and its metabolite revealed that concentration of the latter was .apprx. 50% of that of the parent drug during long-term therapy. In 4 patients on maintenance therapy (400-800 mg/day, serum level 1.08 .+-. 1.13 .mu.g/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 t1/2e of 29 .+-. 19 days. The kinetic data are consistent with the long therapeutic amiodarone t1/2e noted in the treatment of cardiac arrhythmias.