Levels Of Amiodarone Research Articles

Multicenter controlled observation of a low-dose regimen of amiodarone for treatment of severe ventricular arrhythmias

The clinical efficacy of a low-dosage schedule of amiodarone was tested in 58 patients with severe ventricular arrhythmias refractory to other drug treatments. The initially chosen regimen of 400 mg was effective at the end of the first controlled trial period (after 4 weeks) in 73% of the patients. The responsiveness was maintained with the smaller dosage of 200 mg in 68% of this group. The response was reestablished also in the patients who became nonresponders during the low-dose regimen when they returned to the initial (400-mg) dosage. No relation was found between clinical response and blood levels of amiodarone and of its deethylated metabolite. Adverse effects more often associated with amiodarone therapy were rare. However, careful monitoring of thyroid function allowed the detection in 10% of the patients of biochemically and functionally documented, but clinically silent, cases of hypo- or hyperthyroidism.

Peripheral neuropathy induced by amiodarone chlorhydrate: A clinicopathological study

Four cases of amiodarone neuropathy are reported. Patients presented a sensorimotor neuropathy with distal predominance. Improvement occurred after drug discontinuation. Nerve conduction velocities were significantly decreased. Other secondary effects of amiodarone were noted in two cases. In one case serum levels of amiodarone and N-monodesethylamiodarone were evaluated during and after treatment. Pathological study of nerve with morphometric evaluation was performed. Axonal degeneration changes were predominant in 3 cases. Aspects of segmental demyelination and remyelination were noted in one case and related to secondary demyelination. Numerous lysosomal inclusions were present in Schwann cells, fibroblasts, capillary endothelial and perithelial cells and in perineural cells. Similar inclusions have been observed in other drug-induced lipidosis. The factors responsible for this neuropathy are unknown. In one case, amiodarone-induced hepatic failure might explain the persisting high serum levels of the drug.

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 less than 0.01). Peak concentrations (amiodarone, 3 to 14 microgram/ml; metabolite, 0.7 microgram/ml) were attained in 4.9 +/- 1.2 hr. Using computer fits to the data, amiodarone mean elimination rate constant and half-life (t 1/2 e) 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 microgram/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 +/- 1.3 microgram/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 t 1/2 e of 29 +/- 19 days. Our kinetic data are consistent with the long therapeutic amiodarone t 1/2 noted in the treatment of cardiac arrhythmias.