ABSTRACT
Identification of an amiodarone metabolite in the plasma of patients receiving a single dose of the drug was carried out by mass-spectrometry following extraction and HPLC separation. The kinetics of the plasma concentrations of unchanged compound and its identified metabolite (N-monodesthyl-amiodarone) were studied in six patients after a single administration of amiodarone by oral or intravenous routes, using a sensitive and specific high-performance liquid chromatographic method. The observed plasma clearance rate for the drug varied from 0.2 to 0.5 1.h-1.kg-1 of body weight; and the elimination half-life of the unchanged compound was found to be approximately 21 hours. Oral bioavailability, as determined in one patient, was about 60%. The proportion of the metabolite found in the plasma following a single oral administration was significantly higher than that observed after infusion. The ratio of areas under the curves for metabolite-to-unchanged compound was 0.55 and 0.13 for oral and intravenous doses respectively. During a circumscribed study carried out in five patients receiving oral doses of the drug (daily dose varied from 2.6 to 9.3 mg/kg) accumulation of the metabolite was observed. The mean of the plasma level ratios (metabolite to-unaltered drug) obtained in five patients was approximately 0.97.