Thirty-eight patients with refractory supraventricular and ventricular tachyarrhythmias were administered a mean oral dosage of 400 mg amiodarone daily (200-600 mg). A high-pressure liquid chromatography method was used to measure serum concentrations of amiodarone and its metabolite desethylamiodarone after one week, one month, three months, and then at 6-month intervals. In 24 patients subcutaneous fatty tissue concentrations were also measured. The mean follow-up was 9 months (4 days to 29 months). A linear correlation was found between amiodarone and its metabolite in serum (r = 0.56, p less than 0.001) as well as in subcutaneous fatty tissue (r = 0.67, p less than 0.001). While serum concentrations were dose dependent, tissue concentrations accumulated during chronic therapy (p less than 0.01, both). Clinical efficacy was achieved in 84% of the patients. No statistically significant difference was found between responders and non-responders as regards serum and subcutaneous fatty tissue concentrations. Side effects of amiodarone occurred in 63%. The incidence of adverse effects was related to significantly higher serum and subcutaneous fatty tissue concentrations of amiodarone and its metabolite (p less than 0.001, both). Thus, although the determination of serum and subcutaneous fatty tissue concentrations does not seem to be helpful for assessing clinical efficacy of this antiarrhythmic drug, these values may predict the occurrence of adverse effects.
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