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Clinical pharmacokinetics and efficacy of amiodarone for refractory tachyarrhythmias.

Abstract：

:Using a high-pressure liquid chromatographic assay, we measured serum amiodarone concentrations serially in 122 patients treated with amiodarone for 1.5-53 months (mean 9.3 months) for control of refractory symptomatic atrial or symptomatic and life-threatening ventricular tachyarrhythmias. The atrial tachyarrhythmias were successfully controlled in 45 of 54 patients (83%) during a mean follow-up of 10.0 months. In the ventricular tachyarrhythmia group, which included 22 survivors of sudden cardiac death, 38 of 50 patients (76%) responded to amiodarone during a mean follow-up of 10.9 months. Although the mean serum amiodarone concentration did not differ between responders and nonresponders, eight responders relapsed when their serum concentration fell below 1.0 mg/l. Side effects resulted in withdrawal of amiodarone in only 10 of 122 patients (9%) despite a 30% overall incidence of side effects. Central nervous system and gastrointestinal side effects became more frequent with serum concentrations greater than 2.5 mg/l, although only central nervous system side effects achieved statistical significance. Absorption and disposition kinetics of a single oral 800-mg dose of amiodarone were studied in eight patients. Serum values were measured for 24 hours in five patients during maintenance therapy, and elimination kinetics after long-term therapy were evaluated in three patients. The tissue concentration of amiodarone was determined in two patients who died during long-term amiodarone therapy and an attempt was made in 14 patients to correlate serum concentrations with daily dosages during maintenance therapy. The pharmacokinetics of oral amiodarone support the practice of using high loading dosages until arrhythmia suppression or apparent steady state is achieved (usually 2-4 weeks), followed by low-dose maintenance therapy (200-600 mg once a day) for treatment of symptomatic atrial and ventricular tachyarrhythmias.

journal_name

Circulation

journal_title

Circulation

authors

Haffajee CI,Love JC,Canada AT,Lesko LJ,Asdourian G,Alpert JS

doi

10.1161/01.cir.67.6.1347

subject

Has Abstract

pub_date

1983-06-01 00:00:00

pages

1347-55

issue

eissn

0009-7322

issn

1524-4539

journal_volume

pub_type

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Clinical pharmacokinetics and efficacy of amiodarone for refractory tachyarrhythmias.