COMPARATIVE ELECTROPHYSIOLOGIC EFFECTS OF INTRAVENOUS AMIODARONE AND DESETHYLAMIODARONE IN DOGS - EVIDENCE FOR CLINICALLY RELEVANT ACTIVITY OF THE METABOLITE
COMPARATIVE ELECTROPHYSIOLOGIC EFFECTS OF INTRAVENOUS AMIODARONE AND DESETHYLAMIODARONE IN DOGS - EVIDENCE FOR CLINICALLY RELEVANT ACTIVITY OF THE METABOLITE
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DOI：
10.1161/01.cir.75.1.265
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发表时间：
1987-01-01
期刊：
影响因子：
37.8
通讯作者：
NATTEL, S
中科院分区：
文献类型：
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作者：
TALAJIC, M;DEROODE, MR;NATTEL, S
有人认为，长期胺碘酮治疗的一些影响可能是由于代谢物去乙基胺碘酮的积累所致。为了评估代谢物的药理作用，我们给麻醉犬单次静脉注射剂量（10 或 25 mg/kg）胺碘酮或去乙基胺碘酮。两种药物的血浆和心肌浓度与人类长期口服胺碘酮治疗达到的水平相似。胺碘酮和去乙基胺碘酮导致心室和房室结传导频率依赖性减慢，并增加心房和心室不应期。这些药物对快通道和慢通道组织的相对影响不同，胺碘酮可显着延长文克巴赫周期长度，而去乙基胺碘酮可使 QRS 时限、心房不应期和心室不应期显着增加。我们得出的结论是，去乙基胺碘酮在临床相关浓度下具有显着的电生理作用，并且对体内快通道组织的影响比胺碘酮相对更大。去乙基胺碘酮的积累可能是接受长期胺碘酮治疗的患者出现一些延迟性电生理效应的原因。
It has been suggested that some of the effects of long-term amiodarone therapy may be due to accumulation of a metabolite, desethylamiodarone. To evaluate the pharmacologic actions of the metabolite, we gave single intravenous doses (10 or 25 mg/kg) of amiodarone or desethylamiodarone to anesthesized dogs. The resulting plasma and myocardial concentrations of both agents were similar to levels achieving with long-term oral amiodarone therapy in man. Amiodarone and desethylamiodarone produced frequency-dependent slowing in ventricular and atrioventricular nodal conduction and increased atrial and ventricular refractory periods. The relative effects of these agents on fast- and slow-channel tissues differed, with amiodarone producing significantly greater prolongation of Wenckebach cycle length and desethylamioadrone producing larger increases in QRS duration, atrial refractory period, and ventricular refractory period. We conclude that desethylamiodarone has substantial electrophysiologic effects at clinically relevant concentrations and has relatively greater effect on fast-channel tissue in vivo than does amiodarone. The accumulation of desethylamiodarone probable accounts for some of the delayed electrophysiologic effects in patients receiving long-term treatment with amiodarone.