期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 486, 期 2, 页码 189-200出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2003.12.014
关键词
fluoroquinolone; monophasic action potential; QT interval; torsades de pointes; atrioventricular block; alpha(1)-adrenoceptor stimulation
The proarrhythmic effects of fluoroquinolone antibacterial agents, sitafloxacin, gatifloxacin and moxifloxacin, were compared using three in vivo models. In the halothane-anesthetized dogs (n = 5), intravenous 10-min infusion of gatifloxacin and moxifloxacin (1-3 mg/kg) prolonged the ventricular effective refractory period and the repolarization period to a similar extent, whereas sitafloxacin (1-3 mg/kg) prolonged the former only. No significant change was detected in other cardiovascular parameters. In the chronic complete atrioventricular block dogs (n = 4), oral administration of 100 mg/kg of gatifloxacin (2 of 4) and moxifloxacin (3 of 4) induced torsades de pointes, which was not observed by sitafloxacin. In the alpha-chloralose-anesthetized rabbits (n = 5), intravenous 20-min infusion of 60 mg/kg of gatifloxacin induced torsades de pointes (I of 5) in the presence of methoxamine infusion, which was not observed by sitafloxacin or moxifloxacin. Thus, the halothane-anesthetized model is suitable for assessing QT prolongation, whereas the chronic complete atrioventricular block model is sensitive for detecting torsadogenic action of drugs. The alpha-chloralose-anesthetized model is the simplest and least expensive method, but its sensitivity to detect proarrhythmic action may be less great. (C) 2004 Elsevier B.V. All rights reserved.
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