COMPARATIVE ASSESSMENT OF PRURIFLOXACIN, SPARFLOXACIN, GATIFLOXACIN AND LEVOFLOXACIN IN THE RABBIT MODEL OF PROARRHYTHMIA
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概要
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The administration of certain quinolone antibiotics has been associated with a prolongation of the QT interval on electrocardiogram, and in rare cases ventricular arrhythmias such as torsades de pointes. In this in vivo study using a rabbit arrhythmia model, we assessed the proarrhythmic effects and changes in the QT interval elicited by the administration of NM394 (UFX), an active metabolite of the new quinolone antibiotic prulifloxacin, and three representative quinolones, sparfloxacin (SPFX), gatifloxacin (GFLX) and levofloxacin (LVFX). Chloralose-anesthetized rabbits were co-administered a continuous infusion of methoxamine (15 μg/kg/min) together with NaOH (vehicle, 0.2 mol/L), SPFX (2, 3, 4 mg/kg/min), GFLX (4 mg/kg/min), LVFX (4 mg/kg/min) or UFX (4 mg/kg/min) via the ear vein, and then the effects on electrocardiogram were examined. SPFX and GFLX both prolonged the QT and QTc intervals. GFLX also induced premature ventricular contractions in all 6 rabbits that received it, and subsequently it induced torsades de pointes (TdP) in 3 of the 6 rabbits. SPFX infused at the dose of 4 mg/kg/min induced conduction blocks without inducing TdP, whereas that infused at the lower dose of 3 mg/kg/min induced both conduction blocks and TdP. The infusions with LVFX and UFX did not elicit remarkable prolongations in the QT interval, and none of the animals infused with the agents developed arrhythmia. These findings suggested that LVFX and UFX were less potent than SPFX and GFLX in prolonging the QT interval and inducing life-threatening arrhythmias.
- 日本トキシコロジー学会の論文
- 2004-02-26
著者
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Shimo T
National Inst. Health Sci. Tokyo
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KUROSAWA Tohru
Toxicology and Pharmacokinetics Research Labs., Pharmaceutical Research Center, Meiji Seika Kaisha,
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Izumi Masaaki
Toxicology Laboratory Pharmaceutical Development Department Meiji Seika Kaisha Ltd.
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Izumi Masaaki
Toxicology & Pharmacokinetics Research Labs. Pharmaceutical Development Department Meiji Seika K
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SHODA Toshiyuki
National Institute of Health Sciences
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SAKAI Toki
Toxicology Lab., Meiji Seika Kaisha.Ltd.
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HIRATSUKA Kazuyuki
Toxicology Lab., Meiji Seika Kaisha Ltd.
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SHIBAZAKI Yoshiaki
Toxicology Lab., Meiji Seika Kaisha Ltd.
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Sakai Toki
Toxicology Lab. Meiji Seika Kaisha.ltd.
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Sakai Toki
Toxicology Laboratory Pharmaceutical Development Department Meiji Seika Kaisha Ltd.
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Shindo Yasuhiro
Toxicology Laboratory, Pharmaceutical Development Dept., Meiji Seika Kaisha, Ltd.
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Hiratsuka Kazuyuki
Toxicology Laboratory Pharmaceutical Development Department Meiji Seika Kaisha Ltd.
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Hiratsuka Kazuyuki
Toxicology Lab. Meiji Seika Kaisha Ltd.
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Shindo Yasuhiro
Toxicology Laboratory Pharmaceutical Development Department Meiji Seika Kaisha Ltd.
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Shindo Yasuhiro
Toxicology Lab. Meiji Seika Kaisha Ltd.
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Akita Megumi
Toxicology Laboratory Pharmaceutical Development Department Meiji Seika Kaisha Ltd.
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Kurosawa Tohru
Toxicology Laboratory Pharmaceutical Development Department Meiji Seika Kaisha Ltd.
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Sakai T
Yamanouchi Pharmaceutical Co. Ltd.
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Hiratsuka Kazuyuki
Division Of Plant Biotechnology Graduate School Of Environment And Information Sciences Yokohama Nat
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Shibazaki Yoshiaki
Toxicology Lab. Meiji Seika Kaisha Ltd.
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Shibazaki Yoshiaki
Toxicology Laboratory, Pharmaceutical Development Department, Meiji Seika Kaisha, Ltd.
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