Effects of the Fluoroquinolone Antibacterial Drug Ciprofloxacin on Ventricular Repolarization in the Halothane-Anesthetized Guinea Pig
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概要
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The fluoroquinolone antibiotic ciprofloxacin has been reported to block delayed rectifier K+ channels at much higher concentrations than those at which it exerts its bactericidal activity. In this study using the halothane-anesthetized guinea pig, we assessed whether ciprofloxacin has a proarrhythmic activity. Ciprofloxacin at a clinically relevant dose of 3 mg/kg, i.v. did not affect any electrocardiographic parameters. At 10 mg/kg, it prolonged the QT interval and the duration of the monophasic action potential of the ventricle under sinus rhythm and constant ventricular pacing (n = 6). The extents of its effects on the ventricular repolarization phase were comparable to those of another fluoroquinolone antibiotic moxifloxacin at a clinically relevant dose of 3 mg/kg (n = 6). Meanwhile, the PR interval and QRS width were also increased by ciprofloxacin at 10 mg/kg, suggesting that the drug inhibited cardiac K+ channels as well as Na+ and Ca2+ channels in vivo. These results suggest that ciprofloxacin exerted a multi-ion channel–blocking action in the heart within the supra-therapeutic dose range. Therefore, careful observation may be necessary for patients with heart disease receiving a higher dose of ciprofloxacin in order to prevent the emergence of resistance.
著者
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Matsuo Kazuhiro
Department Of Pharmacy Toho University Omori Hospital
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Kobayashi Kazuko
Department Of Cell Chemistry Okayama University Graduate School Of Medicine And Dentistry
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Fujiwara Kaori
Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Japan
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Takahara Akira
Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Japan
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Takahara Akira
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University
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Omuro Naoki
Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Japan
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Kimura Itsuki
Department of Pharmacy, Toho University Omori Medical Center, Japan
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Yoshio Takashi
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University, Japan
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Matsuo Kazuhiro
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University, Japan
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