Effects of the Fluoroquinolone Antibacterial Drug Ciprofloxacin on Ventricular Repolarization in the Halothane-Anesthetized Guinea Pig

• Published in: Journal of Pharmacological Sciences 2013/07/20, Vol.122(3), pp.205-212
• Main Authors: Matsuo, Kazuhiro, Fujiwara, Kaori, Omuro, Naoki, Kimura, Itsuki, Kobayashi, Kazuko, Yoshio, Takashi, Takahara, Akira
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Anesthesia; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacology; Calcium Channel Blockers; ciprofloxacin; Ciprofloxacin - administration & dosage; Ciprofloxacin - adverse effects; Ciprofloxacin - blood; Ciprofloxacin - pharmacology; Dose-Response Relationship, Drug; Drug Resistance, Bacterial - drug effects; Electrocardiography - drug effects; fluoroquinolone antibiotic; Guinea Pigs; Halothane; Heart Ventricles - drug effects; Long QT Syndrome - chemically induced; monophasic action potential; Potassium Channel Blockers; QT interval; Sodium Channel Blockers; Ventricular Function - drug effects
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.13020FP

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.