title: QT-prolonging effects of sparfloxacin, a fluoroquinolone antibiotic, assessed in the in vivo canine model with monophasic action potential monitoring.
abstract: Sparfloxacin, a fluoroquinolone antibacterial agent, prolongs cardiac repolarization, which may predispose to torsades de pointes. This study was designed to assess simultaneously the hemodynamic and electrophysiologic effects of sparfloxacin using the halothane-anesthetized, closed-chest in vivo canine model (n = 6). Sparfloxacin was intravenously administered in the following two doses with a pause of 20 min, a clinically relevant dose of 3.0 mg/kg/10 min and a 10 times higher dose of 30 mg/kg/10 min. After the low dose of sparfloxacin, cardiac output increased, heart rate decreased, and ventricular repolarization and refractory periods were prolonged. After the high dose, cardiac output increased, whereas heart rate and mean blood pressure decreased, and ventricular repolarization and effective refractory periods were prolonged. The increment was greater in repolarization than in refractoriness, indicating an increase of electrical vulnerability. Because sparfloxacin prolonged repolarization in a reverse use-dependent manner, its negative chronotropic effect may have potentiated the QT prolongation. Left ventricle preload, left ventricular contraction, and AV nodal as well as intraventricular conduction were minimally affected. These results suggest that caution should be used when administering sparfloxacin to patients having risk factors for QT prolongation.
authors.affiliation: Department of Medicine, Koshu Rehabilitation Hospital, Yamanashi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Satoh
authors.forename: A
authors.initials: A
authors.lastname: Sugiyama
authors.forename: K
authors.initials: K
authors.lastname: Chiba
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002036:Bundle of His / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D024841:Fluoroquinolones; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D012307:Risk Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; C061363:sparfloxacin