title: Sparfloxacin but not levofloxacin or ofloxacin prolongs cardiac repolarization in rabbit Purkinje fibers.
abstract: Sparfloxacin, a fluoroquinolone antibacterial, has been reported to prolong cardiac repolarization in some patients. In this study, we have investigated the in vitro cardiac electrophysiological effects of two other fluoroquinolones, levofloxacin and ofloxacin, and compared them with those exerted by sparfloxacin. Cardiac action potentials have been recorded from rabbit Purkinje fibers using conventional glass microelectrodes. The influence of a sudden decrease in stimulation rate on repolarization is examined. It is found that ofloxacin and levofloxacin (1-100 microM) do not alter the action potential parameters even at a concentration as high as 100 microM. The stimulation rate is without effect on repolarization. On the contrary, sparfloxacin (1-100 microM) lengthens concentration-dependently the duration of action potential, this effect being significant from the concentration of 10 microM. A non significant decrease in maximal rate of rise of phase 0 depolarization was observed at the concentration of 100 microM. Under low stimulation rate, the sparfloxacin-induced prolonging effect was magnified and early afterdepolarizations occurred in one of seven fibers from the concentration of 30 microM and in four other fibers at the concentration of 100 microM. These results suggest that levofloxacin and ofloxacin had no effect on cardiac cellular electrophysiology whereas sparfloxacin exerts pure class III electrophysiological effects, which can explain the prolongation of QT interval observed clinically in some patients and might become arrhythmogenic in the presence of other predisposing factors.
authors.affiliation: Laboratoire de Pharmacologie, Faculté de Médecine, CH & U de Lille, France.
authors.forename: M M
authors.initials: MM
authors.lastname: Adamantidis
authors.forename: B M
authors.initials: BM
authors.lastname: Dumotier
authors.forename: J F
authors.initials: JF
authors.lastname: Caron
authors.forename: R
authors.initials: R
authors.lastname: Bordet
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones; D066298:In Vitro Techniques; D064704:Levofloxacin; D008297:Male; D015242:Ofloxacin / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D015363:Quinolones / Q000494:pharmacology*; D011817:Rabbits; D013237:Stereoisomerism
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D064704:Levofloxacin; D015242:Ofloxacin; C061363:sparfloxacin