title: Azithromycin Can Prolong QT Interval and Suppress Ventricular Contraction, but Will Not Induce Torsade de Pointes.
abstract: Azithromycin has been reported to increase the risk of death from cardiovascular causes among patients with high baseline risk. Since the information is still limited to bridge the gap between electrophysiological properties of azithromycin in vitro and cardiac death in patients, we initially assessed its electropharmacological effects in doses of 3 and 30 mg/kg, i.v., with the halothane-anesthetized dogs (n = 4). The low dose provided 5.2 times higher than the therapeutic concentration, whereas the high dose attained 17.0 times higher. The high dose delayed the ventricular repolarization in a reverse use-dependent manner, reflecting blockade of the rapid component of delayed rectifier K(+) current, and the potency was relatively weak; namely, maximum change in QTc was +20 ms (+5.6%). The high dose also induced the negative inotropic effect possibly through Ca(2+) channel-independent pathway. In order to clarify proarrhythmic risk, 30 mg/kg, i.v., of azithromycin was examined with the chronic atrioventricular block dogs (n = 4). Azithromycin neither induced torsade de pointes nor affected beat-to-beat variability of repolarization. Thus, azithromycin can be considered to lack proarrhythmic potential, but caution has to be paid on its use for patients with left ventricular dysfunction.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-Nishi, Ota-ku, Tokyo, 143-8540, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yudai
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Izumi-Nakaseko
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ando
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Junichi
authors.initials: J
authors.lastname: Yamazaki
authors.forename: Takanori
authors.initials: T
authors.lastname: Ikeda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000633:toxicity; D017963:Azithromycin / Q000494:pharmacology* / Q000633:toxicity; D004285:Dogs; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D016171:Torsades de Pointes / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin