Azithromycin Can Prolong QT Interval and Suppress Ventricular Contraction, but Will Not Induce Torsade de Pointes

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• 作者：Hiroshi Ohara ; Yuji Nakamura ; Yudai Watanabe ; Xin Cao…
• 关键词：Azithromycin ; Ventricular contraction ; QT prolongation ; I Kr ; Torsade de pointes ; Atrioventricular block
• 刊名：Cardiovascular Toxicology
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：15
• 期：3
• 页码：232-240
• 全文大小：1,003 KB
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• 作者单位：Hiroshi Ohara (1) (2)
  Yuji Nakamura (1)
  Yudai Watanabe (1)
  Xin Cao (1)
  Yukiko Yamazaki (1) (2)
  Hiroko Izumi-Nakaseko (1)
  Kentaro Ando (1)
  Hiroshi Yamazaki (3)
  Junichi Yamazaki (2)
  Takanori Ikeda (2)
  Atsushi Sugiyama (1)
  
  1. Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-Nishi, Ota-ku, Tokyo, 143-8540, Japan
  2. Division of Cardiovascular Medicine, Department of Internal Medicine, Faculty of Medicine, Toho University, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan
  3. Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, 3-3165 Higashi-tamagawa Gakuen, Machida, Tokyo, 194-8543, Japan
  
• 刊物主题：Pharmacology/Toxicology; Cardiology;
• 出版者：Springer US
• ISSN：1559-0259

文摘

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 Ca2+ 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.