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The Action of a Novel Fluoroquinolone Antibiotic Agent Antofloxacin Hydrochloride on Human‐Ether‐ à‐go‐go‐ Related Gene Potassium Channel
Author(s) -
Guo Jia,
Han ShengNa,
Liu JinXu,
Zhang XiangMei,
Hu ZhenSheng,
Shi Jie,
Zhang LiRong,
Zhao ZhongZhong,
Zhang Zhao
Publication year - 2010
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2010.00550.x
Subject(s) - herg , sparfloxacin , pharmacology , chemistry , potassium channel , potency , patch clamp , ic50 , levofloxacin , potassium channel blocker , hydrochloride , hek 293 cells , cardiac action potential , biochemistry , biophysics , repolarization , in vitro , ofloxacin , antibiotics , electrophysiology , medicine , biology , gene , receptor , ciprofloxacin
The administration of certain fluoroquinolone antibacterials has recently been linked to QT interval prolongation, raising the clinical concerns over the cardiotoxicity of these agents. In this study, the effects of a novel fluoroquinolone, antofloxacin hydrochloride (AX) on human‐ ether‐à‐go‐go ‐related gene (HERG) encoding potassium channels and the biophysical mechanisms of drug action were performed with whole‐cell patch‐clamp technique in transiently transfected HEK293 cells. The administration of AX caused voltage‐ and time‐dependent inhibition of HERG K + current ( I HERG/MiRP1 ) in a concentration‐dependent manner but did not markedly modify the properties of channel kinetics, including activation, inactivation, deactivation and recovery from inactivation as well. In comparison with sparfloxacin (SPX), levofloxacin lactate (LVFX), the potency of AX to inhibit HERG tail currents was the least one, with an IC 50 value of 460.37 μM. By contrast, SPX was the most potent compound, displaying an IC 50 value of 2.69 μM whereas LVFX showed modest potency, with an IC 50 value of 43.86 μM, respectively. Taken together, our data suggest that AX only causes a minor reduction of I HERG/MiRP1 at the estimated free plasma level.