Electrophysiological Safety of Novel Fluoroquinolone Antibiotic Agents Gemifloxacin and Balofloxacin

Abstract

Some fluoroquinolones have been reported to induce QT interval prolongation associated with the onset of torsades de pointes (TdP), resulting in a life-threatening ventricular arrhythmia. We investigated the cardiac electrophysiological effects of two new fluoroquinolones, gemifloxacin and balofloxacin, by using conventional microelectrode recording techniques in isolated rabbit Purkinje fiber and whole-cell patch-clamp techniques in human ether-á-go-go related gene (hERG)-transient transfected CHO cells. Gemifloxacin had no significant effects on the resting membrane potential, total amplitude, action potential, and V_max of phase 0 depolarization at concentrations up to 30 μM, but gemifloxacin at 100 μM significantly decreased total amplitude (p < 0.01). These values of gemifloxacin (30 and 100 μM) were approximately 25- and 83-fold more than the free plasma concentration of 1.2 μM in a single therapeutic injection in humans. For I_hERG, the IC₅₀ value was about 300 μM. Balofloxacin had also no significant effects on the resting membrane potential, total amplitude, action potential duration, and V_max of phase 0 depolarization at concentrations up to 30 μM, but balofloxacin at 100 μM significantly (p < 0.01) prolonged action potentials at both 50% repolarization (APD₅₀) and 90% repolarization (APD₉₀). These values of balofloxacin (30 and 100 μM) were approximately 6.8- and 23-fold more than the free plasma concentration of 4.4 μM in a single therapeutic injection in humans. For I_hERG, the IC₅₀ value was 214 ± 14 μM. Therefore, our data suggested that in the electrophysiological aspect, gemifloxacin and balofloxacin may have no torsadogenic potenties up to 30 μM.

Key Words: :

• Action potential
• Fluoroquinolones
• hERG
• QT interval prolongation