Electrophysiological safety of novel fluoroquinolone antibiotic agents gemifloxacin and balofloxacin

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-a-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 mu M, but gemifloxacin at 100 mu M significantly decreased total amplitude (p < 0.01). These values of gemifloxacin (30 and 100 mu M) were approximately 25- and 83-fold more than the free plasma concentration of 1.2 mu M in a single therapeutic injection in humans. For I-hERG, the IC50 value was about 300 mu M. Balofloxacin had also no significant effects on the resting membrane potential, total amplitude, action potential duration, and Vmax of phase 0 depolarization at concentrations up to 30 mu M, but balofloxacin at 100 mu M significantly (p < 0.01) prolonged action potentials at both 50% repolarization (APD(50)) and 90% repolarization (APD(90)). These values of balofloxacin (30 and 100 mu M) were approximately 6.8- and 23- fold more than the free plasma concentration of 4.4 mu M in a single therapeutic injection in humans. For IhERG, the IC50 value was 214 +/- 14 mu M. Therefore, our data suggested that in the electrophysiological aspect, gemifloxacin and balofloxacin may have no torsadogenic potenties up to 30 mu M.