Key result
Antofloxacin exhibits substantially weaker HERG current inhibition than sparfloxacin and levofloxacin in preclinical models.
Why the study?
Certain fluoroquinolone antibacterials have been linked to QT interval prolongation, raising concerns about their cardiotoxicity.
Does antofloxacin hydrochloride inhibit HERG potassium channels compared to other fluoroquinolones in HEK293 cells?
Does antofloxacin hydrochloride inhibit HERG potassium channels compared to other fluoroquinolones in HEK293 cells?
Absolute Event Rate: 460.37% vs 2.69%
Antofloxacin hydrochloride exhibits significantly lower potency in inhibiting HERG potassium channels compared to sparfloxacin and levofloxacin, suggesting a lower risk of drug-induced QT interval prolongation.
May indicate lower QT risk with antofloxacin; leaves open clinical translation pending human studies.
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 microM. By contrast, SPX was the most potent compound, displaying an IC(50) value of 2.69 microM whereas LVFX showed modest potency, with an IC(50) value of 43.86 microM, respectively. Taken together, our data suggest that AX only causes a minor reduction of I(HERG/MiRP1) at the estimated free plasma level.
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Guo et al. (2010) studied Cardiotoxicity (QT interval prolongation). Antofloxacin hydrochloride (AX) vs. Sparfloxacin (SPX) and levofloxacin lactate (LVFX) was evaluated on Inhibition of HERG tail currents (IC50). Antofloxacin hydrochloride exhibited the least potency in inhibiting HERG tail currents with an IC50 of 460.37 microM, compared to sparfloxacin (2.69 microM) and levofloxacin (43.86 microM).
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