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Abstract：
Women are associated with longer electrocardiographic QT intervals and increased proarrhythmic risks of QT-prolonging drugs. The purpose of this study was to characterize the differences in cardiac electrophysiology between moxifloxacin and levofloxacin in men and women and to assess the balance of inward and outward currents through the analysis of QT subintervals. Data from 2 TQT studies were used to investigate the impact of moxifloxacin (400 mg) and levofloxacin (1000 and 1500 mg) on QT subintervals using algorithms for measurement of J-Tpeak and Tpeak -Tend intervals. Concentration-effect analyses were performed to establish potential relationships between the ECG effects and the concentrations of the 2 fluoroquinolones. Moxifloxacin was shown to be a more potent prolonger of QT interval corrected by Fredericia (QTcF) and had a pronounced effect on J-Tpeak c. Levofloxacin had little effect on J-Tpeak c. For moxifloxacin, the concentration-effect modeling showed a greater effect for women on QTcF and J-Tpeak c, whereas for levofloxacin the inverse was true: women had smaller QTcF and J-Tpeak c effects. The different patterns in repolarization after administration of both drugs suggested a sex difference, which may be related to the combined IKs and IKr inhibitory properties of moxifloxacin versus IKr suppression only of levofloxacin. The equipotent inhibition of IKs and IKr appears to affect women more than men. Sex hormones are known to influence cardiac ion channel expression and differences in QT duration. Differences in IKr and IKs balances, influenced by sex hormones, may explain the results. These results support the impact of sex differences on the cardiac safety assessment of drugs.
摘要：
女性与更长的心电图QT间期和QT延长药物的心律失常风险增加有关。这项研究的目的是表征男性和女性莫西沙星和左氧氟沙星之间的心脏电生理差异，并通过对QT子间隔的分析来评估内向电流和外向电流的平衡。使用来自2项TQT研究的数据来研究莫西沙星（400mg）和左氧氟沙星（1000和1500mg）对QT子间隔的影响，使用用于测量J-Tpeak和Tpeak-Tend间隔的算法。进行浓度效应分析以建立ECG效应与2种氟喹诺酮类药物浓度之间的潜在关系。莫西沙星被证明是由Fredericia（QTcF）校正的QT间期更有效的延长，并且对J-Tpeakc有明显的影响。左氧氟沙星对J-Tpeakc几乎没有影响。对于莫西沙星，浓度效应模型显示女性对QTcF和J-Tpeakc的影响更大，而对于左氧氟沙星，则相反：女性的QTcF和J-Tpeakc效应较小。两种药物给药后复极化的不同模式表明了性别差异，这可能与莫西沙星的IKs和IKr抑制特性以及仅左氧氟沙星的IKr抑制特性有关。IKs和IKr的等效抑制似乎对女性的影响大于男性。已知性激素会影响心脏离子通道的表达和QT持续时间的差异。IKr和IKs余额的差异，受性激素的影响，可以解释结果。这些结果支持性别差异对药物心脏安全性评估的影响。
