Electrocardiographic Effects of a Supratherapeutic Dose of WCK 2349, a Benzoquinolizine Fluoroquinolone
摘要
The purpose of this study was to measure the electrocardiographic (ECG) effects of WCK 2349 (the L-alanine ester prodrug of levonadifloxacin) at a supratherapeutic oral dose of 2,600 mg. A total of 48 healthy volunteers were randomized to treatment with placebo, WCK 2349, or oral moxifloxacin, 400 mg, in a crossover-designed thorough QT study. A supratherapeutic mean maximum levonadifloxacin concentration (C-max) of 43.3 mu g/mL was achieved at 3.1 hours. A therapeutic dose of 1,000 mg b.i.d. in a previous study in patients resulted in a C-max of 17.8 mu g/mL. WCK 2349 exerted no significant effect on baseline- and placebo-corrected QTcF (QT interval corrected for heart rate (HR) by the Fridericia formula), QRS, or PR interval. HR was transiently accelerated by a maximum of 14.4 (95% confidence interval, 11.80-16.92) beats per minute (bpm) at 3 hours. Concentration-effect modeling predicted a mean increase of 8.0 bpm at C-max at the standard therapeutic dose. A therapeutic dose of 1,000 mg b.i.d. of WCK 2349 is not expected to cause clinically significant ECG effects, except for a possible transient increase in HR, which seems to be clinically insignificant.展开▼
机译：本研究的目的是测量WCK 2349（L-丙氨酸酯前药物的ECG）效应（Levonadifloxacin的L-丙氨酸酯前药），以2,600mg的Supratterical口服剂量。共有48名健康的志愿者随机用安慰剂，WCK 2349或口服Moxifloxacin，400毫克进行治疗，在交叉设计的彻底QT研究中。在3.1小时的3.1小时达到43.3μg/ ml的SupratTerapeutic的最大左旋酮胺浓度（C-max）。 1,000mg B.I.D的治疗剂量。在先前的患者的研究中导致C-MAX为17.8μg/ ml。 WCH 2349对基线和安慰剂校正的QTCF（QT间隔通过Fridericia公式进行了QT间隔（HR），QRS或PR间隔没有显着影响。 HR在3小时内瞬时加速最多14.4（95％置信区间，11.80-16.92），每分钟（BPM）在3小时。浓缩效应建模预测标准治疗剂量的C-MAX平均增加8.0bpm。 1,000mg B.I.D的治疗剂量。在WCK 2349中预计不会导致临床显着的心电图效应，除了人力资源可能的瞬态增加，似乎是临床上微不足道的。展开▼
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