PRACS Institute, Ltd, Fargo, ND 58104, USA.
Expert Opin Investig Drugs. 2009 Dec;18(12):1807-15. doi: 10.1517/13543780903443096.
To characterize the effects of a sustained-release formulation of fampridine (fampridine-SR) on QT interval in healthy subjects.
In a double-blind, double-dummy trial, healthy subjects were randomized to 5 days treatment with fampridine-SR at therapeutic (10 mg twice daily) or supratherapeutic (30 mg twice daily) doses, placebo or moxifloxacin (400 mg on treatment day 5). Digital 12-lead electrocardiograms were recorded before treatment and on day 5; blood samples determined fampridine concentrations. Central tendency analysis determined whether the upper limit of the CI for the QT (individual-corrected QT; QTcI) interval change exceeded 10 ms. Outlier analysis determined new-onset QT (corrected QT; QTc) intervals; maximum change in QTc from baseline of 30 - 60 ms and maximum change from baseline >or= 60 ms. The relationship between pharmacokinetic parameters and QTcI values is explored.
Moxifloxacin was associated with a QTcI interval increase > 5 ms at 7 time points; no increase was observed with either dose of fampridine-SR; there were no fampridine outliers. Pharmacokinetic evaluation failed to find dose-dependent cardiac effects. Fampridine was well tolerated, with a higher frequency of adverse events at the supratherapeutic dose.
This study showed that fampridine-SR at therapeutic and supratherapeutic doses was not associated with QT prolongation in healthy subjects.
描述控释型苯丙胺（苯丙胺-SR）对健康受试者 QT 间期的影响。
在一项双盲、双模拟试验中，健康受试者随机接受苯丙胺-SR 治疗（10 mg，每日 2 次；30 mg，每日 2 次）或安慰剂或莫西沙星（第 5 天 400 mg）治疗 5 天。治疗前和第 5 天记录数字 12 导联心电图；血样测定苯丙胺浓度。集中趋势分析确定 QT 间期校正（个体校正 QT；QTcI）变化上限是否超过 10 ms。离群值分析确定新出现的 QT（校正 QT；QTc）间期；从基线的 QTc 最大变化为 30-60 ms 和从基线最大变化>60 ms。探讨了药代动力学参数与 QTcI 值之间的关系。
莫西沙星与 7 个时间点的 QTcI 间隔增加>5 ms 相关；两种剂量的苯丙胺-SR 均未观察到 QTcI 间隔增加；未观察到苯丙胺离群值。药代动力学评估未发现剂量依赖性心脏效应。苯丙胺-SR 耐受性良好，高剂量组不良反应发生率较高。
本研究表明，治疗剂量和高治疗剂量的苯丙胺-SR 不会导致健康受试者 QT 间期延长。
