Morganroth J, Hunt T, Dorr M B, Magner D, Talbot G H
Premier Research Worldwide and University of Pennsylvania School of Medicine, Philadelphia 19103, USA.
Clin Ther. 1999 Sep;21(9):1514-24. doi: 10.1016/s0149-2918(00)80006-5.
This double-masked, randomized, placebo-controlled study was conducted to assess the effect of concomitant administration of terfenadine and sparfloxacin on the electrocardiographic (ECG) QT(c) interval in healthy volunteers, before the removal of terfenadine from the market. Eighty-eight men (aged 18 to 49 years, weighing 60.0 to 98.6 kg) with no clinically relevant ECG abnormalities received placebo, sparfloxacin (400 mg on day 1, 200 mg daily on days 2-4), terfenadine (60 mg BID), or the combination of sparfloxacin and terfenadine. After each dose, serial blood samples and ECG measurements were collected to determine sparfloxacin pharmacokinetic and pharmacodynamic variables. The area under the concentration-time curve and maximum concentration for sparfloxacin were approximately 16% less on day 4 compared with day 1, reflecting the higher plasma level after the 400-mg loading dose compared with that after the maintenance dose of 200 mg daily. Concomitant administration of terfenadine had no effect on these pharmacokinetic variables. When compared with the placebo-adjusted increases in QTc interval in the sparfloxacin (19 milliseconds on day 1 and 14 milliseconds on day 4) and terfenadine (2 milliseconds on day 1 and 7 milliseconds on day 4) treatment groups, the placebo-adjusted increases in QTc interval in the volunteers treated with the combination of sparfloxacin and terfenadine (18 milliseconds on day 1 and 22 milliseconds on day 4) were considered to be additive (no statistically significant interaction). Thus there are no apparent pharmacokinetic or dynamic QTc interactions between terfenadine and sparfloxacin. However, sparfloxacin should be administered with caution to patients receiving concomitant medications known to prolong the QTc interval.
这项双盲、随机、安慰剂对照研究旨在评估在特非那定退市前，健康志愿者同时服用特非那定和司帕沙星对心电图（ECG）QT（c）间期的影响。88名无临床相关心电图异常的男性（年龄18至49岁，体重60.0至98.6千克）接受了安慰剂、司帕沙星（第1天400毫克，第2至4天每天200毫克）、特非那定（每日两次，每次60毫克）或司帕沙星与特非那定的组合治疗。每次给药后，采集系列血样并进行心电图测量，以确定司帕沙星的药代动力学和药效学变量。与第1天相比，第4天时司帕沙星的浓度-时间曲线下面积和最大浓度约低16%，这反映出与每日200毫克维持剂量相比，400毫克负荷剂量后血浆水平更高。同时服用特非那定对这些药代动力学变量无影响。与司帕沙星（第1天19毫秒，第4天14毫秒）和特非那定（第1天2毫秒，第4天7毫秒）治疗组中经安慰剂校正后的QTc间期增加相比，司帕沙星与特非那定联合治疗的志愿者经安慰剂校正后的QTc间期增加（第1天18毫秒，第4天22毫秒）被认为是相加的（无统计学显著相互作用）。因此，特非那定和司帕沙星之间没有明显的药代动力学或动态QTc相互作用。然而，对于正在接受已知可延长QTc间期的伴随药物治疗的患者，应谨慎使用司帕沙星。
