Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
Clin Pharmacol Ther. 2010 Jul;88(1):88-94. doi: 10.1038/clpt.2010.51. Epub 2010 May 19.
This study adds the dimension of a T-wave morphology composite score (MCS) to the QTc interval-based evaluation of drugs that affect cardiac repolarization. Electrocardiographic recordings from 62 subjects on placebo and 400 mg moxifloxacin were compared with those from 21 subjects on 160 and 320 mg D,L-sotalol. T-wave morphology changes, as assessed by DeltaMCS, are larger after 320 mg D,L-sotalol than after 160 mg D,L-sotalol; and the changes associated with 160 mg D,L-sotalol are, in turn, larger than those associated with moxifloxacin and placebo. Covariate analyses of DeltaQTc and DeltaMCS showed that changes in T-wave morphology are a significant effect of D,L-sotalol. By contrast, moxifloxacin was found to have no significant effect on T-wave morphology (DeltaMCS) at any given change in QTc. This study offers new insights into the repolarization behavior of a drug associated with low cardiac risk vs. one associated with a high risk and describes the added benefits of a T-wave MCS as a covariate to the assessment of the QTc interval.
本研究在基于 QTc 间期评估影响心脏复极的药物的基础上，增加了 T 波形态综合评分（MCS）的维度。将 62 名受试者在安慰剂和 400mg 莫西沙星下的心电图记录与 21 名受试者在 160mg 和 320mg D,L-索他洛尔下的心电图记录进行了比较。DeltaMCS 评估的 T 波形态变化在 320mg D,L-索他洛尔后比在 160mg D,L-索他洛尔后更大；而与 160mg D,L-索他洛尔相关的变化又大于与莫西沙星和安慰剂相关的变化。DeltaQTc 和 DeltaMCS 的协变量分析表明，T 波形态的变化是 D,L-索他洛尔的一个显著作用。相比之下，莫西沙星在任何给定的 QTc 变化下对 T 波形态（DeltaMCS）都没有显著影响。本研究为与低心脏风险相关的药物与高心脏风险相关的药物的复极行为提供了新的见解，并描述了 T 波 MCS 作为 QTc 间期评估的协变量的附加益处。
