单次口服给药后硫利达嗪和甲砜达嗪对健康成年人QT间期影响的比较。

Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.

作者信息

Salih I S M, Thanacoody R H K, McKay G A, Thomas S H L

机构信息

School of Clinical and Laboratory Sciences, University of Newcastle, Newcastle-upon-Tyne, Newcastle, UK.

出版信息

Clin Pharmacol Ther. 2007 Nov;82(5):548-54. doi: 10.1038/sj.clpt.6100194. Epub 2007 Apr 4.

DOI:10.1038/sj.clpt.6100194

PMID:17410120

Abstract

We compared the effects of single doses of thioridazine and mesoridazine on the heart rate-corrected QT (QTc) interval in healthy adult volunteers. QTc intervals and plasma concentrations of thioridazine, mesoridazine, and metabolites were measured after single oral doses of thioridazine hydrochloride 50 mg, mesoridazine besylate 50 mg, or placebo in a double-blind, crossover study. Mean maximum increases in the QTc interval following thioridazine (37.3+/-4.1 ms, P=0.023) and mesoridazine (46.6+/-7.4 ms, P=0.021) were similar and significantly greater than following placebo (12.9+/-8.1 ms). The area under the effect-time curve over 8 h following drug administration was similar between the two drugs (129.3+/-22.1 vs 148.3+/-43.0 ms h). In conclusion, thioridazine and mesoridazine are associated with similar effects on the QTc interval.

摘要

我们比较了单次剂量的硫利达嗪和甲砜哒嗪对健康成年志愿者心率校正QT（QTc）间期的影响。在一项双盲、交叉研究中，给予健康成年志愿者单次口服50mg盐酸硫利达嗪、50mg甲磺酸甲砜哒嗪或安慰剂后，测量QTc间期以及硫利达嗪、甲砜哒嗪及其代谢产物的血浆浓度。硫利达嗪（37.3±4.1ms，P=0.023）和甲砜哒嗪（46.6±7.4ms，P=0.021）给药后QTc间期的平均最大增加相似，且显著大于安慰剂组（12.9±8.1ms）。给药后8小时内，两种药物的效应-时间曲线下面积相似（129.3±22.1对148.3±43.0ms·h）。总之，硫利达嗪和甲砜哒嗪对QTc间期的影响相似。