Comparison of the cardiac effects of the antimalarials co-artemether and halofantrine in healthy participants
Comparison of the cardiac effects of the antimalarials co-artemether and halofantrine in healthy participants
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DOI：
10.4269/ajtmh.2002.66.293
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发表时间：
2002-03-01
影响因子：
3.3
通讯作者：
Sioufi, A
中科院分区：
文献类型：
--
作者：
Bindschedler, M;Lefèvre, G;Sioufi, A
复方蒿甲醚（Coartem（R），Riamet（R））是一种含有20毫克蒿甲醚和120毫克本芴醇的片剂，用于治疗恶性疟疾。本芴醇与卤泛群（Halfan（R））具有一些化学相似性，卤泛群是一种已知用于QTc延长的抗疟药。在一项随机双盲交叉研究中，在13名健康男性中比较了餐后单次口服500 mg卤泛群和80/480 mg复方蒿甲醚对QTc间期的影响。从给药前48小时至给药后48小时记录心电图（ECGc）。比较治疗前后和治疗间的最大QTc间期（QTc = QT/rootRR），拟合一般线性模型。同时测定药物血浆浓度。卤泛群后，所有参与者的QTc间期增加，平均最大增幅为28 ms。QTc间期的长度与卤泛群暴露呈正相关。复方蒿甲醚治疗后QTc间期保持不变。治疗之间的差异具有统计学显著性。总之，哈托泛群引起QTe间期显著的、血压依赖性增加。使用复方蒿甲醚时未观察到此类效应。
Co-artemether (Coartem(R), Riamet(R)) is a tablet containing 20 mg artemether and 120 mg lumefantrine for treatment of falciparum malaria. Lumefantrine has some chemical similarities to halofantrine (Halfan(R)), an antimalarial known for QTc prolongation. Effects on the QTc interval of fed single oral doses of 500 mg halofantrine and 80/480 mg co-artemether were compared in 13 healthy males in a randomized double-blind crossover study. Electrocardiograms (ECGc) were recorded from 48 hours before dosing until 48 hours thereafter. The maximum QTc interval (QTc = QT/rootRR) was compared before and after treatment and between treatments, fitting a general linear model. Drug plasma concentrations were determined concomitantly. After halofantrine, all participants showed an increase in the QTc interval; the mean maximum increase was 28 ms. The length of the QTc interval was positively correlated to halofantrine exposure. The QTc interval remained unchanged after co-artemether. The difference between treatments was statistically significant. In conclusion, hatofantrine caused a significant, exposure-dependent increase in the QTe interval. No such effect was seen with co-artemether.