Mass administration of antimalarial drugs and ivermectin are being considered as potential accelerators of malaria elimination. The safety, tolerability, pharmacokinetics, and mosquito-lethal effects of combinations of ivermectin, dihydroartemisinin-piperaquine, and primaquine were evaluated. Coadministration of ivermectin and dihydroartemisinin-piperaquine resulted in increased ivermectin concentrations with corresponding increases in mosquito-lethal effect across all subjects. Exposure to piperaquine was also increased when coadministered with ivermectin, but electrocardiograph QT-interval prolongation was not increased. One subject had transiently impaired liver function. Ivermectin mosquito-lethal effect was greater than predicted previously against the major Southeast Asian malaria vectors. Both Anopheles dirus and Anopheles minimus mosquito mortality was increased substantially (20-fold and 35-fold increase, respectively) when feeding on volunteer blood after ivermectin administration compared with in vitro ivermectin-spiked blood. This suggests the presence of ivermectin metabolites that impart mosquito-lethal effects. Further studies of this combined approach to accelerate malaria elimination are warranted.

中文翻译：

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伊维菌素联合双氢青蒿素-哌喹和伯氨喹对泰国健康成人受试者的安全性、药代动力学和蚊子致死作用。

抗疟药和伊维菌素的大规模给药被认为是消除疟疾的潜在加速器。评估了伊维菌素、双氢青蒿素-哌喹和伯氨喹联合用药的安全性、耐受性、药代动力学和蚊子致死作用。伊维菌素和双氢青蒿素-哌喹的共同给药导致伊维菌素浓度增加，所有受试者的蚊子致死效应相应增加。与伊维菌素合用时，哌喹的暴露量也增加，但心电图 QT 间期延长并未增加。一名受试者的肝功能暂时受损。伊维菌素对蚊子的致死作用比之前预测的对东南亚主要疟疾传播媒介的影响要大。与体外添加伊维菌素的血液相比，在施用伊维菌素后以志愿者血液为食时，大按蚊和小按蚊蚊子的死亡率均显着增加（分别增加 20 倍和 35 倍）。这表明伊维菌素代谢物的存在会导致蚊子致死作用。有必要对这种加速消除疟疾的联合方法进行进一步研究。