Evaluation of ivermectin as an antimalarial therapy against P. falciparum liver stage

项目摘要/摘要 伊维菌素集体给药(Mda)是一种新型的疟疾传播控制工具。 蚊子媒介。其中伊维菌素丙二醛已被检查并发现对 伯氏疟原虫的传播，目前尚不清楚这是否会转化为人类疟疾。这项研究的目的是 确定伊维菌素丙二醛与其他抗疟疾药物联合治疗时是否对 消除恶性疟原虫传播，协助根除疟疾倡议。伊维菌素代谢物将是 在肝期发育试验中使用具有代谢活性的原代人肝细胞进行鉴定。 利用这些数据作为基线，药代动力学药物-药物相互作用将在 基于伊维菌素和青蒿素的联合疗法将在未来的临床试验中进行分析。这些方法 还将利用原代人肝细胞肝期试验作为获得代谢物的一种方式，并进一步 通过LC-MS对它们进行检测。

Project Summary/Abstract Ivermectin mass drug administration (MDA) is proposed as a novel malaria transmission control tool to kill the mosquito vectors. Where Ivermectin MDA has been examined and found to be effective against the transmission of Plasmodium berghei, it unclear if this translates to human malaria. The objective of this study is to determine if Ivermectin MDA, when combined with other antimalarial drug treatments, could be effective in eliminating P. falciparum transmission, aiding in the malaria eradication initiative. Ivermectin metabolites will be identified using metabolically-active primary human hepatocytes in the liver stage development assay. Leveraging these data as the baseline, pharmacokinetic drug-drug interactions will be evaluated between ivermectin and artemisinin-based combination therapies to be analyzed in future clinical trials. These methods will also utilize the primary human hepatocyte liver stage assay as a way to obtain metabolites and further examine them via LC-MS.