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

伊维菌素抗疟治疗恶性疟原虫肝期的评价

基本信息

批准号：
10001705
负责人：
John H Adams
金额：
$ 20.4万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-22 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10001705
关键词：
Address Affect Antimalarials Apoptosis Artemisinins Biological Assay Biological Availability Blood CYP3A4 gene Cell physiology Cells Chemoprophylaxis Clinical Treatment Clinical Trials Combined Modality Therapy Cryopreservation Culicidae Cytology Data Development Drug Combinations Drug Interactions Drug Kinetics Drug resistance Evaluation Exposure to Future Goals Hepatocyte Human In Vitro Individual Infection Ivermectin Liver Malaria Metabolic Metabolism Methods Modeling Molecular Parasite resistance Parasites Participant Pharmaceutical Preparations Pharmacodynamics Pharmacotherapy Phenotype Plasmodium Plasmodium berghei Plasmodium falciparum Plasmodium vivax Population Primaquine Property Resistance Sporozoites Translating Treatment Failure assay development base cell motility combat design in vivo infection rate inhibitor/antagonist malaria transmission mouse model novel tool transmission process trend vector mosquito

项目摘要

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.

项目概要/摘要伊维菌素大规模给药（MDA）被提议作为一种新型疟疾传播控制工具来杀死疟疾。蚊子载体。伊维菌素 MDA 经检查并发现可有效对抗伯氏疟原虫的传播，尚不清楚这是否会转化为人类疟疾。本研究的目的是确定伊维菌素 MDA 与其他抗疟药物治疗联合使用时是否可以有效消除恶性疟原虫传播，协助根除疟疾行动。伊维菌素的代谢物在肝脏阶段发育测定中使用代谢活跃的原代人肝细胞进行鉴定。利用这些数据作为基线，将评估药物之间的药代动力学药物相互作用伊维菌素和青蒿素为基础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阶段测定作为获得代谢物和进一步通过 LC-MS 检查它们。