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

• 批准号: 10170295
• 负责人: John H Adams
• 金额: $ 15.73万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-22 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170295
• 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

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.

项目总结/摘要 伊维菌素大规模给药（MDA）被认为是一种新的疟疾传播控制工具， 蚊媒。当伊维菌素MDA已被检查并发现有效对抗 伯氏疟原虫的传播，目前还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与其他抗疟药物联合治疗是否有效， 消除恶性疟原虫的传播，帮助消灭疟疾倡议。伊维菌素代谢物将 在肝脏阶段发育试验中使用代谢活性原代人肝细胞鉴定。 利用这些数据作为基线，将在以下两组之间评价药代动力学药物相互作用： 伊维菌素和青蒿素联合疗法将在今后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脏阶段试验作为获得代谢物的方法， 通过LC-MS检查它们。

项目成果

Identification of the metabolites of ivermectin in humans.

• DOI: 10.1002/prp2.712
• 发表时间: 2021-03
• 期刊: Pharmacology research & perspectives
• 影响因子: 2.6
• 作者: Tipthara P;Kobylinski KC;Godejohann M;Hanboonkunupakarn B;Roth A;Adams JH;White NJ;Jittamala P;Day NPJ;Tarning J
• 通讯作者: Tarning J