Last Updated: 03/11/2017

Ivermectin active metabolite identification, purification and pharmacokinetics

Objectives

The overall goal of this project is to advance the understanding of the pharmacology of ivermectin and to enhance the treatment of malaria.

The specific objectives are to:

  1. identify and characterize ivermectin metabolite production in vitro and in vivo,
  2. determine which metabolites impart mosquito-lethal effect in the major Greater Mekong Subregion Anopheles vectors,
  3. assess parent compound and metabolite activity and pharmacokinetics to characterize the duration of mosquito-lethal effects of oral ivermectin in a detailed clinical trial, and
  4. investigate whether ivermectin alters drug sensitivity in artemisinin-resistant P. falciparum field isolates.  
Principal Institution

University of Oxford

Principal Investigators / Focal Persons

Joel Tarning

Rationale and Abstract

Ivermectin is lethal to Anopheles mosquitoes at concentrations safe to administer to people during mass drug administrations. However, mosquito survival from field MDA, laboratory, and clinical trial assays, and pharmacokinetic results do not always correlate with laboratory assays with ivermectin compound under predicting mosquito-lethal effect observed in field MDAs and clinical trials. This suggests that there may be ivermectin metabolites with a mosquito-lethal effect that extend the window of efficacy beyond that predicted by parent compound pharmacokinetics.

Date

Nov 2017 — Feb 2022

Total Project Funding

$890,159

Funding Details
Project Site

Thailand

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