A dynamic pharmacometric framework defining the relationship between ivermectin exposure and mosquito lethality
- 1Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University
- 2Department of Entomology, Armed Forces Research Institute of Medical Sciences
- 3Department of Medical Entomology, Faculty of Tropical Medicine, Mahidol University
Abstract
Ivermectin is used in the treatment of several neglected tropical diseases. Studies have shown that it effectively kills anopheline mosquitoes. However, the relationship between the pharmacokinetic properties and mosquito-lethal effects have not been described quantitatively. Pharmacokinetic properties and mosquito-lethal effects associated with a single oral administration of ivermectin were evaluated in two healthy volunteer trials in Thailand. All data were pooled and analysed using nonlinear mixed-effect modelling. Ivermectin and metabolites were described by a parent-metabolite model. When co-administered with dihydroartemisinin-piperaquine, a reduced elimination clearance (41%) and a slower absorption (32%) of ivermectin was identified, resulting in higher exposures. Different peripheral volume of distributions of ivermectin in men and women were also observed (75% higher in females). Individual pharmacokinetic profiles were incorporated in a sigmoidal Emax model, which were used to quantify the relationship between ivermectin exposure and mosquito-lethal effects. The integrated models described successfully the observed mortality of both Anopheles dirus and An. minimus. The final models were used to illustrate the potential impact on vector-control associated with ivermectin administration. In conclusion, ivermectin and its metabolites showed effective mosquito-lethal effects. The developed pharmacometric framework could be a useful tool in the evaluation of ivermectin as a potential vector-control agent in malaria elimination campaigns.
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BibTeX
@article{hoglund2026dynamic,
title = {{A dynamic pharmacometric framework defining the relationship between ivermectin exposure and mosquito lethality}},
author = {Richard M. Hoglund and Kevin C. Kobylinski and Podjanee Jittamala and Borimas Hanboonkunupakarn and Narenrit Wamaket and Patchara Sriwichai and Siriporn Phasomkusolsil and Nicholas J. White and Nicholas P. J. Day and Joel Tarning},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-58918-9},
url = {https://doi.org/10.1038/s41598-026-58918-9},
note = {CC BY},
}
RIS
TY - JOUR
TI - A dynamic pharmacometric framework defining the relationship between ivermectin exposure and mosquito lethality
AU - Richard M. Hoglund
AU - Kevin C. Kobylinski
AU - Podjanee Jittamala
AU - Borimas Hanboonkunupakarn
AU - Narenrit Wamaket
AU - Patchara Sriwichai
AU - Siriporn Phasomkusolsil
AU - Nicholas J. White
AU - Nicholas P. J. Day
AU - Joel Tarning
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-58918-9
UR - https://doi.org/10.1038/s41598-026-58918-9
AB - Ivermectin is used in the treatment of several neglected tropical diseases. Studies have shown that it effectively kills anopheline mosquitoes. However, the relationship between the pharmacokinetic properties and mosquito-lethal effects have not been described quantitatively. Pharmacokinetic properties and mosquito-lethal effects associated with a single oral administration of ivermectin were evaluated in two healthy volunteer trials in Thailand. All data were pooled and analysed using nonlinear mixed-effect modelling. Ivermectin and metabolites were described by a parent-metabolite model. When co-administered with dihydroartemisinin-piperaquine, a reduced elimination clearance (41%) and a slower absorption (32%) of ivermectin was identified, resulting in higher exposures. Different peripheral volume of distributions of ivermectin in men and women were also observed (75% higher in females). Individual pharmacokinetic profiles were incorporated in a sigmoidal Emax model, which were used to quantify the relationship between ivermectin exposure and mosquito-lethal effects. The integrated models described successfully the observed mortality of both Anopheles dirus and An. minimus. The final models were used to illustrate the potential impact on vector-control associated with ivermectin administration. In conclusion, ivermectin and its metabolites showed effective mosquito-lethal effects. The developed pharmacometric framework could be a useful tool in the evaluation of ivermectin as a potential vector-control agent in malaria elimination campaigns.
SN - 2045-2322
ER -