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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 E\n                    <jats:sub>max<\/jats:sub>\n                    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\n                    <jats:italic>Anopheles dirus<\/jats:italic>\n                    and\n                    <jats:italic>An. minimus<\/jats:italic>\n                    . 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.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-58918-9","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T16:35:08Z","timestamp":1784392508000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A dynamic pharmacometric framework defining the relationship between ivermectin exposure and mosquito lethality"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5322-912X","authenticated-orcid":false,"given":"Richard M.","family":"Hoglund","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C.","family":"Kobylinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Podjanee","family":"Jittamala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borimas","family":"Hanboonkunupakarn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narenrit","family":"Wamaket","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patchara","family":"Sriwichai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siriporn","family":"Phasomkusolsil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P. 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