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There are no approved antiviral drugs to treat dengue infections. Ivermectin, an old anti\u2010parasitic drug, had no effect on dengue viremia, but reduced the dengue non\u2010structural protein 1 (NS1) in a clinical trial. This is potentially important, as NS1 may play a causal role in the pathogenesis of severe dengue. This study established an in\u2010host model to characterize the plasma kinetics of dengue virus and NS1 with host immunity and evaluated the effects of ivermectin, using a population pharmacokinetic\u2013pharmacodynamic (PK\u2013PD) modeling approach, based on two studies in acute dengue fever: a placebo\u2010controlled ivermectin study in 250 adult patients and an ivermectin PK\u2013PD study in 24 pediatric patients. The proposed model described adequately the observed ivermectin pharmacokinetics, viral load, and NS1 data. Bodyweight was a significant covariate on ivermectin pharmacokinetics. We found that ivermectin reduced NS1 with an EC<jats:sub>50<\/jats:sub> of 67.5\u2009\u03bcg\/mL. In silico simulations suggested that ivermectin should be dosed within 48\u2009h after fever onset, and that a daily dosage of 800\u2009\u03bcg\/kg could achieve substantial NS1 reduction. The in\u2010host dengue model is useful to assess the drug effect in antiviral drug development for dengue fever.<\/jats:p>","DOI":"10.1002\/psp4.13233","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T09:28:55Z","timestamp":1727083735000},"page":"2196-2209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["In\u2010host modeling of dengue virus and non\u2010structural protein 1 and the effects of ivermectin in patients with acute dengue fever"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-3178","authenticated-orcid":false,"given":"Junjie","family":"Ding","sequence":"first","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine Mahidol University  Bangkok Thailand"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine University of Oxford  Oxford 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