{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:39:39Z","timestamp":1786977579049,"version":"build-2736575974"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["220211"],"award-info":[{"award-number":["220211"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:p>\n                    Artemisinin\u2010based combination therapy (ACT) is the first\u2010line therapy for uncomplicated\n                    <jats:italic>falciparum<\/jats:italic>\n                    malaria, but artemisinin resistance in Asia and now sub\u2010Saharan Africa is threatening our ability to control and eliminate malaria. Triple\u2010ACTs have emerged as a viable alternative treatment to combat declining ACT efficacy due to drug\u2010resistant malaria. In this study, we developed and evaluated an optimal fixed\u2010dose regimen of artemether\u2010lumefantrine\u2010amodiaquine through population pharmacokinetic modeling and simulation. Three published population\u2010based pharmacometric models and two large cohorts of observed adult subjects and pediatric malaria patients were used to simulate pharmacokinetic profiles of different dosing strategies. Based on simulated total exposure and peak concentrations, an optimal dose regimen was developed resulting in an extension of the current 4 weight bands to a total of 5 weight bands to generate equivalent exposures in all body weight groups and minimize the fluctuation in exposure between patients. The proposed drug\u2010to\u2010drug ratio of artemether\u2010lumefantrine\u2010amodiaquine (20:120:40\u2009mg) was kept constant throughout the dosing bands in order to simplify manufacturing, implementation, and further development of a fixed\u2010dose co\u2010formulated product.\n                  <\/jats:p>","DOI":"10.1002\/cpt.3582","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T02:35:26Z","timestamp":1739414126000},"page":"1248-1253","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dose\u2010Optimization of a Novel Co\u2010Formulated Triple Combination Antimalarial Therapy: Artemether\u2010Lumefantrine\u2010Amodiaquine"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4566-4030","authenticated-orcid":false,"given":"Joel","family":"Tarning","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 Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-1978","authenticated-orcid":false,"given":"Nicholas J.","family":"White","sequence":"additional","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 Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5190-2395","authenticated-orcid":false,"given":"Arjen M.","family":"Dondorp","sequence":"additional","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 Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"e_1_2_11_1_1","unstructured":"WHO.World malaria report(2023)."},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314981"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00487-9"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00835-15"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01008-2"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30552-3"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00692-7"},{"key":"e_1_2_11_9_1","unstructured":"WHO.WHO guidelines for malaria(2021)."},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)70024-1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0301-z"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02193-17"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002579"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01140-19"},{"key":"e_1_2_11_15_1","unstructured":"CDC.National Center for Health Statistic & Centers for Disease Control and Prevention National Health and Nutrition Examination Survey (NHANES) III<https:\/\/wwwn.cdc.gov\/nchs\/nhanes\/nhanes3\/> (2010)."},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2005.09.021"},{"key":"e_1_2_11_17_1","unstructured":"Olola C. Agbenyega T. Kremsner P.G. Newton C.R. Bojang K.&Taylor T.Data for: A multicenter prospective observational study of intraleukocytic and intraerythrocytic pigment as prognostic features in African children withfalciparummalaria. V2 ed: Harvard Dataverse. 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