{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:50:20Z","timestamp":1789192220217,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1132628"],"award-info":[{"award-number":["OPP1132628"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"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":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Resistance to the artemisinins and the artemisinin\u2010based combination therapy (ACT) partner drugs has developed in Southeast Asia, and artemisinin resistance has also emerged in eastern Africa. Triple ACTs (triple artemisinin\u2010based combination therapies, TACT), consisting of two partner drugs with different mechanisms of action and similar pharmacokinetic profiles, combined with an artemisinin derivative can help to delay or prevent artemisinin resistance and prolong the useful lifetime of the partner drugs. This study aims to characterize the pharmacokinetic properties of a recommended TACT, artemether\u2010lumefantrine plus amodiaquine, using data from two large clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed data from two randomized, controlled intervention trials conducted between 2015 and 2020 in one African country and two Southeast Asian countries, in which artemether\u2010lumefantrine was administered alone (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009443) or together with amodiaquine (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009442) to patients with uncomplicated\n                      <jats:italic>P<\/jats:italic>\n                      .\n                      <jats:italic>falciparum<\/jats:italic>\n                      malaria. Both studies included a sub\u2010cohort with dense pharmacokinetic sampling, combined with sparse data in the other patients. Concentration\u2013time data of artemether, dihydroartemisinin, lumefantrine, desbutyllumefantrine, amodiaquine and desethylamodiaquine were analysed using nonlinear mixed\u2010effects modelling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pharmacokinetic models were developed for all drugs and demonstrated good predictive performance and goodness\u2010of\u2010fit diagnostics. Coadministered amodiaquine was not a significant covariate on pharmacokinetic properties of artemether\u2010lumefantrine. Model\u2010predicted\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      and AUC (median [95% confidence interval, CI]) for artemether were 256 (159\u2013407) ng\/mL and 2850 (1820\u20104920) h\u00b7ng\/mL for artemether\u2010lumefantrine alone, and 230 (123\u2013391) ng\/mL and 2800 (1570\u20104570) h\u00b7ng\/mL for artemether\u2010lumefantrine\u2010amodiaquine. For dihydroartemisinin, values were 135 (54.5\u2013214) ng\/mL and 1870 (813\u20133015) h\u00b7ng\/mL for artemether\u2010lumefantrine alone, and 116 (40.8\u2013186) ng\/mL and 1580 (547\u20132680) h\u00b7ng\/mL for artemether\u2010lumefantrine\u2010amodiaquine. For lumefantrine, values were 15.2 (2.90\u201331.3) \u03bcg\/mL and 600 (275\u20131230) h\u00b7\u03bcg\/mL for artemether\u2010lumefantrine alone, and 14.1 (2.72\u201331.4) \u03bcg\/mL and 586 (269\u20131070) h\u00b7\u03bcg\/mL for artemether\u2010lumefantrine\u2010amodiaquine. Day 7 concentrations of lumefantrine were 452 (215\u20131240) and 438 (204\u20131030) \u03bcg\/mL for artemether\u2010lumefantrine alone and artemether\u2010lumefantrine\u2010amodiaquine, respectively. All geometric mean ratios (GMRs) for the drug\u2013drug interaction (DDI) effect on key pharmacokinetic parameters of artemether, dihydroartemisinin and lumefantrine\u00a0fell within the 0.80\u20131.25 range, with the majority of the corresponding 90% CI also contained within this range. This indicates no clinically relevant DDIs between artemether\u2010lumefantrine and amodiaquine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The DDI effect of amodiaquine on the pharmacokinetics of artemether\u2010lumefantrine is expected to be minimal, the based on the current analysis. However, further large\u2010scale clinical trials are needed to confirm this finding.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70301","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:14:42Z","timestamp":1759796082000},"page":"589-605","source":"Crossref","is-referenced-by-count":3,"title":["Population pharmacokinetics of artemether\u2013lumefantrine plus amodiaquine in patients with uncomplicated\n                    <i>Plasmodium falciparum<\/i>\n                    malaria"],"prefix":"10.1002","volume":"92","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 Medicine University of Oxford  Oxford 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