{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:08:49Z","timestamp":1785424129262,"version":"3.56.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100002322","name":"CAPES","doi-asserted-by":"crossref","award":["1"],"award-info":[{"award-number":["1"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["422821\/2025-0"],"award-info":[{"award-number":["422821\/2025-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["440227\/2022-4"],"award-info":[{"award-number":["440227\/2022-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      A combination between artesunate (AS) and mefloquine (MQ) (ASMQ) is widely employed for the treatment of uncomplicated\n                      <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                      . Despite this, pharmacokinetic (PK) and underlying relationship between PK and pharmacodynamic (PD) are relatively less known than other standard combination therapy. This study aimed to develop population PK models for ASMQ combination therapy in\n                      <jats:italic toggle=\"yes\">P. berghei<\/jats:italic>\n                      -infected mice and to further characterize the PK\/PD relationships by assessing the impact of different dosing strategies through a model-based simulation. Plasma PK was assessed in infected mice receiving a single oral dose of 100\u202fmg\/kg AS and 55\u202fmg\/kg MQ after allometric scaling to mice dose. A two-compartment model with first-order absorption and linear elimination best described both drugs' concentration-time profiles. PK\/PD modeling, performed using a turnover model in MonolixSuite 2024R1, revealed IC\u2085\u2080 values of 10.93\u202fnM for artesunate and 29.1\u202fnM for mefloquine, indicating strong potency. Simulations demonstrated that both ASMQ dosing regimens (100\/55 and 25\/55 mg\/kg) resulted in comparable parasitemia suppression (~85%) and sustained efficacy. In contrast, AS monotherapy exhibited a rapid initial parasite clearance, but this was followed by a parasite recrudescence. These findings underscore the value of combination therapy and highlight the utility of integrated PK\/PD modeling to inform antimalarial treatment optimization in preclinical studies and support translational application.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01717-25","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:00:31Z","timestamp":1770904831000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic and pharmacodynamic modeling of anti-plasmodial drugs mefloquine plus artesunate: insights on translational application"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9359-8527","authenticated-orcid":true,"given":"Sabiha R.","family":"Mim","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02y3ad647","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida","place":["Orlando, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valdeene","family":"Vieira Santos","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03k3p7647","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmacy Graduate Program, College of Pharmacy, Federal University of Bahia","place":["Salvador, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laiz Campos","family":"Pereira","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03k3p7647","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmacy Graduate Program, College of Pharmacy, Federal University of Bahia","place":["Salvador, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiana","family":"Pica","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02y3ad647","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida","place":["Orlando, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline Lorena Louren\u00e7o dos Santos","family":"Miranda","sequence":"additional","affiliation":[{"name":"Fiocruz, Instituto Gon\u00e7alo Moniz","place":["Salvador, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helenita Costa","family":"Quadros","sequence":"additional","affiliation":[{"name":"Department of Technology and Social Sciences, State University of Bahia","place":["Juazeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3323-4404","authenticated-orcid":true,"given":"Diogo Rodrigo Magalhaes","family":"Moreira","sequence":"additional","affiliation":[{"name":"Fiocruz, Instituto Gon\u00e7alo Moniz","place":["Salvador, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3625-0186","authenticated-orcid":true,"given":"Francine Johansson","family":"Azeredo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02y3ad647","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida","place":["Orlando, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"WHO. 2024. On Vancouver style: World Health Organization. World malaria report 2024. Geneva World Health Organization. https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2024."},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-023-05755-8"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14474"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/trstmh\/trw077"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(95)90094-2"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.2.341"},{"key":"e_1_3_4_9_2","volume-title":"Guidelines for the treatment of malaria","author":"World Health Organization","year":"2015","unstructured":"World Health Organization. 2015. Guidelines for the treatment of malaria. 3rd ed. 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