{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:43:47Z","timestamp":1791434627845,"version":"4.3.3"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2018,4,26]],"date-time":"2018-04-26T00:00:00Z","timestamp":1524700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1099191"],"award-info":[{"award-number":["OPP1099191"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Sulfadoxine-pyrimethamine with amodiaquine is recommended by the World Health Organization as seasonal malaria chemoprevention for children aged 3 to 59 months in the sub-Sahel regions of Africa. Suboptimal dosing in children may lead to treatment failure and increased resistance. Pooled individual patient data from four previously published trials on the pharmacokinetics of sulfadoxine and pyrimethamine in 415 pediatric and 386 adult patients were analyzed using nonlinear mixed-effects modeling to evaluate the current dosing regimen and, if needed, to propose an optimized dosing regimen for children under 5 years of age. The population pharmacokinetics of sulfadoxine and pyrimethamine were both best described by a one-compartment disposition model with first-order absorption and elimination. Body weight, age, and nutritional status (measured as the weight-for-age Z-score) were found to be significant covariates. Allometric scaling with total body weight and the maturation of clearance in children by postgestational age improved the model fit. Underweight-for-age children were found to have 15.3% and 26.7% lower bioavailabilities of sulfadoxine and pyrimethamine, respectively, for each Z-score unit below \u22122. Under current dosing recommendations, simulation predicted that the median day 7 concentration was below the 25th percentile for a typical adult patient (50 kg) for sulfadoxine for patients in the weight bands of 8 to 9, 19 to 24, 46 to 49, and 74 to 79 kg and for pyrimethamine for patients in the weight bands of 8 to 9, 14 to 24, and 42 to 49 kg. An evidence-based dosing regimen was constructed that would achieve sulfadoxine and pyrimethamine exposures in young children and underweight-for-age young children that were similar to those currently seen in a typical adult.<\/jats:p>","DOI":"10.1128\/aac.01370-17","type":"journal-article","created":{"date-parts":[[2018,2,19]],"date-time":"2018-02-19T14:29:42Z","timestamp":1519050582000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria"],"prefix":"10.1128","volume":"62","author":[{"given":"Min\u00e9","family":"de Kock","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Worldwide Antimalarial Resistance Network (WWARN), Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4566-4030","authenticated-orcid":false,"given":"Joel","family":"Tarning","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, United Kingdom"},{"name":"Worldwide Antimalarial Resistance Network (WWARN), Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Workman","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Worldwide Antimalarial Resistance Network (WWARN), Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth N.","family":"Allen","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamadou M.","family":"Tekete","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, Bamako, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdoulaye A.","family":"Djimde","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, Bamako, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Bell","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Queen Elizabeth University Hospital, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve A.","family":"Ward","sequence":"additional","affiliation":[{"name":"Molecular and Biochemical Parasitology Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen I.","family":"Barnes","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Worldwide Antimalarial Resistance Network (WWARN), Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Denti","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Worldwide Antimalarial Resistance Network (WWARN), Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"World malaria report 2015","author":"WHO","year":"2015","unstructured":"WHO. 2015. 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