{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T22:56:00Z","timestamp":1775170560475,"version":"3.50.1"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T00:00:00Z","timestamp":1492992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T00:00:00Z","timestamp":1493596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"European Research Council","award":["ERC-2014-StG 639776"],"award-info":[{"award-number":["ERC-2014-StG 639776"]}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["AFIRM OPP1034789"],"award-info":[{"award-number":["AFIRM OPP1034789"]}],"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":[[2017,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Low-dose primaquine is recommended to prevent\n            <jats:named-content content-type=\"genus-species\">Plasmodium falciparum<\/jats:named-content>\n            malaria transmission in areas threatened by artemisinin resistance and areas aiming for malaria elimination. Community treatment campaigns with artemisinin-based combination therapy in combination with the gametocytocidal primaquine dose target all age groups, but no studies thus far have assessed the pharmacokinetics of this gametocytocidal drug in African children. We recruited 40 children participating in a primaquine efficacy trial in Burkina Faso to study primaquine pharmacokinetics. These children received artemether-lumefantrine and either a 0.25- or a 0.40-mg\/kg primaquine dose. Seven blood samples were collected from each participant for primaquine and carboxy-primaquine plasma levels determinations: one sample was collected before primaquine administration and six after primaquine administration according to partially overlapping sampling schedules. Physiological population pharmacokinetic modeling was used to assess the impact of weight, age, and\n            <jats:italic>CYP2D6<\/jats:italic>\n            genotype on primaquine and carboxy-primaquine pharmacokinetics. Despite linear weight normalized dosing, the areas under the plasma concentration-time curves and the peak concentrations for both primaquine and carboxy-primaquine increased with age and body weight. Children who were CYP2D6 poor metabolizers had higher levels of the parent compound, indicating a lower primaquine CYP2D6-mediated metabolism. Our data indicate that primaquine and carboxy-primaquine pharmacokinetics are influenced by age, weight, and\n            <jats:italic>CYP2D6<\/jats:italic>\n            genotype and suggest that dosing strategies may have to be reconsidered to maximize the transmission-blocking properties of primaquine. (This study has been registered at ClinicalTrials.gov under registration no. NCT01935882.)\n          <\/jats:p>","DOI":"10.1128\/aac.02590-16","type":"journal-article","created":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T00:42:27Z","timestamp":1489452147000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Age, Weight, and\n            <i>CYP2D6<\/i>\n            Genotype Are Major Determinants of Primaquine Pharmacokinetics in African Children"],"prefix":"10.1128","volume":"61","author":[{"given":"Bronner P.","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmi","family":"Pett","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfred B.","family":"Tiono","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daryl","family":"Murry","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sodiomon B.","family":"Sirima","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikko","family":"Niemi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teun","family":"Bousema","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Drakeley","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob","family":"ter Heine","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Single dose primaquine as a gametocytocide in Plasmodium falciparum malaria","author":"World Health Organization","year":"2012","unstructured":"World Health Organization. 2012. 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