{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:06:26Z","timestamp":1787234786442,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T00:00:00Z","timestamp":1725321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Artemisinin\u2010based combination therapy (ACT) is the first\u2010line recommended treatment for uncomplicated malaria. Pharmacokinetic (PK) properties in pregnant women are often based on small studies and need to be confirmed and validated in larger pregnant patient populations. This study aimed to evaluate the PK properties of amodiaquine and its active metabolite, desethylamodiaquine, and piperaquine in women in their second and third trimester of pregnancy with uncomplicated <jats:italic>P. falciparum<\/jats:italic> infections. Eligible pregnant women received either artesunate\u2010amodiaquine (200\/540\u2009mg daily, <jats:italic>n<\/jats:italic>\u2009=\u2009771) or dihydroartemisinin\u2010piperaquine (40\/960\u2009mg daily, <jats:italic>n<\/jats:italic>\u2009=\u2009755) for 3\u2009days (NCT00852423). Population PK properties were evaluated using nonlinear mixed\u2010effects modeling, and effect of gestational age and trimester was evaluated as covariates. 1071 amodiaquine and 1087 desethylamodiaquine plasma concentrations, and 976 piperaquine plasma concentrations, were included in the population PK analysis. Amodiaquine concentrations were described accurately with a one\u2010compartment disposition model followed by a two\u2010compartment disposition model of desethylamodiaquine. The relative bioavailability of amodiaquine increased with gestational age (1.25% per week). The predicted exposure to desethylamodiaquine was 2.8%\u201332.2% higher in pregnant women than that reported in non\u2010pregnant women, while day 7 concentrations were comparable. Piperaquine concentrations were adequately described by a three\u2010compartment disposition model. Neither gestational age nor trimester had significant impact on the PK of piperaquine. The predicted exposure and day 7 concentrations of piperaquine were similar to that reported in non\u2010pregnant women. In conclusion, the exposure to desethylamodiaquine and piperaquine was similar to that in non\u2010pregnant women. Dose adjustment is not warranted for women in their second and their trimester of pregnancy.<\/jats:p>","DOI":"10.1002\/psp4.13211","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T05:39:26Z","timestamp":1725428366000},"page":"1893-1903","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Population pharmacokinetics of amodiaquine and piperaquine in African pregnant women with uncomplicated <i>Plasmodium falciparum<\/i> infections"],"prefix":"10.1002","volume":"13","author":[{"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 Clinical Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard 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