{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T21:08:31Z","timestamp":1794344911509,"version":"4.9.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P01 HD059454"],"award-info":[{"award-number":["P01 HD059454"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Intermittent preventive treatment with monthly dihydroartemisinin-piperaquine (DHA-PQ) is highly effective at preventing both malaria during pregnancy and placental malaria. Piperaquine prolongs the corrected QT interval (QTc), and it is possible that repeated monthly dosing could lead to progressive QTc prolongation. Intensive characterization of the relationship between piperaquine concentration and QTc interval throughout pregnancy can inform effective, safe prevention guidelines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Data were collected from a randomized controlled trial, where pregnant Ugandan women received malaria chemoprevention with monthly DHA-PQ (120\/960\u00a0mg DHA\/PQ; n\u2005=\u2005373) or sulfadoxine-pyrimethamine (SP; 1500\/75\u00a0mg; n\u2005=\u2005375) during the second and third trimesters of pregnancy. Monthly trough piperaquine samples were collected throughout pregnancy, and pre- and postdose electrocardiograms were recorded at 20, 28, and 36 weeks\u2019 gestation in each woman. The pharmacokinetics\u2013QTc relationship for piperaquine and QTc for SP were assessed using nonlinear mixed-effects modeling.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A positive linear relationship between piperaquine concentration and Fridericia corrected QTc interval was identified. This relationship progressively decreased from a 4.42 to 3.28 to 2.13 millisecond increase per 100\u00a0ng\/mL increase in piperaquine concentration at 20, 28, and 36 weeks\u2019 gestation, respectively. Furthermore, 61% (n\u2005=\u2005183) of women had a smaller change in QTc at week 36 than week 20. Nine women given DHA-PQ had grade 3\u20134 cardiac adverse events. SP was not associated with any change in QTc.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Repeated DHA-PQ dosing did not result in increased risk of QTc prolongation and the postdose QTc intervals progressively decreased. Monthly dosing of DHA-PQ in pregnant women carries minimal risk of QTc prolongation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT02793622.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciab965","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T12:32:24Z","timestamp":1638361944000},"page":"406-415","source":"Crossref","is-referenced-by-count":12,"title":["Piperaquine-Induced QTc Prolongation Decreases With Repeated Monthly Dihydroartemisinin-Piperaquine Dosing in Pregnant Ugandan Women"],"prefix":"10.1093","volume":"75","author":[{"given":"Emma","family":"Hughes","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California San Francisco , San Francisco, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1166-1587","authenticated-orcid":false,"given":"Erika","family":"Wallender","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of California San Francisco , San Francisco, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kajubi","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Collaboration , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6305-758X","authenticated-orcid":false,"given":"Prasanna","family":"Jagannathan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University , Stanford, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teddy","family":"Ochieng","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Collaboration , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel","family":"Kakuru","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Collaboration , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moses R","family":"Kamya","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Collaboration , Kampala , Uganda"},{"name":"Department of Medicine, Makerere University College of Health Sciences , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara D","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Francisco , San Francisco, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Francisco , San Francisco, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Dorsey","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Francisco , San Francisco, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Aweeka","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of California San Francisco , San Francisco, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radojka M","family":"Savic","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California San Francisco , San Francisco, California , 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