Thanaporn WattanakulBernhards OgutuAbdunoor M. KabanywanyiKwaku Poku AsanteAbraham OduroAlex AdjeiAli SieEsperanca SeveneEusebio MacEteGuillaume CompaoreInnocent ValeaIsaac OseiMarkus WinterbergMargaret GyapongMartin AdjuikSalim AbdullaSeth Owusu-AgyeiNicholas J. WhiteNicholas P.J. DayHalidou TintoRita BaidenFred BinkaJoel TarningUniversity of Health and Allied Sciences, GhanaCentre de Recherche en Sante de NounaNavrongo Health Research CenterKintampo Health Research CentreIfakara Health InstituteKenya Medical Research InstituteMahidol UniversityNuffield Department of MedicineClinical Research Unit of Nanoro (IRSS-URCN)Dodowa Health Research CentreWorldWide Antimalarial Resistance NetworkCentro de Investigação em Saúde de ManhiçaINDEPTH Network2020-08-252020-08-252020-07-01Antimicrobial Agents and Chemotherapy. Vol.64, No.7 (2020)10986596006648042-s2.0-85087095233https://repository.li.mahidol.ac.th/handle/20.500.14594/58113Copyright © 2020 Wattanakul et al. Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicenter trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90-ms mean QTc prolongation per 100-ng/ml increase in piperaquine concentration. The effect of piperaquine on absolute QTc interval estimated a mean maximum QTc interval of 456 ms (50% effective concentration of 209 ng/ml). Simulations from the pharmacokinetic-pharmacodynamic models predicted 1.98 to 2.46% risk of having QTc prolongation of >60 ms in all treatment settings. Although piperaquine administration resulted in QTc prolongation, no cardiovascular adverse events were found in these patients. Thus, the use of dihydroartemisinin-piperaquine should not be limited by this concern.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1128/AAC.01848-19