Publication: Pooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in african patients with uncomplicated falciparum malaria
Issued Date
2020-07-01
Resource Type
ISSN
10986596
00664804
00664804
Other identifier(s)
2-s2.0-85087095233
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.64, No.7 (2020)
Suggested Citation
Thanaporn Wattanakul, Bernhards Ogutu, Abdunoor M. Kabanywanyi, Kwaku Poku Asante, Abraham Oduro, Alex Adjei, Ali Sie, Esperanca Sevene, Eusebio MacEte, Guillaume Compaore, Innocent Valea, Isaac Osei, Markus Winterberg, Margaret Gyapong, Martin Adjuik, Salim Abdulla, Seth Owusu-Agyei, Nicholas J. White, Nicholas P.J. Day, Halidou Tinto, Rita Baiden, Fred Binka, Joel Tarning Pooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in african patients with uncomplicated falciparum malaria. Antimicrobial Agents and Chemotherapy. Vol.64, No.7 (2020). doi:10.1128/AAC.01848-19 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/58113
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Title
Pooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in african patients with uncomplicated falciparum malaria
Author(s)
Thanaporn Wattanakul
Bernhards Ogutu
Abdunoor M. Kabanywanyi
Kwaku Poku Asante
Abraham Oduro
Alex Adjei
Ali Sie
Esperanca Sevene
Eusebio MacEte
Guillaume Compaore
Innocent Valea
Isaac Osei
Markus Winterberg
Margaret Gyapong
Martin Adjuik
Salim Abdulla
Seth Owusu-Agyei
Nicholas J. White
Nicholas P.J. Day
Halidou Tinto
Rita Baiden
Fred Binka
Joel Tarning
Bernhards Ogutu
Abdunoor M. Kabanywanyi
Kwaku Poku Asante
Abraham Oduro
Alex Adjei
Ali Sie
Esperanca Sevene
Eusebio MacEte
Guillaume Compaore
Innocent Valea
Isaac Osei
Markus Winterberg
Margaret Gyapong
Martin Adjuik
Salim Abdulla
Seth Owusu-Agyei
Nicholas J. White
Nicholas P.J. Day
Halidou Tinto
Rita Baiden
Fred Binka
Joel Tarning
Other Contributor(s)
University of Health and Allied Sciences, Ghana
Centre de Recherche en Sante de Nouna
Navrongo Health Research Center
Kintampo Health Research Centre
Ifakara Health Institute
Kenya Medical Research Institute
Mahidol University
Nuffield Department of Medicine
Clinical Research Unit of Nanoro (IRSS-URCN)
Dodowa Health Research Centre
WorldWide Antimalarial Resistance Network
Centro de Investigação em Saúde de Manhiça
INDEPTH Network
Centre de Recherche en Sante de Nouna
Navrongo Health Research Center
Kintampo Health Research Centre
Ifakara Health Institute
Kenya Medical Research Institute
Mahidol University
Nuffield Department of Medicine
Clinical Research Unit of Nanoro (IRSS-URCN)
Dodowa Health Research Centre
WorldWide Antimalarial Resistance Network
Centro de Investigação em Saúde de Manhiça
INDEPTH Network
Abstract
Copyright © 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.