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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/58113
Title: Pooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in african patients with uncomplicated falciparum malaria
Authors: 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
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
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jul-2020
Citation: Antimicrobial Agents and Chemotherapy. Vol.64, No.7 (2020)
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.
URI: http://repository.li.mahidol.ac.th/dspace/handle/123456789/58113
metadata.dc.identifier.url: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85087095233&origin=inward
ISSN: 10986596
00664804
Appears in Collections:Scopus 2020

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