Publication: Characterization of an in vivo concentration-effect relationship for piperaquine in malaria chemoprevention
Issued Date
2014-01-01
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ISSN
19466242
19466234
19466234
Other identifier(s)
2-s2.0-84908565358
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Mahidol University
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SCOPUS
Bibliographic Citation
Science Translational Medicine. Vol.6, No.260 (2014)
Suggested Citation
Martin Bergstrand, François Nosten, Khin Maung Lwin, Mats O. Karlsson, Nicholas J. White, Joel Tarning Characterization of an in vivo concentration-effect relationship for piperaquine in malaria chemoprevention. Science Translational Medicine. Vol.6, No.260 (2014). doi:10.1126/scitranslmed.3005311 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/34755
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Title
Characterization of an in vivo concentration-effect relationship for piperaquine in malaria chemoprevention
Abstract
A randomized, placebo-controlled trial conducted on the northwest border of Thailand compared malaria chemoprevention with monthly or bimonthly standard 3-day treatment regimens of dihydroartemisinin-piperaquine. Healthy adult male subjects (N = 1000) were followed weekly during 9 months of treatment. Using nonlinear mixed-effects modeling, the concentration-effect relationship for the malaria-preventive effect of piperaquine was best characterized with a sigmoidal Emaxrelationship, where plasma concentrations of 6.7 ng/ml [relative standard error (RSE), 23%] and 20 ng/ml were found to reduce the hazard of acquiring a malaria infection by 50% [that is, median inhibitory concentration (IC50)] and 95% (IC95), respectively. Simulations of monthly dosing, based on the final model and published pharmacokinetic data, suggested that the incidence of malaria infections over 1 year could be reduced by 70% with a recently suggested dosing regimen compared to the current manufacturer's recommendations for small children (8 to 12 kg). This model provides a rational framework for piperaquine dose optimization in different patient groups.