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Characterization of an in vivo concentration-effect relationship for piperaquine in malaria chemoprevention
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2014 (English)In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 6, no 260, 260ra147- p.Article in journal (Refereed) Published
Abstract [en]

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 E-max relationship, 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.

Place, publisher, year, edition, pages
2014. Vol. 6, no 260, 260ra147- p.
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Pharmaceutical Sciences
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URN: urn:nbn:se:uu:diva-237913DOI: 10.1126/scitranslmed.3005311ISI: 000343920500004PubMedID: 25355697OAI: oai:DiVA.org:uu-237913DiVA: diva2:770687
Available from: 2014-12-11 Created: 2014-12-08 Last updated: 2017-12-05Bibliographically approved

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Bergstrand, MartinKarlsson, Mats O.

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