Characterization of an in vivo concentration-effect relationship for piperaquine in malaria chemoprevention
2014 (English)In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 6, no 260, 260ra147- p.Article in journal (Refereed) Published
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.
IdentifiersURN: urn:nbn:se:uu:diva-237913DOI: 10.1126/scitranslmed.3005311ISI: 000343920500004PubMedID: 25355697OAI: oai:DiVA.org:uu-237913DiVA: diva2:770687