Martin BergstrandFrançois NostenKhin Maung LwinMats O. KarlssonNicholas J. WhiteJoel TarningUppsala UniversitetMahidol UniversityNuffield Department of Clinical MedicineShoklo Malaria Research Unit2018-11-092018-11-092014-01-01Science Translational Medicine. Vol.6, No.260 (2014)19466242194662342-s2.0-84908565358https://repository.li.mahidol.ac.th/handle/20.500.14594/34755A 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.Mahidol UniversityMedicineArticleSCOPUS10.1126/scitranslmed.3005311