J. TarningE. A. AshleyN. LindegardhK. StepniewskaL. PhaiphunN. P J DayR. McGreadyM. AshtonF. NostenN. J. WhiteGoteborg University, Sahlgrenska AcademyShoklo Malaria Research UnitMahidol UniversityChurchill HospitalEpicentre2018-07-122018-07-122008-03-01Antimicrobial Agents and Chemotherapy. Vol.52, No.3 (2008), 1052-1061006648042-s2.0-40549113955https://repository.li.mahidol.ac.th/handle/123456789/19759The population pharmacokinetics of piperaquine in adults and children with uncomplicated Plasmodium falciparum malaria treated with two different dosage regimens of dihydroartemisinin-piperaquine were characterized. Piperaquine pharmacokinetics in 98 Burmese and Karen patients aged 3 to 55 years were described by a two-compartment disposition model with first-order absorption and interindividual random variability on all parameters and were similar with the three- and four-dose regimens. Children had a lower body weight-normalized oral clearance than adults, resulting in longer terminal elimination half-lives and higher total exposure to piperaquine (area under the concentration-time curve from 0 to 63 days [AUCday 0-63]). However, children had lower plasma concentrations in the therapeutically relevant posttreatment prophylactic period (AUCday 3-20) because of smaller body weight-normalized central volumes of distribution and shorter distribution half-lives. Our data lend further support to a simplified once-daily treatment regimen to improve treatment adherence and efficacy and indicate that weight-adjusted piperaquine doses in children may need to be higher than in adults. Copyright © 2008, American Society for Microbiology. All Rights Reserved.Mahidol UniversityMedicineArticleSCOPUS10.1128/AAC.00955-07