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Reduced exposure to piperaquine in young children, compared to adults, in children receiving dihydroartemisinin-piperaquine as malaria chemoprevention. Clinical pharmacology and therapeutics Whalen, M. E., Kajubi, R. n., Chamankhah, N. n., Huang, L. n., Orukan, F. n., Wallender, E. n., Kamya, M. R., Dorsey, G. n., Jagannathan, P. n., Rosenthal, P. J., Mwebaza, N. n., Aweeka, F. T. 2019

Abstract

Dihydroartemisinin (DHA)-piperaquine is being evaluated as intermittent preventive therapy for malaria, but dosing has not been optimized for children. We assessed exposure to DHA and piperaquine in Ugandan children at two ages during infancy. Intensive sampling was performed in 32 children at 32 weeks of age, 31 children at 104 weeks, and 30 female adult controls. Compared to adults, DHA area under the concentration time curve (AUC0-8hr ) was 52% higher at 32 weeks and comparable at 104 weeks. Compared to adults, piperaquine AUC0-21d was 35% lower at 32 weeks and 53% lower at 104 weeks. Terminal piperaquine concentrations on Days 7, 14, and 21 were lower in children compared to adults and lower at 104 compared to 32 weeks. Piperaquine exposure was lower in young children compared to adults, and lower at 104 compared to 32 weeks of age, suggesting a need for age-based DHA-piperaquine dose optimization for chemoprevention. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/cpt.1534

View details for PubMedID 31173649