Publication: Population pharmacokinetics of piperaquine in Young Ugandan Children treated with dihydroartemisinin-piperaquine for uncomplicated malaria
Issued Date
2015-07-01
Resource Type
ISSN
15326535
00099236
00099236
DOI
Other identifier(s)
2-s2.0-84940554089
Rights
Mahidol University
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SCOPUS
Bibliographic Citation
Clinical Pharmacology and Therapeutics. Vol.98, No.1 (2015), 87-95
Suggested Citation
N. C. Sambol, L. Yan, D. J. Creek, S. A. McCormack, E. Arinaitwe, V. Bigira, H. Wanzira, A. Kakuru, J. W. Tappero, N. Lindegardh, J. Tarning, F. Nosten, F. T. Aweeka, S. Parikh Population pharmacokinetics of piperaquine in Young Ugandan Children treated with dihydroartemisinin-piperaquine for uncomplicated malaria. Clinical Pharmacology and Therapeutics. Vol.98, No.1 (2015), 87-95. doi:10.1002/cpt.104 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/36396
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Title
Population pharmacokinetics of piperaquine in Young Ugandan Children treated with dihydroartemisinin-piperaquine for uncomplicated malaria
Abstract
© 2015 American Society for Clinical Pharmacology and Therapeutics. This prospective trial investigated the population pharmacokinetics of piperaquine given with dihydroartemisinin to treat uncomplicated malaria in 107 Ugandan children 6 months to 2 years old, an age group previously unstudied. Current weight-based dosing does not adequately address physiological changes in early childhood. Patients were administered standard 3-day oral doses and provided 1,282 capillary plasma concentrations from 218 malaria episodes. Less than 30% of treatments achieved 57 ng/mL on day 7. A three-compartment model with first-order absorption described the data well. Age had a statistically significant effect (P < 0.005) on clearance/bioavailability in a model that accounts for allometric scaling. Simulations demonstrated that higher doses in all children, but especially in those with lower weight for age, are required for adequate piperaquine exposure, although safety and tolerance will need to be established. These findings support other evidence that both weight-and age-specific guidelines for piperaquine dosing in children are urgently needed.