Reduced Exposure to Piperaquine, Compared to Adults, in Young Children Receiving Dihydroartemisinin-Piperaquine as Malaria Chemoprevention

Meghan E Whalen, Richard Kajubi, Nona Chamankhah, Liusheng Huang, Francis Orukan, Erika Wallender, Moses R Kamya, Grant Dorsey, Prasanna Jagannathan, Philip J Rosenthal, Norah Mwebaza, Francesca T Aweeka, Meghan E Whalen, Richard Kajubi, Nona Chamankhah, Liusheng Huang, Francis Orukan, Erika Wallender, Moses R Kamya, Grant Dorsey, Prasanna Jagannathan, Philip J Rosenthal, Norah Mwebaza, Francesca T Aweeka

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 with adults, DHA area under the concentration-time curve (AUC0-8 hr ) was 52% higher at 32 weeks and comparable at 104 weeks. Compared with adults, piperaquine AUC0-21 d 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 with adults and lower at 104 compared with 32 weeks. Piperaquine exposure was lower in young children compared with adults, and lower at 104 compared with 32 weeks of age, suggesting a need for age-based DHA-piperaquine dose optimization for chemoprevention.

Trial registration: ClinicalTrials.gov NCT02163447.

Conflict of interest statement

CONFLICT OF INTEREST: The authors declared no competing interests for this work.

© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.

Figures

Figure 1.
Figure 1.
Enrollment and completion of intensive PK studies from trials evaluating DHA- piperaquine as IPTi for malaria; DP denotes DHA-piperaquine; SP, sulfadoxine-pyrimethamine; PK, pharmacokinetics; DHA, dihydroartemisinin; PQ, piperaquine. *Adult data previously reported (14).
Figure 2.
Figure 2.
Plasma concentration-time profile of DHA (A) and piperaquine (B) in children aged 104 weeks (black line) and 32 weeks (red line) and postpartum women (green line). Data is reported as median (IQR).
Figure 3.
Figure 3.
Correlation of changes in the QTcB interval and pharmacokinetic exposure of piperaquine. AUC denotes area under the concentration vs. time curve to 21 days.

Source: PubMed

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