Population Pharmacokinetics of Piperaquine in Young Ugandan Children Treated With Dihydroartemisinin-Piperaquine for Uncomplicated Malaria.
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.
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.|Department of Medicine, University of California San Francisco, San Francisco, California, USA.|Department of Clinical Pharmacy, University of California San Francisco, San Francisco, California, USA.
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Sambol
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.|Department of Medicine, University of California San Francisco, San Francisco, California, USA.
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Yan
Department of Clinical Pharmacy, University of California San Francisco, San Francisco, California, USA.|Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia.
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Creek
Department of Clinical Pharmacy, University of California San Francisco, San Francisco, California, USA.
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McCormack
Makerere University School of Medicine, Kampala, Uganda.
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Arinaitwe
Makerere University School of Medicine, Kampala, Uganda.
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Bigira
Makerere University School of Medicine, Kampala, Uganda.
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Wanzira
Makerere University School of Medicine, Kampala, Uganda.
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Kakuru
Centers for Global Health, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
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Tappero
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Lindegardh
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Tarning
Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.|Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
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Nosten
Department of Clinical Pharmacy, University of California San Francisco, San Francisco, California, USA.
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Aweeka
Yale School of Public Health and Medicine, New Haven, Connecticut, USA.
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Parikh
D000962:Antimalarials / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D037621:Artemisinins / Q000627:therapeutic use*; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D006801:Humans; D007223:Infant; D008288:Malaria / Q000188:drug therapy*; D011446:Prospective Studies; D011804:Quinolines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014454:Uganda; D010879:Piperazines
D000962:Antimalarials; D037621:Artemisinins; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines