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dc.contributor.authorBatty, Kevin
dc.contributor.authorSalman, Sam
dc.contributor.authorMoore, Brioni
dc.contributor.authorBenjamin, John
dc.contributor.authorLee, Sook Ting
dc.contributor.authorPage-Sharp, Madhu
dc.contributor.authorPitus, Nolene
dc.contributor.authorIlett, Kenneth
dc.contributor.authorMueller, Ivo
dc.contributor.authorHombhanje, Francis
dc.contributor.authorSiba, Peter
dc.contributor.authorDavis, Timothy
dc.identifier.citationBatty, Kevin and Salman, Sam and Moore, Brioni and Benjamin, John and Lee, Sook Ting and Page-Sharp, Madhu and Pitus, Nolene and Ilett, Kenneth and Mueller, Ivo and Hombhanje, Francis and Siba, Peter and Davis, Timothy. 2012. Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic Study. Antimicrobial Agents and Chemotherapy 56 (5): pp. 2472-2484.

Artemisinin-naphthoquine (ART-NQ) is a coformulated antimalarial therapy marketed as a single-dose treatment in Papua New Guinea and other tropical countries. To build on limited knowledge of the pharmacokinetic properties of the components, especially the tetra-aminoquinoline NQ, we studied ART-NQ disposition in Papua New Guinea children aged 5 to 12 years with uncomplicated malaria, comparing a single dose (15 and 6 mg/kg of body weight) administered with water (group 1; n = 13), a single dose (22 and 9 mg/kg) with milk (group 2) (n = 17), and two daily doses of 22 and 9 mg/kg with water (group 3; n = 16). The plasma NQ concentration was assayed by high-performance liquid chromatography, and the plasma ART concentration was assayed using liquid chromatography-mass spectrometry. Population-based multicompartment pharmacokinetic models for NQ and ART were developed. NQ disposition was best characterized by a three-compartment model with a mean absorption half-life (t1/2) of 1.0 h and predicted median maximum plasma concentrations that ranged as high as 57 μg/liter after the second dose in group 3. The mean NQ elimination t1/2 was 22.8 days; clearance relative to bioavailability (CL/F) was 1.1 liters/h/kg; and volume at steady state relative to bioavailability (Vss/F) was 710 liters/kg. Administration of NQ with fat (8.5 g; 615 kJ) versus water was associated with 25% increased bioavailability. ART disposition was best characterized by a two-compartment model with a mean CL/F (4.1 liters/h/kg) and V/F (21 liters/kg) similar to those of previous studies. There was a 77% reduction in the bioavailability of the second ART dose (group 3). NQ has pharmacokinetic properties that confirm its potential as an artemisinin partner drug for treatment of uncomplicated pediatric malaria.

dc.publisherAmerican Society for Microbiology
dc.titleArtemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic Study
dc.typeJournal Article
dcterms.source.titleAntimicrobial Agents and Chemotherapy
curtin.accessStatusOpen access via publisher

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