Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic Study
dc.contributor.author | Batty, Kevin | |
dc.contributor.author | Salman, Sam | |
dc.contributor.author | Moore, Brioni | |
dc.contributor.author | Benjamin, John | |
dc.contributor.author | Lee, Sook Ting | |
dc.contributor.author | Page-Sharp, Madhu | |
dc.contributor.author | Pitus, Nolene | |
dc.contributor.author | Ilett, Kenneth | |
dc.contributor.author | Mueller, Ivo | |
dc.contributor.author | Hombhanje, Francis | |
dc.contributor.author | Siba, Peter | |
dc.contributor.author | Davis, Timothy | |
dc.date.accessioned | 2017-01-30T13:54:12Z | |
dc.date.available | 2017-01-30T13:54:12Z | |
dc.date.created | 2013-03-04T20:00:46Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | Batty, 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. | |
dc.identifier.uri | http://hdl.handle.net/20.500.11937/36181 | |
dc.identifier.doi | 10.1128/AAC.06250-11 | |
dc.description.abstract |
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.publisher | American Society for Microbiology | |
dc.title | Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic Study | |
dc.type | Journal Article | |
dcterms.source.volume | 56 | |
dcterms.source.number | 5 | |
dcterms.source.startPage | 2472 | |
dcterms.source.endPage | 2484 | |
dcterms.source.issn | 0066-4804 | |
dcterms.source.title | Antimicrobial Agents and Chemotherapy | |
curtin.department | ||
curtin.accessStatus | Open access via publisher |