Pharmacokinetic properties of single-dose primaquine in Papua New Guinean children: Feasibility of abbreviated high-dose regimens for radical cure of vivax malaria
|dc.identifier.citation||Moore, Brioni R. and Salman, Sam and Benjamin, John and Page-Sharp, Madhu and Robinson, Leanne J. and Waita, Elizabeth and Batty, Kevin T. and Siba, Peter and Mueller, Ivo and Davis, Timothy M. E. and Betuela, Inoni. 2014. Pharmacokinetic properties of single-dose primaquine in Papua New Guinean children: Feasibility of abbreviated high-dose regimens for radical cure of vivax malaria. Antimicrobial Agents and Chemotherapy. 58 (1): pp. 432-439.|
Since conventional 14-day primaquine (PMQ) radical cure of vivax malaria is associated with poor compliance and as total dose, not therapy duration, determines efficacy, a preliminary pharmacokinetic study of two doses (0.5 and 1.0 mg/kg) was conducted in 28 healthy glucose-6-phosphate dehydrogenase-normal Papua New Guinean children aged 5-12 years to facilitate development of abbreviated high-dose regimens. Dosing was with food and directly observed, and venous blood samples were drawn over 168 h post-dose. Detailed safety monitoring was performed including hepatorenal function, and hemoglobin and methemaglobin concentrations. Plasma concentrations of PMQ and its metabolite carboxyprimaquine (CPMQ) were determined by liquid-chromatography/mass spectrometry and analyzed using population pharmacokinetic methods. The derived models were used in simulations. Both single-dose regimens were well tolerated with no changes in safety parameters. The mean PMQ central volume of distribution and clearance relative to bioavailability (200 liters/70 kg and 24.6 liters/h/70 kg) were within published ranges for adults. The median predicted maximal concentration (Cmax) for both PMQ and CPMQ after last dose of a 1.0 mg/kg 7-day PMQ regimen were approximately double those at the end of 14 days of 0.5 mg/kg daily, while a 1.0 mg/kg twice daily regimen resulted in a 2.38 and 3.33 times higher Cmax for PMQ and CPMQ, respectively. All predicted median Cmax concentrations were within ranges in adult high-dose studies that also showed acceptable safety and tolerability. The present pharmacokinetic data, the first for PMQ in children, show that further studies of abbreviated high-dose regimens are feasible in this age-group.
|dc.publisher||American Society for Microbiology|
|dc.title||Pharmacokinetic properties of single-dose primaquine in Papua New Guinean children: Feasibility of abbreviated high-dose regimens for radical cure of vivax malaria|
|dcterms.source.title||Antimicrobial Agents and Chemotherapy|
|curtin.accessStatus||Open access via publisher|