Pharmacokinetic properties of single-dose primaquine in Papua New Guinean children: Feasibility of abbreviated high-dose regimens for radical cure of vivax malaria
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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Journal Article |
| Published: |
American Society for Microbiology
2014
|
| Online Access: | http://hdl.handle.net/20.500.11937/9960 |
| _version_ | 1848746100081557504 |
|---|---|
| author | Moore, Brioni Salman, S. Benjamin, J. Page-Sharp, Madhu Robinson, L. Waita, E. Batty, Kevin Siba, P. Mueller, I. Davis, T. Betuela, I. |
| author_facet | Moore, Brioni Salman, S. Benjamin, J. Page-Sharp, Madhu Robinson, L. Waita, E. Batty, Kevin Siba, P. Mueller, I. Davis, T. Betuela, I. |
| author_sort | Moore, Brioni |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T06:27:53Z |
| format | Journal Article |
| id | curtin-20.500.11937-9960 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:27:53Z |
| publishDate | 2014 |
| publisher | American Society for Microbiology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-99602023-02-22T06:24:15Z Pharmacokinetic properties of single-dose primaquine in Papua New Guinean children: Feasibility of abbreviated high-dose regimens for radical cure of vivax malaria Moore, Brioni Salman, S. Benjamin, J. Page-Sharp, Madhu Robinson, L. Waita, E. Batty, Kevin Siba, P. Mueller, I. Davis, T. Betuela, I. 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. 2014 Journal Article http://hdl.handle.net/20.500.11937/9960 10.1128/AAC.01437-13 American Society for Microbiology unknown |
| spellingShingle | Moore, Brioni Salman, S. Benjamin, J. Page-Sharp, Madhu Robinson, L. Waita, E. Batty, Kevin Siba, P. Mueller, I. Davis, T. Betuela, I. Pharmacokinetic properties of single-dose primaquine in Papua New Guinean children: Feasibility of abbreviated high-dose regimens for radical cure of vivax malaria |
| title | Pharmacokinetic properties of single-dose primaquine in Papua New Guinean children: Feasibility of abbreviated high-dose regimens for radical cure of vivax malaria |
| title_full | Pharmacokinetic properties of single-dose primaquine in Papua New Guinean children: Feasibility of abbreviated high-dose regimens for radical cure of vivax malaria |
| title_fullStr | Pharmacokinetic properties of single-dose primaquine in Papua New Guinean children: Feasibility of abbreviated high-dose regimens for radical cure of vivax malaria |
| title_full_unstemmed | Pharmacokinetic properties of single-dose primaquine in Papua New Guinean children: Feasibility of abbreviated high-dose regimens for radical cure of vivax malaria |
| title_short | Pharmacokinetic properties of single-dose primaquine in Papua New Guinean children: Feasibility of abbreviated high-dose regimens for radical cure of vivax malaria |
| title_sort | pharmacokinetic properties of single-dose primaquine in papua new guinean children: feasibility of abbreviated high-dose regimens for radical cure of vivax malaria |
| url | http://hdl.handle.net/20.500.11937/9960 |