Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria
Abstract Background In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal pati...
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| Format: | Article |
| Language: | English |
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BMC
2021-09-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-021-03886-w |
| _version_ | 1818736817327833088 |
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| author | Walter Robert Taylor Richard M. Hoglund Pimnara Peerawaranun Thuy Nhien Nguyen Tran Tinh Hien Arnaud Tarantola Lorenz von Seidlein Rupam Tripura Thomas J. Peto Arjen M. Dondorp Jordi Landier Francois H.Nosten Frank Smithuis Koukeo Phommasone Mayfong Mayxay Soy Ty Kheang Chy Say Kak Neeraj Leang Rithea Lek Dysoley Sim Kheng Sinoun Muth Arantxa Roca-Feltrer Mark Debackere Rick M. Fairhurst Ngak Song Philippe Buchy Didier Menard Nicholas J. White Joel Tarning Mavuto Mukaka |
| author_facet | Walter Robert Taylor Richard M. Hoglund Pimnara Peerawaranun Thuy Nhien Nguyen Tran Tinh Hien Arnaud Tarantola Lorenz von Seidlein Rupam Tripura Thomas J. Peto Arjen M. Dondorp Jordi Landier Francois H.Nosten Frank Smithuis Koukeo Phommasone Mayfong Mayxay Soy Ty Kheang Chy Say Kak Neeraj Leang Rithea Lek Dysoley Sim Kheng Sinoun Muth Arantxa Roca-Feltrer Mark Debackere Rick M. Fairhurst Ngak Song Philippe Buchy Didier Menard Nicholas J. White Joel Tarning Mavuto Mukaka |
| author_sort | Walter Robert Taylor |
| collection | DOAJ |
| description | Abstract Background In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax. Methods The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen. Results The proposed weight-based regimen has 5 dosing bands: (i) 5–7 kg, 5 mg, resulting in 0.71–1.0 mg/kg/day; (ii) 8–16 kg, 7.5 mg, 0.47–0.94 mg/kg/day; (iii) 17–40 kg, 15 mg, 0.38–0.88 mg/kg/day; (iv) 41–80 kg, 30 mg, 0.37–0.73 mg/kg/day; and (v) 81–100 kg, 45 mg, 0.45–0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6–11 months, 5 mg, 0.43–1.0 mg/kg/day; (ii) 1–5 years, 7.5 mg, 0.35–1.25 mg/kg/day; (iii) 6–14 years, 15 mg, 0.30–1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35–1.07 mg/kg/day. Conclusion The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens. |
| first_indexed | 2024-12-18T00:43:10Z |
| format | Article |
| id | doaj.art-99fc57599ac04492ad2d3235bd20aa6f |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-18T00:43:10Z |
| publishDate | 2021-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-99fc57599ac04492ad2d3235bd20aa6f2022-12-21T21:26:50ZengBMCMalaria Journal1475-28752021-09-0120111010.1186/s12936-021-03886-wDevelopment of weight and age-based dosing of daily primaquine for radical cure of vivax malariaWalter Robert Taylor0Richard M. Hoglund1Pimnara Peerawaranun2Thuy Nhien Nguyen3Tran Tinh Hien4Arnaud Tarantola5Lorenz von Seidlein6Rupam Tripura7Thomas J. Peto8Arjen M. Dondorp9Jordi Landier10Francois H.Nosten11Frank Smithuis12Koukeo Phommasone13Mayfong Mayxay14Soy Ty Kheang15Chy Say16Kak Neeraj17Leang Rithea18Lek Dysoley19Sim Kheng20Sinoun Muth21Arantxa Roca-Feltrer22Mark Debackere23Rick M. Fairhurst24Ngak Song25Philippe Buchy26Didier Menard27Nicholas J. White28Joel Tarning29Mavuto Mukaka30Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityOxford University Clinical Research Unit, Wellcome Trust Major Oversea ProgrammeCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of OxfordInstitut Pasteur du CambodgeMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityShoklo Malaria Research UnitCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of OxfordMyanmar Oxford Clinical Research UnitLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Mahosot HospitalLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Mahosot HospitalCenter for Health and Social Development (HSD), National Institute for Public Health (NIPH) and University Research Co., LLC (URC)Center for Health and Social Development (HSD), National Institute for Public Health (NIPH) and University Research Co., LLC (URC)University Research Co., LLC Washington DCNational Center for Parasitology, Entomology and Malaria ControlNational Center for Parasitology, Entomology and Malaria ControlNational Center for Parasitology, Entomology and Malaria ControlNational Center for Parasitology, Entomology and Malaria ControlMalaria ConsortiumMSF Belgium Cambodia Malaria ProgramLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthFHI 360 Cambodia Office, Keng Kang III Khan ChamkamonInstitut Pasteur du CambodgeInstitut Pasteur du CambodgeMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityAbstract Background In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax. Methods The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen. Results The proposed weight-based regimen has 5 dosing bands: (i) 5–7 kg, 5 mg, resulting in 0.71–1.0 mg/kg/day; (ii) 8–16 kg, 7.5 mg, 0.47–0.94 mg/kg/day; (iii) 17–40 kg, 15 mg, 0.38–0.88 mg/kg/day; (iv) 41–80 kg, 30 mg, 0.37–0.73 mg/kg/day; and (v) 81–100 kg, 45 mg, 0.45–0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6–11 months, 5 mg, 0.43–1.0 mg/kg/day; (ii) 1–5 years, 7.5 mg, 0.35–1.25 mg/kg/day; (iii) 6–14 years, 15 mg, 0.30–1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35–1.07 mg/kg/day. Conclusion The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.https://doi.org/10.1186/s12936-021-03886-wPrimaquineAllometric scalingAge-based dosingWeight-based dosingPlasmodium vivax |
| spellingShingle | Walter Robert Taylor Richard M. Hoglund Pimnara Peerawaranun Thuy Nhien Nguyen Tran Tinh Hien Arnaud Tarantola Lorenz von Seidlein Rupam Tripura Thomas J. Peto Arjen M. Dondorp Jordi Landier Francois H.Nosten Frank Smithuis Koukeo Phommasone Mayfong Mayxay Soy Ty Kheang Chy Say Kak Neeraj Leang Rithea Lek Dysoley Sim Kheng Sinoun Muth Arantxa Roca-Feltrer Mark Debackere Rick M. Fairhurst Ngak Song Philippe Buchy Didier Menard Nicholas J. White Joel Tarning Mavuto Mukaka Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria Malaria Journal Primaquine Allometric scaling Age-based dosing Weight-based dosing Plasmodium vivax |
| title | Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria |
| title_full | Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria |
| title_fullStr | Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria |
| title_full_unstemmed | Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria |
| title_short | Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria |
| title_sort | development of weight and age based dosing of daily primaquine for radical cure of vivax malaria |
| topic | Primaquine Allometric scaling Age-based dosing Weight-based dosing Plasmodium vivax |
| url | https://doi.org/10.1186/s12936-021-03886-w |
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