1. Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria
- Author
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Jordi Landier, Thomas J. Peto, Frank Smithuis, Mavuto Mukaka, Mark Debackere, Walter R. J. Taylor, Lorenz von Seidlein, Arnaud Tarantola, Tran Tinh Hien, Arjen M. Dondorp, Rupam Tripura, Arantxa Roca-Feltrer, Koukeo Phommasone, Pimnara Peerawaranun, Sim Kheng, François Nosten, Nicholas J. White, Philippe Buchy, Joel Tarning, Sinoun Muth, Lek Dysoley, Soy Ty Kheang, Thuy Nguyen, Didier Menard, Ngak Song, Chy Say, Leang Rithea, Mayfong Mayxay, Kak Neeraj, Rick M. Fairhurst, Richard M. Hoglund, Intensive Care Medicine, Graduate School, Radiology and Nuclear Medicine, Mahidol University [Bangkok], University of Oxford, Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), VU University Medical Center [Amsterdam], Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Myanmar Oxford Clinical Research Unit [Yangon, Myanmar], Mahosot Hospital [Vientiane, Laos], Amsterdam Institute for Global Health & Development [Amsterdam, The Netherlands], University of Health Sciences [Vientiane, Laos] (UHS), National Institute of Public Health [Phnom Penh, Cambodge], AQUITY Global Inc [Potomac, MD, USA], University Research Co. [Washington, MD, USA] (URC), National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Malaria Consortium [London, UK] (MCL), MSF Belgium Cambodia Malaria Program [Phnom Penh, Cambodia], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Keng Kang III Khan Chamkamon [Phnom Penh, Cambodia], GSK Vaccines [Singapore, Singapore], Génétique du paludisme et résistance - Malaria Genetics and Resistance, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), This work was partly supported by a Wellcome Innovator award (WT-iTP-2018/001), but the Wellcome Trust was not involved in any aspect of this study., Malbec, Odile, University of Oxford [Oxford], Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,Primaquine ,[SDV]Life Sciences [q-bio] ,RC955-962 ,Plasmodium vivax ,Infectious and parasitic diseases ,RC109-216 ,0302 clinical medicine ,Arctic medicine. Tropical medicine ,030212 general & internal medicine ,Allometric scaling ,Child ,Aged, 80 and over ,biology ,Dosing regimen ,Age Factors ,Middle Aged ,3. Good health ,[SDV] Life Sciences [q-bio] ,Infectious Diseases ,Child, Preschool ,Female ,medicine.drug ,Adult ,Adolescent ,030231 tropical medicine ,Drug Administration Schedule ,03 medical and health sciences ,Antimalarials ,Young Adult ,Animal science ,Pharmacokinetics ,Age-based dosing ,medicine ,Malaria, Vivax ,Humans ,Dosing ,Aged ,business.industry ,Research ,Weight-based dosing ,Body Weight ,Infant ,biology.organism_classification ,Target dose ,Regimen ,Vivax malaria ,Parasitology ,business - 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.
- Published
- 2021