Walter Robert TaylorRichard M. HoglundPimnara PeerawaranunThuy Nhien NguyenTran Tinh HienArnaud TarantolaLorenz von SeidleinRupam TripuraThomas J. PetoArjen M. DondorpJordi LandierFrancois H.NostenFrank SmithuisKoukeo PhommasoneMayfong MayxaySoy Ty KheangChy SayKak NeerajLeang RitheaLek DysoleySim KhengSinoun MuthArantxa Roca-FeltrerMark DebackereRick M. FairhurstNgak SongPhilippe BuchyDidier MenardNicholas J. WhiteJoel TarningMavuto MukakaFaculty of Tropical Medicine, Mahidol UniversityUniversity Research Co., LLCAmsterdam Institute for Global Health and DevelopmentOxford University Clinical Research UnitFHI 360Sciences Economiques et Sociales de la Santé et Traitement de l'Information MédicaleMalaria ConsortiumInstitut Pasteur du CambodgeShoklo Malaria Research UnitNational Institute of Allergy and Infectious Diseases (NIAID)Mahosot Hospital, LaoNuffield Department of MedicineInstitut Pasteur, ParisAmsterdam UMC - University of AmsterdamAQUITY Global Inc.Myanmar Oxford Clinical Research UnitUniversity of Health SciencesMSF Belgium Cambodia Malaria ProgramGSK VaccinesNational Center for ParasitologyNational Institute of Public Health2022-08-042022-08-042021-12-01Malaria Journal. Vol.20, No.1 (2021)147528752-s2.0-85114678743https://repository.li.mahidol.ac.th/handle/123456789/77153Background: 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.Mahidol UniversityImmunology and MicrobiologyMedicineArticleSCOPUS10.1186/s12936-021-03886-w