Watson J.A.Mehdipour P.Moss R.Jittamala P.Zaloumis S.Price D.J.Dini S.Hanboonkunupakarn B.Leungsinsiri P.Poovorawan K.Chotivanich K.Bancone G.Commons R.J.Day N.P.J.Pukrittayakamee S.Taylor W.R.J.White N.J.Simpson J.A.Mahidol University2025-04-142025-04-142025-04-01Antimicrobial Agents and Chemotherapy Vol.69 No.4 (2025)00664804https://repository.li.mahidol.ac.th/handle/123456789/109513Primaquine is the only widely available drug to prevent relapses of Plasmodium vivax malaria. Primaquine is underused because of concerns over oxidant hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficiency. A pharmacometric trial showed that ascending-dose radical cure primaquine regimens causing ‘slow burn’ hemolysis were safe in G6PD-deficient Thai and Burmese male volunteers. We developed and calibrated a within-host model of primaquine hemolysis in G6PD deficiency, using detailed serial hemoglobin and reticulocyte count data from 23 hemizygote deficient volunteers given ascending-dose primaquine (1,523 individual measurements over 656 unique time points). We estimate that primaquine doses of ~0.75 mg base/kg reduce the circulating lifespan of deficient erythrocytes by ~30 days in individuals with common Southeast Asian G6PD variants. We predict that 5 mg/kg primaquine total dose can be administered safely to G6PD-deficient individuals over 14 days with expected hemoglobin drops of 18 to 43% (2.7 to 6.5 g/dL drop from a baseline of 15 g/dL).Pharmacology, Toxicology and PharmaceuticsMedicineArticleSCOPUS10.1128/aac.01549-242-s2.0-1050019374611098659639992119