Within-host modeling of primaquine-induced hemolysis in hemizygote glucose-6-phosphate dehydrogenase deficient healthy volunteers
3
Issued Date
2025-04-01
Resource Type
ISSN
00664804
eISSN
10986596
Scopus ID
2-s2.0-105001937461
Pubmed ID
39992119
Journal Title
Antimicrobial Agents and Chemotherapy
Volume
69
Issue
4
Rights Holder(s)
SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy Vol.69 No.4 (2025)
Suggested Citation
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. Within-host modeling of primaquine-induced hemolysis in hemizygote glucose-6-phosphate dehydrogenase deficient healthy volunteers. Antimicrobial Agents and Chemotherapy Vol.69 No.4 (2025). doi:10.1128/aac.01549-24 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/109513
Title
Within-host modeling of primaquine-induced hemolysis in hemizygote glucose-6-phosphate dehydrogenase deficient healthy volunteers
Author's Affiliation
Infectious Diseases Data Observatory
Faculty of Tropical Medicine, Mahidol University
Mahidol Oxford Tropical Medicine Research Unit
Melbourne School of Population and Global Health
The Peter Doherty Institute for Infection and Immunity
Menzies School of Health Research
Nuffield Department of Medicine
Grampians Health
Faculty of Tropical Medicine, Mahidol University
Mahidol Oxford Tropical Medicine Research Unit
Melbourne School of Population and Global Health
The Peter Doherty Institute for Infection and Immunity
Menzies School of Health Research
Nuffield Department of Medicine
Grampians Health
Corresponding Author(s)
Other Contributor(s)
Abstract
Primaquine 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).