Within-host modeling of primaquine-induced hemolysis in hemizygote glucose-6-phosphate dehydrogenase deficient healthy volunteers
Year: 2025
Type: article
Abstract: 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). CLINICAL TRIALS This study is registered with the Thai Clinical Trials Registry (TCTR) as TCTR20170830002 a nd TCTR20220317004 .
DOI: 10.1128/aac.01549-24
Authors: James A. Watson, Parinaz Mehdipour, Robert Moss, Podjanee Jittamala, Sophie Zaloumis, David J. Price, Saber Dini, Borimas Hanboonkunupakarn, Pawanrat Leungsinsiri, Kittiyod Poovorawan, Kesinee Chotivanich, Germana Bancone, Robert J. Commons, Nicholas P. J. Day, Sasithon Pukrittayakamee, Walter R. J. Taylor, Nicholas J. White, Julie A. Simpson
Institutions: University of Oxford, Infectious Diseases Data Observatory, The University of Melbourne, Mahidol University, Mahidol Oxford Tropical Medicine Research Unit, Peter Doherty Institute, Shoklo Malaria Research Unit, Charles Darwin University, Menzies School of Health Research, Grampians Health
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Awards: MASTER-MAP: Modern Acceleration STrategies for ERadication of Malaria in the Asia-Pacific, G2347075150, Accelerating to zero: targeting roadblocks to achieve malaria elimination, Improving the evaluation of severe malaria, Optimising treatment and prevention strategies to accelerate malaria elimination, Assessing the tolerability of a potentially safer radical curative regimen of primaquine in healthy volunteers with glucose 6 phosphate dehydrogenase, Advancing the radical cure of Plasmodium vivax malaria through optimal antimalarial regimens, Improving the treatment of malaria., Improving the evaluation of severe malaria, G9000302673
OpenAlex ID: W4407874553