The clinical pharmacology of tafenoquine in the radical cure of Plasmodium vivax malaria: An individual patient data meta-analysis
Issued Date
2022-12-01
Resource Type
eISSN
2050084X
Scopus ID
2-s2.0-85143644288
Pubmed ID
36472067
Journal Title
eLife
Volume
11
Rights Holder(s)
SCOPUS
Bibliographic Citation
eLife Vol.11 (2022)
Suggested Citation
Watson J.A. The clinical pharmacology of tafenoquine in the radical cure of Plasmodium vivax malaria: An individual patient data meta-analysis. eLife Vol.11 (2022). doi:10.7554/ELIFE.83433 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83510
Title
The clinical pharmacology of tafenoquine in the radical cure of Plasmodium vivax malaria: An individual patient data meta-analysis
Author(s)
Author's Affiliation
WorldWide Antimalarial Resistance Network
Faculty of Tropical Medicine, Mahidol University
Oxford University Clinical Research Unit
Melbourne School of Population and Global Health
Universidad Peruana Cayetano Heredia, Instituto de Medicina Tropical Alexander von Humboldt
Northwick Park Hospital
Menzies School of Health Research
GlaxoSmithKline plc.
Mahidol University
Nuffield Department of Medicine
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Faculty of Tropical Medicine, Mahidol University
Oxford University Clinical Research Unit
Melbourne School of Population and Global Health
Universidad Peruana Cayetano Heredia, Instituto de Medicina Tropical Alexander von Humboldt
Northwick Park Hospital
Menzies School of Health Research
GlaxoSmithKline plc.
Mahidol University
Nuffield Department of Medicine
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Other Contributor(s)
Abstract
Tafenoquine is a newly licensed antimalarial drug for the radical cure of Plasmodium vivax malaria. The mechanism of action and optimal dosing are uncertain. We pooled individual data from 1102 patients and 72 healthy volunteers studied in the pre-registration trials. We show that tafenoquine dose is the primary determinant of efficacy. Under an Emax model, we estimate the currently recommended 300 mg dose in a 60 kg adult (5 mg/kg) results in 70% of the maximal obtainable hypnozoiticidal effect. Increasing the dose to 7.5 mg/kg (i.e. 450 mg) would result in 90% reduction in the risk of P. vivax recurrence. After adjustment for dose, the tafenoquine terminal elimination half-life, and day 7 methaemoglobin concentration, but not the parent compound exposure, were also associated with recurrence. These results suggest that the production of oxidative metabolites is central to tafenoquine’s hypnozoiticidal efficacy. Clinical trials of higher tafenoquine doses are needed to characterise their efficacy, safety and tolerability.