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The clinical pharmacology of tafenoquine in the radical cure of Plasmodium vivax malaria: An individual patient data meta-analysis

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dc.contributor.author Watson, James A.
dc.contributor.author Commons, Robert J.
dc.contributor.author Tarning, Joel
dc.contributor.author Simpson, Julie A.
dc.contributor.author Llanos Cuentas, Elmer Alejandro
dc.contributor.author Lacerda, Marcus V. G.
dc.contributor.author Green, Justin A.
dc.contributor.author Koh, Gavin C. K. W.
dc.contributor.author Chu, Cindy S.
dc.contributor.author Nosten, Francois H.
dc.contributor.author Price, Richard N.
dc.contributor.author Day, Nicholas P. J.
dc.contributor.author White, Nicholas J.
dc.date.accessioned 2023-01-06T13:40:12Z
dc.date.available 2023-01-06T13:40:12Z
dc.date.issued 2022
dc.identifier.uri https://hdl.handle.net/20.500.12866/13004
dc.description.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. en_US
dc.language.iso eng
dc.publisher eLife Sciences Publications
dc.relation.ispartofseries eLife
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Clinical pharmacology en_US
dc.subject Tafenoquine en_US
dc.subject Plasmodium vivax en_US
dc.subject Malaria en_US
dc.subject Meta-analysis en_US
dc.title The clinical pharmacology of tafenoquine in the radical cure of Plasmodium vivax malaria: An individual patient data meta-analysis en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.7554/eLife.83433
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.03
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.03
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.04
dc.relation.issn 2050-084X


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