ABSTRACT
Tafenoquine (SB252263, previously known as WR 238605) is an investigational 8-aminoquinoline that is being co-developed as an antimalarial medication by Medicines for Malaria Venture and GlaxoSmithKline with the historical support of the US Army. Its structure is 2,6-dimethoxy-4-methyl-5-([3-trifluoromethyl]-phenoxy)-8-([4-amino-1-methylbutyl]amino) quinoline, as shown in Figure 181.1, with a formula of C24H28F3N3O3 · C4H6O4 and a molecular weight of 581.58 (succinate salt). It is better tolerated and can be given in higher dosages than its analog, primaquine. In clinical trials, tafenoquine has typically been formulated in tablet form containing 150, 200, or 400 mg of free base (188, 250, or 500 mg of succinate salt). Tafenoquine kills all stages of the malaria parasite and has demonstrated activity against Plasmodium falciparum and Plasmodium vivax in humans, as well as Plasmodium cynomolgi, Plasmodium berghei, and Plasmodium fragile in animals. Tafenoquine’s possible clinical indications could include the chemoprophylaxis of malaria, treatment of relapsing malaria, and blocking of malaria transmission. Its most common adverse events are gastrointestinal intolerance and transient elevation of liver enzymes, especially at the highest tolerated doses. Like primaquine, tafenoquine can cause severe hemolysis in persons deficient in glucose-6-phosphate dehydrogenase (G6PD) and causes a reversible elevation of methemoglobinemia. Its mechanism of action is unknown. Chemical structure of tafenoquine succinate. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781315152110/08d8042d-9481-4a8d-8c27-9bd589f6de6b/content/fig181_1.tif" xmlns:xlink="https://www.w3.org/1999/xlink"/>
