Piperaquine antimalarial

Oil-soluble artemether and water-soluble sodium artesunate were developed and approved as new antimalarial drugs by the Chinese authorities in 1987. After 1992, dihydroartemisinin, Coartem (a combination of artemether and benflumetol), and Artekin (a combination of dihydroartemisinin and piperaquine) were also marketed as new antimalarial dmgs. Since then, over 10 million malaria patients on a global scale have been cured after administration of these drugs. As a result, artemether, artesunate, and Coartem were added by the World Health Organization to the ninth, eleventh, and twelfth Essential Medicine List respectively. 

In the last few years, variations on the basic stracmre have been launched in combination with other antimalarials (usually variations on the chloroquine structure) such as dihydroartemismin and piperaquine phosphate (Artekin), artemether and lumefantrine (Coartem), artesunate/mefloquine (Artequin) and artesunate, sulfamethoxypyrazine, and pyrimethamine (Co-Arinate). Currently, there is another fixed dose combination with an artemisinin derivative in clinical trials, pyronaridine/artesunate (Pyramax in Phase III). However, the tri-oxo scaffold system in artemisinins has led to the synthesis of not only artemisinin variations but to totally synthetic molecules with the trioxane moiety included, such as arterolane tosylate (81). This compound is in Phase II trials as a single agent under Ranbaxy and is in Phase I trials in combination with piperaquine phosphate, also under Ranbaxy. 

Taming J, Bergqvist Y, Day NP, Bergquist J, Arvidsson B, White NJ, Ashton M, Lindegardh N. Characterization of human urinary metabolites of the antimalarial piperaquine. Drug Metab Dispos 2006 34 2011-2019. 

Davis, T. M. E. Hamzah, J. Ilett, K. R Karunajeewa, H. A. Reeder, J. C. Batty, K. T. Hackett, S. Barrett, P. In vitro interactions between piperaquine, dihydroartemisinin, and other conventional and novel antimalarial drugs. Antimicrob. Agents Chemother. 2006, 50, 2883-2885. 

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