Dihydroartemisinin-piperaquine

Three currently-used artemisinin based combination therapies (ACT) artesunate-mefloquine, artemether-lumefantrine and dihydroartemisinin-piperaquine, have been proven highly simple, safe and effective in the treatment of multidrug resistant P. falciparum malaria. 

Dihydroartemisinin-piperaquine has been proved highly effective and well tolerated in South-East Asia. It is a four dose regimen 4 tablets on the 1st day and 2 tablets on the 2nd and 3rd day or 3 tablets per day for 3 days. 

Denis MB, Davis TM, Hewitt S, Incardona S, Nimol K, Fandeur T, Poravuth Y, Lim C, Socheat D. Efficacy and safety of dihydroartemisinin-piperaquine (Artekin) in Cambodian children and adults with uncomplicated falciparum malaria. Clin Infect Dis 2002 35(12) 1469-76. 

A prospective open-label, randomised trial comparing 14days of primaquine (0.25 mg base/kg) with either artensunate-amodiaquine or dihydroartemisinin-piperaquine (DHP) for the treatment of uncomplicated monoinfection with Plasmodium vivax malaria was performed Patients were randomised and given treatments without testing for G6PD status. Of the 331 patients, intravascular haemolysis occurred in 5 patients, of which 3 were males hemizygous for the G6PD-Mahidol mutation. Minor side effects were more frequent with artensunate-amodiaquine. 

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. 

The novel combination (Artekin ) of dihydroartemisinin and piperaquine has been assessed in 106 patients (76 children and 30 adults) with uncomplicated Plasmodium falciparum malaria in Cambodia (19). The respective doses of dihydroartemisinin and piperaquine, which were given at 0,8, 24, and 32 hours, were 9.1 mg/kg and 74 mg/kg in children and 6.6 and 53 mg/kg in adults. AH the patients became aparasitemic within 72 hours. Excluding the results in one child who died on day 4, there was a 97% 28-day cure rate (99% in children and 92% in adults). Patients who had recrudes-cent infections used low doses of Artekin. Adverse effects, most commonly gastrointestinal complaints, were reported by 22 patients (21%) but did not necessitate premature withdrawal. 

The bisquinoline known as piperaquine (137) was synthesized in 1966 at the Shanghai Pharmaceutical Industry Research Institute. Piperaquine was found to be active against chloroquine-resistant falciparum malaria. In order to delay resistance, it is used in combination therapy, including with dihydroartemisinin, a derivative of the Chinese plant product artemisinin, first isolated in 1972. 

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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