Artemisinin-lumefantrine

Artemisinin combinations In a retrospective study of 46 adults in Cote D Ivoire who were given a 3-day regimen of combinations with artemisinin (lumefantrine, n=20 amo-diaquine, n = I3 mefloquine, n = 7 and piperaquine + trimethoprim, n = 6) and who developed hepatorenal failure, 12 died and 34 recovered within a median of 3-12 days after withdrawal of the combination therapy [IH]. In a comparison of variables between those who died and those who survived. 

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. 

The other natural compound and its derivatives that are now being widely constituted into anti-malarial drugs is artemisinin. This compound was isolated from the age-old Chinese anti-malarial drug, qinq hao su, isolated from the plant qinq hao or Artemisia annua, which is now a widely grown crop in Kenya and East Africa in general. Artemisinin is an excellent anti-plasmodial whose derivatives are now being constituted as artemisinin combination therapy drugs (ACTs) by different companies. An example of an ACT is Coartem, a combination of artemether and lumefantrine, from Novartis. 

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. 

Sidhu, A. B., Uhlemann, A. C., Valderramos, S. G., Valderramos, J. C., Krishna, S., and Fidock, D. A. (2006). Decreasing PfMDRl copy number in Plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and artemisinin. ]. Infect. Dis. 194,528-535. 

Artemisinin derivatives (artemisinin, artemether/lumefantrine - S% of patients had an asymptomatic prolongation of QTc intervals by greater than 30 milliseconds, with an actual QTc of greater than 450 milliseconds in males and greater than 470 milliseconds in females) Levofloxacin (rare case reports of torsade de pointes)... 

A series of artemisinin-based semisynthetic antimalarial derivatives, with all of them maintaining the key endoperoxide bridge, such as arteether (18), artemether (19), artesunate (20), and dihydroartemisinin (21), have been designed to improve the water solubility and the metabolic stability of artemisinin [53, 54], Among them, dihydroartemisinin (artenimol), is considered as a common active metaboUte of artemisinin derivatives [53, 54]. Currently, artemisinin-based therapies eombined with standard antimalarials such as amodiaquine, sulfadoxine-pyrimethamine, mefloquine, and lumefantrine are recommended by the World Health Organization (WHO) as first-line therapies for malaria [55, 56]. 

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