Artesunate comparative studies

Barnes KI et al Efficacy of rectal artesunate compared with parenteral quinine in initial treatment of moderately severe malaria in African children and adults A randomised study. Lancet 2004 363 1598. [PMID 15145633]... 

Deoxoartemisinin and carboxypropyldeoxoartimisinin have also been shown to have anti-tumour activity and, NMR studies on solution conformations have been reported <00BBR359>. One of the problems with artemisinin use is its poor water solubility characteristics. An attempt to rectify this, and to overcome stability problems associated with sodium artesunate in solution, has involved the introduction of amino group functionality as in 127 (eg. R = 0(CH2)3NR r2 where NR r2 = morpholine). The maleate salt of this compound has reasonable water solubility and aqueous solutions are stable at room temperature for an extended time. However activity against Plasmodium knowlesi in rhesus monkeys after oral administration was poorer compared with artesunic acid <00JMC1635>. 

Artemisinin-based regimens are often regarded as safe and effective drugs in the recent years however, clinically relevant artemisinin resistance has been reported both from laboratory and field studies. Some of these studies have shown that P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thailand. This resistance was characterized by a slow parasite clearance in vivo, without corresponding reductions on conventional in vitro susceptibility testing.Although this resistance to artemisinin is still very mild and limited, its emergence would be disastrous because of the lack of alternative treatments. 

Comparative safety and activity study with FQ/Artesunate vs. Amodiaquine/ Artesunate in African adult patients. 

In the South East Asian Quinine Artesunate Malaria Trials (SEQUAMAT), a multicenter, randomized, open study in 1461 patients (including 202 children) artesunate was associated with a 35% reduction in the risk of mortahty compared with quinine [10. Artesunate has therefore been recommended by the WHO as the treatment of choice for severe and complicated malaria in low transmission areas and in the second and third trimester of pregnancy. 

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