Artesunate is a water soluble hemisuccinate ester of artemisinin, the main antimalarial principle isolated from Artemisia annua L. It is a fast-acting schizontocide of both falciparum and vivax malaria. Artesunate was shown to induce shorter parasite clearance times than chloroquine, mefloquine or quinine and more rapid symptomatic response. It is effective against multiresistant infections including cases of complicated and cerebral malaria. However, following artesunate monotherapy- in particular when given over less than 5 days- recrudescences may occur. Therefore, the course of artesunate therapy should be completed by another antimalarial such as mefloquine.

Artemisinin and its derivatives are hydrolysed rapidly in vivo to dihydroartemisinin ( dihydroqinghaosu) . This active metabolite may be eliminated more slowly than the parent compounds. In plasma, about 75% of the drug is protein-bound. In volunteer studies, intravenous artesunate is cleared very rapidly by biotransformation to dihydroartemisinin, which is eliminated with a half-life of 45 min. Oral artesunate is probably hydrolysed completely before it enters the systemic circulation.. Animal studies indicate extensive first-pass metabolism of artemisinin. Pharmacokinetics of intravenous and intramuscular artesunate in patients with severe falciparum malaria were performed recently in Vietnamese patients. The plasma concentrations of artesunate and dihydroartemisinin were analysed by HPLC-EC(reductive mode) Cmax of artesunate and dihydroartemisinin were 510 and 390ng/ml respectively. At 90 min, artesunate and dihydroartemisinin were still detected at the concentration of 110ng/ml and 200ng/ml, respectively. The half life of bio-transformation was rapid i.e 0.06h with elimination half-life of 30 min. With intravenous administration, Cmax was higher than with intramuscular administration (2640 ng/ml for artesunate and 2020 ng/ml for dihydroartemisinin). However, at 90 min, artesunate was no longer detected in plasma but dihydroartemisinin could still be seen at 190 ng/ml (a concentration similar to that observed with theintramuscular injection)

Oral treatment of non-complicated P. falciparum malaria   in cases resistant to other antimalarials including mefloquine. Rectal treatment of complicated and cerebral P. falciparum malaria, especially in unconscious patients. GSUNATE is not recommended for the prophylaxis of malaria.

As the experience in pregnant patients is limited and as embryotoxicity was seen in pregnant rats following s.c.injections, GSUNATE should not be administered during the first trimester of pregnancy unless the treatment is considered life-saving as e.g. in cerebral malaria. Also, no trials have been carried out in pregnant or lactating women.

There have been over twenty combined clinical studies with artesunate given both parenterally, orally and rectally with no reports of local or systemic toxicity. No significant adverse side effect have been observed in more than 2000 malaria patients, reported in published studies, treated with related compounds. However, laboratory findings occasionally showed transient reduction in reticulocytes and neutrophil granulocytes, especially the young forms, but there were no symptoms or signs of super imposed infections. Transient increase in transaminase has been reported.