Artemether is the most active derivate of the Artemesinines a new class of antimalaria drugs derived from Artemisinin. The latter compound is extracted from the plant Artemisia Annua and Artemether is prepared semi-synthetically. Lumenfantrine is a synthetic aryl amino alcohol similar to mefloquine and hal-fantrine.
PHARMACOLOGICAL PROPERTIES:
Pharmacodynamics:
Both components of BG MAL–560 have their own action sites in the malaria parasite. The presence of the perioxide bridge in Artemether (generating single oxygen and free radicals: those are very cytotoxic to the plasmodia) appears to be essential for antimalaria activity. Morphological changes of the parasitic membranes induced by Artemether have been described, being the result of free-radical action.
Lumefantrine interferes more in plymerization processes. Other in vitro test suggest that both cause a marked diminution of nucleic acid synthesis. Inhibition of protein synthesis as the basic mechanism of action is suggested in studies which showed morphological changes in ribosomes as well as in the endoplasmic reticulum. Although Artemether acts essential as a blood schizonticide, BG MAL-560 did clear gametocytes in pmparative clinical trials. Orally administered Artemether is rapidly absorbed reaching therapeutic levels within 60-90 minutes.
Artemether is metabolized in the liver to the demethylated derivate dihydroartemisinin (DHA). The elimination is rapid, with a T½ of 2-4 hours. Dihydroartemisinin, being a potent antimalaria itself, has a T½ of about 2-4 hours. The degree of binding to plasma proteins in man is about 50%. Radioactivity distribution of Artemether was found to be equal between cells and plasma.
The absorption of Lumefantrine is highly influenced by lipids and food intake (from 10% by fasten to 100% at normal diet). Therefore parents should be encouraged to give the medication with some fatty food as soon as it can be tolerated. Lumenfantrine is N-debutylated in human livermicrosomes. This metabolite has 5 to 8 fold higher antiparasitic effects than lumefantrine. Lumefantrine is found to be highly protein bound (95%). The elimination half life in malaria attaint patients will be 4 to 6 days. Lumefantrine and his metabolities are found in bile and faeces.
