Concentration and time dependency of artemisinin efficacy against Plasmodium falciparum in vitro.
A chloroquine-sensitive strain of Plasmodium falciparum, F32, from Tanzania was exposed during continuous culture to concentrations of artemisinin, 10(-8)-10(-5) M, with exposure times ranging from 1 to 96 hr. After drug exposure, the cultures were washed and the incubation was continued for one or two parasite cycles to assess the remaining viability of the parasites. Artemisinin at a concentration of 10(-6) M inhibited parasite growth by 63% within 3 hr of drug exposure. The parasitemia then continued to decrease after removing the drug by washing the cultures. A 95% inhibition was thus observed 48 hr later. For 100% inhibition, at least 12 hr of exposure to 10(-6) M artemisinin was required. The compound at a concentration of 10(-7) M inhibited growth by 86% within 24 hr of drug exposure and by 98% 48 hours after removing the drug. A concentration of 3 x 10(-8) M exhibited 97-100% inhibition only after 72 or 96 hr of drug exposure, while 10(-8) M did not have any appreciable effect on the growth of the parasites even after 96 hr. It is concluded that artemisinin at high concentrations has a significant rapid in vitro effect that appears to be highly parasitocidal. The compound appears to have a broad spectrum of action, not only schizontocidal as reported earlier, but also against the asexual blood stages of P. falciparum.
Department of Biopharmaceutics and Pharmacokinetics, Biomedical Centre, Uppsala University, Sweden.
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D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D010963:Plasmodium falciparum / Q000187:drug effects*; D012717:Sesquiterpenes / Q000494:pharmacology*; D013997:Time Factors
D000962:Antimalarials; D037621:Artemisinins; D003470:Culture Media; D012717:Sesquiterpenes; C031327:artemisinin