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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.