Concentration and Time Dependency of Artemisinin Efficacy Against Plasmodium falciparum in Vitro

M. Hassan AlinDepartment of Biopharmaceutics and Pharmacokinetics, Biomedical Centre, Uppsala University, Department of Infectious Diseases, Huddinge University Hospital, Uppsala, Sweden

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A. BjorkmanDepartment of Biopharmaceutics and Pharmacokinetics, Biomedical Centre, Uppsala University, Department of Infectious Diseases, Huddinge University Hospital, Uppsala, Sweden

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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 × 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.

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