Concentration and time dependency of artemisinin efficacy against Plasmodium falciparum in vitro. 1994

M H Alin, and A Bjorkman
Department of Biopharmaceutics and Pharmacokinetics, Biomedical Centre, Uppsala University, Sweden.

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.

UI MeSH Term Description Entries
D010963 Plasmodium falciparum A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics. Plasmodium falciparums,falciparums, Plasmodium
D003470 Culture Media Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN. Media, Culture
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000962 Antimalarials Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) Anti-Malarial,Antimalarial,Antimalarial Agent,Antimalarial Drug,Anti-Malarials,Antimalarial Agents,Antimalarial Drugs,Agent, Antimalarial,Agents, Antimalarial,Anti Malarial,Anti Malarials,Drug, Antimalarial,Drugs, Antimalarial
D012717 Sesquiterpenes Fifteen-carbon compounds formed from three isoprenoid units with general formula C15H24. Farnesanes,Farnesene,Farnesenes,Sesquiterpene,Sesquiterpene Derivatives,Sesquiterpenoid,Sesquiterpenoids,Derivatives, Sesquiterpene
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D037621 Artemisinins A group of SESQUITERPENES and their analogs that contain a peroxide group (PEROXIDES) within an oxepin ring (OXEPINS).

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