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Int J Parasitol. 1996 May;26(5):519-25.

In vitro stage-specific sensitivity of Plasmodium falciparum to quinine and artemisinin drugs.

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University of Western Australia, Department of Medicine, Fremantle Hospital, Australia.


The inhibitory effects of quinine, chloroquine and 4 qinghaosu drugs, artemisinin, artemether, artesunate and dihydroartemisinin, on 4 culture-adapted isolates and 2 standard clones of Plasmodium falciparum were determined in vitro. All isolates were sensitive to the widely used antimalarial drugs quinine (EC50 range 3 x 10(-8)-1 x 10(-7) mol/L) and chloroquine (EC50 range 1 x 10(-9)-7 x 10(-9) mol/L), irrespective of the geographical origin or treatment history of the patients from which they were taken. In general, the qinghaosu drugs were more potent than the conventional antimalarials, having EC50 values of 3 x 10(-11)-3 x 10(-8) mol/L. Stage-specific data indicated that quinine has a primary mode of action on mature parasite forms, achieving 80-100% growth inhibition within 2-4 h of drug exposure. The stage-specific activity of the 3 qinghaosu drugs artemisinin, artemether and dihydroartemisinin differed from that of quinine, and each derivative displayed a unique stage-specific profile. Artemisinin was rapidly effective against both rings and schizonts, achieving 100% growth inhibition within 6-8 h. The inhibitory effects of artemether were less rapid, requiring 10 h to achieve 70-80% ring stage growth inhibition. Dihydroartemisinin was highly effective against all parasite stages in most cases achieving 100% growth inhibition within 2-4 h of exposure. The results confirm that the qinghaosu drugs are potent antimalarials, and suggest different stage-specific profiles compared to conventional antimalarial drugs.

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