Author/Editor     Janse, CJ; Waters, AP; Kos, J; Lugt, CB
Title     Comparison of in vivo and in vitro antimalarial activity of artemisinin, dihydroartemisinin and sodium artesunate in the Plasmodium berghei-rodent model
Type     članek
Source     Int J Parasitol
Vol. and No.     Letnik 24, št. 4
Publication year     1994
Volume     str. 589-94
Language     eng
Abstract     The in vitro and in vivo antimalarial activity of artemisinin, artesunate and dihydroartemisinin has been compared using the Plasmodium berghei-rodent model. Drugs were added to synchronized short-term in vitro cultures of the erythrocytic stages and inhibition of parasite development was determined by measuring DNA synthesis by flow cytometry. Dihydroartemisinin was the most effective drug. IC50 values of artemisinin, artesunate and dihydroartemisinin were 1.9, 1.1 and 0.3 x 10(-8) M, respectively, when drugs were present during the complete 24 h developmental cycle. IC50 values increased significantly when drugs were added to old trophozoites, indicating that the older stages are less sensitive. To determine the in vivo antimalarial activity, mice with a parasitaemia between 1 percent and 3 percent were injected intramuscularly on 3 consecutive days with a single dose of the drugs dissolved in Miglyol 812. Again dihydroartemisinin was the most effective drug in vivo, showing a cure rate of 47 percent at 10 mg/kg bodyweight, while with both other drugs the recrudescence rate was 100 percent at the same dosage. This study showed that the P. berghei-rodent model is a useful tool for accurate comparisons of the in vivo and in vitro antimalarial activity of drugs.
Descriptors     ANTIMALARIALS
MALARIA
PLASMODIUM BERGHEI
SESQUITERPENES
ANTIMALARIALS
MICE
RATS
RATS, WISTAR
SESQUITERPENES