3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE INHIBITORS LOVASTATINAND SIMVASTATIN INHIBIT IN-VITRO DEVELOPMENT OF PLASMODIUM-FALCIPARUMAND BABESIA-DIVERGENS IN HUMAN ERYTHROCYTES

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors lovasta tin and simvastatin inhibit the in vitro intraerythrocytic development of Plasmodium falciparum and Babesia divergens, with concentrations i nhibiting parasite growth by 50% in the ranges of 10 to 20 and 5 to 10 mu g.ml(-1), respectively. For P. falciparum, the 50% inhibitory conc entrations were in the same range whatever the chloroquine susceptibil ity of the strains tested (strain F32/Tanzania [chloroquine susceptibl e] or FcB.1/Columbia [resistant]), The stage-dependent susceptibility of P. falciparum to simvastatin was studied by subjecting synchronized cultures to 6-h pulses of drug throughout the 48-h erythrocytic life cycle. The most important inhibitory effects were observed between the 12th and 30th hours of the cycle, corresponding to the trophozoite st age. This period precedes the S phase and the nuclear divisions. Paras ites in the newly formed ring stage (time zero to the 6th hour of the cycle) and the schizont stage (30th to 48th hour of the cycle) were we akly or not susceptible to simvastatin pulses.