THE EFFECT OF ATOVAQUONE (566C80) ON THE MATURATION AND VIABILITY OF PLASMODIUM-FALCIPARUM GAMETOCYTES IN-VITRO

Atovaquone (566C80), a hydroxynaphthoquinone, was investigated for act ivity against Plasmodium falciparum gametocytes (NF54 strain) in vitro . After 96 h of continuous exposure to the drug at 1.4x10(-7)M (a conc entration achievable in humans 14 d after administration of a therapeu tic dose of 10 mg/kg) reductions of 75%, 54% and 20% in the number of gametocyte stages 2, 3 and 4, respectively, were achieved. A small inc rease (14%) in stage 5 gametocytes was seen. Ar the same concentration , atovaquone showed greater activity against the asexual stages of P. falciparum, reductions of 93%, 96% and 43% in the number of rings, sch izonts and trophozoites, respectively, being achieved. These data are consistent with inhibition of maturation of trophozoites. The observed effect on maturation of gametocytes is similarly consistent with bloc kade of gametocyte recruitment from merozoites produced by the precedi ng schizogony, or to stasis of intraerythrocytic sexual development be fore the formation of stage 2 gametocytes.