Variability of the in vitro activity of proguanil and cycloguanil on the erytrocyte stages of Plasmodium falciparum according to conditions of culture

The in vitro activity of proguanil, cycloguanil (active metabolite of progu anil), pyrimethamine, and chloroquine was determined for 14 isolates of Pla smodium falciparum and he chloroquine-resistant W2 clone. In vitro assays w ere performed by using different types of RPMI 1640 culture medium and incu bation period. The use of he standard RPMI medium or RPMI medium containing low concentrations of folate and para-aminobenzoic acid increases the 50% inhibitory concentrations of cycloguanil and pyrimethamine, as compared wit h he use of folate- and para-aminobenzoic acid-free RPMI medium. The concen trations of folate and para-aminobenzoic acid did not affect he in vitro ac tivity of proguanil and chloroquine. However prolongation of the incubation period from 42 to 66 hours decreased the 50% inhibitory concentrations of all test compounds. The weak antagonism in vitro between chloroquine and pr oguanil or cycloguanil does not seem to have any repercussion on the in viv o efficacy of chloroquine-proguanil combination.