The activity of triple combinations of antifolate biguanides, with and without folinic acid, against plasmodium falciparum in vitro.

At least two triple combinations of biguanides, proguanil-atovaquone-dapsone and PS-15-atovaquone-dapsone, may be useful in treating drug-resistant infections of falciparum malaria. Each of these triple combinations can be considered as two synergistic combinations: proguanil-atovaquone and cycloguanil-dapsone, and PS-15-atovaquone and WR99210-dapsone, respectively. Since folinic acid might mitigate the possible side-effects produced by such drug combinations, both combinations were administered, with and without folinic acid, to 16 Saimiri sciureus monkeys. The antimalarial activity in serum samples collected from each monkey, 3, 6 and 24 h after drug administration, was then determined in vitro, against Plasmodium falciparum. The addition of folinic acid had no apparent affect on the antimalarial activity of the triple combinations tested. Such combinations may be useful against Pneumocystis carinii and Toxoplasma gondii in immunocompromised patients, as well as against malaria.