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-d apsone and PS-15-atovaquone-dapsone, map be useful in treating drug-re sistant infections of falciparum malaria. Each of these triple combina tions can be considered as two synergistic combinations: proguanil-ato vaquone and cycloguanil-dapsone, and PS-15-atovaquone and WR99210-daps one, respectively. Since folinic acid might mitigate the possible side -effects produced by such drug combinations, both combinations were ad ministered, with and without folinic acid, to 16 Saimiri sciureus monk eys. The antimalarial activity in serum samples collected from each mo nkey, 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 combina tions tested. Such combinations mag be useful against Pneumocystis car inii and Toxoplasma gondii in immunocompromised patients, as well as a gainst malaria.