Interactions of atovaquone with other antimalarial drugs against Plasmodium falciparum in vitro.

A series of Plasmodium falciparum in vitro drug sensitivity studies were conducted in order to evaluate atovaquone in combination with other antimalarial drugs and thus to identify a potential partner for a fixed combination. The derived isobolograms indicated that drug interactions ranged from antagonism through addition to synergy. Of particular note were the quinolines and artemisinin analogues, which were all antagonistic, and the biguanides and tetracycline, which showed synergy. Proguanil emerged as the most promising of the current antimalarials as a partner for atovaquone in a fixed combination, with tetracycline as back-up.