Atovaquone antimalarial activity

The mechanism of the antimalarial activity of proguanil or chlorproguanil is unknown. Proguanil as the biguanide accentuates the mitochondrial membrane-potential-collapsing action of ato-vaquone against P. falciparum but displays no such activity by itself (see Atovaquone, above). 

In contrast to cycloguanil, resistance to the intrinsic antimalarial activity of proguanil itself, either alone or in combination with atovaquone, has yet to be documented. 

An in vitro study found that doxycycline potentiated the antimalarial activity of atovaquone, but there appears to be no information on the effect of doxycycline on the absorption of atovaquone. A study looking at the population pharmacokinetics of atovaquone in 24 Thai patients found that neither the oral clearance nor the volume of distribution of atovaquone were significantly affected by the concurrent use of tetracycline. ... 

FIGURE 39-2 Spectrum of clinically useful activity for antimalarial drugs. For atovaquone and proguanil, reliable activity against the primary liver stage has been shown for P. falciparum only for the class 1 agents, activity against... 

Beitani et al. [100] also showed that SkD was inactive against heme biomineralization process and did not affect permeability pathways induced by a parasite in the host erythrocyte membrane. They also showed that SkD enhanced the activity of atovaquone on Plasmodium mitochondrial membrane potential, while it had an additive effect when combined with other commercial antimalarials. 

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