MALARONE PAEDIATRIC Film-coated tablet Ref.[51433] Active ingredients: Atovaquone Proguanil Proguanil and Atovaquone

Atovaquone is a selective and potent inhibitor of the eukaryotic mitochondrial electron transport chain in a number of parasitic protozoa and the parasitic fungus P. jiroveci. The site of action appears to be the cytochrome bc1 complex (complex III).

Proguanil is an antimalarial drug and dihydrofolate reductase inhibitor. It acts like the other antifolate antimalarials by interfering with the folic-folinic acid systems and thus exerts its effect mainly at the time the nucleus is dividing. Proguanil is effective against the exoerythrocytic forms of some strains of plasmodium falciparum but it has little or no activity against the exoerythrocytic forms of p. Vivax.

Atovaquone and proguanil interfere with two different pathways involved in the biosynthesis of pyrimidines required for nucleic acid replication. The mechanism of action of atovaquone against P. falciparum is via inhibition of mitochondrial electron transport, and collapse of mitochondrial membrane potential. One mechanism of action of proguanil, via its metabolite cycloguanil, is inhibition of dihydrofolate reductase, which disrupts deoxythymidylate synthesis. Proguanil also has antimalarial and is able to potentiate the ability of atovaquone to collapse mitochondrial membrane potential in malaria parasites. This latter mechanism may explain the synergy seen when atovaquone and proguanil are used in combination.