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  • Title: The activity of proguanil and its metabolites, cycloguanil and p-chlorophenylbiguanide, against Plasmodium falciparum in vitro.
    Author: Watkins WM, Sixsmith DG, Chulay JD.
    Journal: Ann Trop Med Parasitol; 1984 Jun; 78(3):273-8. PubMed ID: 6385887.
    Abstract:
    Using an in vitro radioisotopic method, the activity was measured of proguanil, its metabolites cycloguanil and p-chlorophenylbiguanide (PBG), pyrimethamine, and chloroquine against seven Kenyan and three South East Asian strains of Plasmodium falciparum. Five Kenyan isolates were sensitive to both pyrimethamine and cycloguanil in vitro, while the Smith and two Kenyan strains were resistant to both these drugs. Cross-resistance was incomplete: the Camp strain was resistant to pyrimethamine but not cycloguanil, and the FVO strain was resistant to cycloguanil but not pyrimethamine. Both proguanil and PBG exhibited weak antimalarial activity in vitro, but inhibitory blood levels of either compound are unlikely to occur after a normal human dose of proguanil. The results indicate that the activity of proguanil against P. falciparum is due entirely to the action of its active metabolite cycloguanil.
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