The activity of drug combinations against established infections of rodent malaria

Abstract

SUMMARYIn the experiments reported here treatment (with a single dose or daily for 4 days) was delayed until 3 days after inoculation. Various combinations of M&B 35769, 2:4-diamino-5-[3(4–4′-chlorophenylphenoxy)propyl-l-oxy]-6-methylpyrimidine HC1, plus sulphadoxine, and of M&B 35769 plus dapsone, were examined and it was concluded that no universally ideal ratio of constituents in a combination is possible because the optimum ratio depends upon the activity of the constituents on their own and therefore varies from strain to strain. Activity was assessed on the 24th day after infection. M&B 35769 was markedly superior to pyrimethamine against all strains when the compounds were given on their own but, although it showed good potentiation with sulphadoxine and dapsone, much of its lead over pyrimethamine was lost in combination. M&B 36821 2–4-diamino-5-[3-(3,4′-dibromobiphenyl-4-oxy)-propyl-l-oxy]-6-methyl pyrimidine HC1, was more active than M&B 35769 against pyrimethamine- and cycloguanil-resistant strains but not against sensitive strains.