The activity of drug combinations against established infections of rodent malaria.
In 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 35,769, 2:4-diamino-5-[3(4-4'-chlorophenylphenoxy)propyl-1-oxy]-6-methylpy rimidine HCl, plus sulphadoxine, and of M&B 35,769 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 35,769 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 36,821 2-4-diamino-5-[3-(3,4'-dibromobiphenyl-4-oxy)-propyl-1-oxy]-6-meth yl pyrimidine HCl, was more active than M&B 35,769 against pyrimethamine- and cycloguanil-resistant strains but not against sensitive strains.
Hill
J
J
Research Laboratories, May & Baker Ltd, Dagenham, Essex.
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000627:therapeutic use; D002738:Chloroquine / Q000627:therapeutic use; D003622:Dapsone / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D010962:Plasmodium berghei; D010967:Plasmodium yoelii; D011739:Pyrimethamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D013413:Sulfadoxine / Q000008:administration & dosage / Q000627:therapeutic use
D000962:Antimalarials; C043001:M&B 35769; C053774:M&B 36821; D013413:Sulfadoxine; D002738:Chloroquine; D003622:Dapsone; D011739:Pyrimethamine