Inhibition of Antimalarial Action of Sulfonamides by p-Amino-benzoic Acid

Abstract

It has been found that p-aminohenzoic acid prevents the inhibitory action of sulfanilamide on the growth of hemolytic streptococci in vitro 1 2 and in vivo. 3 This compound also inhibits the therapeutic effect of sulfanilamide on mice inoculated intracerebrally with the virus of lymphogranuloma venereum. 4 It has been suggested 2 3 4 that sulfanilamide exerts its action by competing for an enzyme associated with a metabolite similar in structure to p-aminobenzoic acid and essential to the organism.

Coggeshall 5 showed that sulfanilamide had a marked effect against plasmodia (Plasmodium knowlesi in rhesus monkeys). Other sulfonamides 6 were shown to be effective against P. knowlesi and against Plasmodium cynomolgi and Plasmodium inui in rhesus monkeys. Sulfadiazine was shown 7 to be effective against human malaria (Plasmodium vivax and Plasmodium falciparum). The present paper reports the effect of p-aminobenzoic acid in inhibiting the action of sulfanilamide against plasmodia.

Plasmodium gallinaceum was used as the test infection in Leghorn or Rhode Island Red chicks weighing 50-100 g. Five birds were used for each test and 10 for each control group. The drugs used were mixed with a powdered chick mash so that the stated daily dose of drug was contained in 10 g of mash. This amount of drug-food mixture was consumed over a 24-hour period. Blood concentrations of sulfanilamide, determined by the method of Marshall and Litchfield 8 with a photoelectric colorimeter, were shown to be maintained at a uniform level over a 24-hour period by this method of administration. Drug feeding was continued for 10 days with blood level determinations on the 2nd and 3rd days.