Observations on the Inhibition of Sulfonamide Action by Para-aminobenzoic Acid.

Considerable interest has been aroused recently in the investigation of substances which inhibit the action of the sulfonamide drugs. Lockwood (1) showed that peptones inhibit the action of sulfanilamide on streptococci. Stamp (2) isolated certain fractions of streptococci, and Green (3) isolated fractions of brucella, which have similar activity with respect to the corresponding organisms. West and Coburn (4) showed that under certain conditions coenzymes inhibit the action of sulfapyridine on staphylococci. MacLeod (5) found that the action of sulfapyridine on the colon bacillus in a synthetic medium can be nullified by extracts of certain animal tissues. Woods (6) extracted fractions of yeast which were capable of overcoming the bacteriostatic action of sulfanilamide on streptococci and on colon bacilli. From an analysis of the properties of the active extracts he was led to test a series of known chemical compounds and found that para-aminobenzoic acid had marked inhibitory properties in vitro. Selbie (7) supplemented this work by demonstrating that mice infected with streptococci could not be saved by sulfanilamide if para-aminobenzoic acid were administered at the same time. The reports of the two last named authors and the discussion of their work by Fildes (8) led us to undertake studies of some of the properties of para-aminobenzoic acid in vitro and in human subjects. In this paper are reported the results of observations on the following aspects of these studies: (1) the quantitative relationship between the bacteriostatic effect of sulfonamides on the pneumococcus and the inhibition of this effect by para-aminobenzoic acid; (2) the stages of the action of sulfapyridine on the pneumococcus during which inhibition by para-aminobenzoic acid is effective; (3) a consideration of the absorption and excretion of para-aminobenzoic acid and its chemical determination in blood and urine; (4) a comparison of the activity of the urine of human subjects following ingestion of para-aminobenzoic acid with the activity of this drug when added in vitro to normal urine (the bacteriostatic effect of sulfathiazole on the colon bacillus was utilized for this purpose); (5) a study of the effect of oral administration of para-aminobenzoic acid on the bactericidal power of the blood of subjects receiving sulfonamides; and (6) the effect of paraaminobenzoic acid on rashes and fever due to sulfonamide toxicity.