Detoxication of a Substituted Phenyl Stibonate in the Rat by Administration of p -Aminobenzoic Acid

Abstract

The writer has reported 1 experiments that demonstrated the highly protective powers of p-aminobenzoic acid when administered in substantial but well tolerated quantities to rats that simultaneously had received high lethal doses of Carbarsone, “Tryparsamide,” arsan-ilic acid, and Acetarsone. Further experiments, to be published in extenso elsewhere, have shown that p-aminobenzoic acid provides equally high protection against other penta-valent arsenicals including phenyl arsonic acid and also against at least one of the trivalent arsenical antisyphilis drugs.

In view of the therapeutic value placed upon some of the less toxic antimony compounds in the treatment of such important tropical diseases as kala-azar and schistosomiasis, it seems desirable to record the capacity of p-aminobenzoic acid to protect rats against acute fatal doses of the German proprietary drug, “Stibosan” (sodium m-chloro p-acetyl amino phenyl stibonate), the only pentavalent antimony compound which was presently available for test purposes in our laboratory.

The test animals were albino rats, weighing approximately 100 g but otherwise unselected as to breed, sex, or age. Treated and control animals were maintained on a balanced diet in large communal cages. p-Aminobenzoic acid in the form of its water-soluble sodium salt was administered either by mouth or parenterally at the same time as the antimonial drug was introduced into the saphenous vein of the rat.

In the early stages of these studies, we administered a so-called sustaining dose of p-aminobenzoic acid for the following 2 or 3 days. Experiments already completed have indicated that the quantity of p-aminobenzoic acid administered has usually been more than was necessary to achieve the desired effect. A typical experiment is summarized in Table I.

Discussion. As tested in our laboratory against Trypanosoma equiperdum in rats, “Stibosan” has proved to have a very definite but relatively low therapeutic index. The quantity of drug necessary to effect a permanent cure of rats infected with T. equiperdum approaches the maximum dose that the majority of rats can tolerate.