The action of pteroyl glutamic acid and natural sources of folic acid on blood dyscrasias induced by sulfonamide drugs.

By H. G. PETERING, PH.D., R. A. DELOR, B.S., AND H. C. MURRAY, PH.D. F OLIC acid or vitamin B9 deficiency has been induced in the rat by feeding a purified diet containing succinyl sulfathiazole or sulfaguanidine)’2’3’4’5’6 This deficiency is corrected in either case by feeding free or conjugated pteroyl glutamic acid while the syndrome produced by sulfaguanidine is also corrected by paraaminobenzoic acid. The action of these drugs has been considered to be due to their inhibitory effect on the synthesis of folic acid in the intestinal tract of the animal.7 It has been known for some time that the more soluble sulfonamides widely used in medicine also cause blood dyscrasias in human patients which resemble those due to folic acid deficiency in rats fed sulfasuxidine or sulfaguanidine.8’ o Some work with experimental animals has shown that sulfanilamide, sulfathiazole, and sulfadiazine cause leukopenia, granulocytopenia, and even anemia, in addition to other toxic manifestations upon prolonged administration.11.11.hi Kornberg, Daft, and Sebrell’2 have reported that the dyscrasias in the rat due to soluble sulfonamide can be alleviated by treatment with Wilson liver fraction L and brewers’ yeast. The importance of the soluble sulfonamides in medical practice and the fact that some investigators consider that these drugs are retained in the intestinal tract in sufficient quantity to produce some bacteriostasis14’15’16 which might cause the appearance of folmc acid deficiency have prompted us to report our studies on the effect of crystalline folic acid, liver extract powder,’2#{176} yeast extract, and paraaminobenzoic acid in the prevention of blood dyscrasias induced by prolonged administration of sulfanilamide, sulfathiazole, and sulfadiazine. Chronic toxicity studies reported here were undertaken, since some investigators believe they are more applicable to medical therapeutics than are acute toxicity studies.17