Succinyl Sulfathiazole,a New Bacteriostatic Agent Locally Active in the Gastrointestinal Tract

Abstract

Much interest has been aroused during the past year over the prospect of developing therapeutic agents that have antibacterial activity in the bowel. 1 , 2 , 3 A study covering 20 sulfonamides has unearthed a compound of considerable promise.

Succinyl sulfathiazole.∗ COOH . CH₂ . CH₂. CO . NH . C₆H₄ .-SO₂. NH . C₃H₂NS, has been shown to have little toxicity when administered to dogs orally at 4-hour intervals day and night. A dosage of one gram per kilo daily given in 6 equal doses results in a fecal drug content of from 5 to 10%. Under this regimen approximately 5% of the ingested drug is excreted in the urine, and the concentration of the drug in the blood will average 1.5 mg % of sulfathiazole and 2.0 mg % of succinyl sulfathiazole. The sulfathiazole is formed by the hydrolysis of a small portion of the conjugated compound by the animal tissues and by the bacteria in the bowel. Crystals of the drug do not appear in the urine.

The antibacterial action of succinyl sulfathiazole in the bowel as measured by the effect on the coliform organisms is presented graphically. The drug given in therapeutic doses profoundly alters the feces. They become semifluid and practically odorless.

No toxic manifestations have been observed. The animals gain weight and show no gross or microscopic evidence of tissue damage after receiving one gram per kilo of the compound daily in 6 doses for 5 weeks. During this entire period the number of B. coli per gram of wet stool averaged less than 100 organisms as compared to an average normal flora of 10,000,000.

Succinyl sulfathiazole has been administered to 40 human beings with various organic lesions and acute intestinal infections without the production of toxic reactions.