Acetohydroxamic acid. Potential use in urinary infection caused by urea-splitting bacteria

• Published in: Urology (Ridgewood, N.J.) Vol. 5; no. 3; p. 299
• Main Authors: Griffith, D P, Musher, D M
• Format: Journal Article
• Language: English
• Published: United States 01-03-1975
• Subjects: Acetamides - metabolism; Administration, Oral; Animals; Bacteria - enzymology; Binding Sites; Chemical Phenomena; Chemistry; Dogs; Enzyme Inhibitors; Humans; Hydroxamic Acids - metabolism; Hydroxamic Acids - pharmacology; Hydroxamic Acids - therapeutic use; Hydroxamic Acids - toxicity; Injections, Intraperitoneal; Intestine, Small - metabolism; Liver Cirrhosis - drug therapy; Mice; Thymidine - metabolism; Thymus Gland - metabolism; Time Factors; Urease - antagonists & inhibitors; Urinary Calculi - drug therapy; Urinary Calculi - prevention & control; Urinary Tract Infections - drug therapy
• ISSN: 0090-4295
• DOI: 10.1016/0090-4295(75)90142-9

Several lines of evidence suggest that bacterial urease is the primary cause of infection-induced urinary stones. The hydroxamate group of compounds are specific urease inhibitors. Of the cogeners studied, to dat, AHA (acetohydroxamic acid) appears to have the most pharmacologic potential. AHA is rapidly and completely absorbed from the gastrointestinal tract and is concentrated and excreted in the urine. In animals it appears to be relatively nontoxic. Although its toxicity in human beings has not been studied, its similarity to hydroxyurea suggests that reversible toxicity involving the gastrointestinal tract and the hematopoietic systems may result when high doses are administered. The only known metabolite of AHA is acetamide which is nontoxic and rapidly excreted in the urine. Pharmacologic use of AHA is expected to be practical and relatively safe. Use of AHA in patients with urinary infections caused by urea-splitting bacteria may reduce pathogenicity of the infecting organism and may lead to prevention and/or dissolution of stones commonly associated with such infections.