Synthesis and Metabolism of Labeled Acetohydroxamic Acid,a Urease Inhibitor 1

Abstract

Summary

¹⁴C- and ³H-labeled acetohydroxamic acid were synthesized and purified by preparative thin-layer chromatography. When these compounds were given simultaneously to dogs, the ³H/¹⁴C ratio remained constant in urine, indicating that the ³H label was stable in vivo. In dogs, AHA was rapidly absorbed when given orally; when given by this route or intravenously, 80 to 90% of the administered radioactivity was recovered in the urine in 24 hr, predominantly as unmetabolized AHA. AHA was given by mouth to patients with cirrhosis and encephalopathy: radioactivity appeared promptly in the blood and urine and decreased exponentially. Urinary excretion was slower than in dogs, probably because of concomitant impairment of renal function. Less than 10% of urinary radioactivity was present as acetamide in dogs or patients. AHA was not excreted in the feces during the duration of the experiment. Side-effects of AHA given to patients included gastrointestinal symptoms and transient decrease of the blood platelet count.