PHYSIOLOGIC DISPOSITION OF SHORT CHAIN ALIPHATIC HYDROXAMATES IN THE MOUSE. II. ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF 1-¹⁴C-ACETOHYDROXAMIC ACID

¹ Biochemistry Branch, Armed Forces Institute of Pathology, Washington, D.C.

The disposition of carboxyl-¹⁴C-acetohydroxamic acid was evaluated in mice by comparison with ¹⁴C-urea, by using radioisotopic, spectrophotometric and chromatographic assays. Acetohydroxamate was absorbed about half as fast as urea, giving peak blood levels at one hour and had an approximate biologic half-life of four hours, about 3 times that of urea. Approximate drug space was 71% of body weight, suggesting that the compound was distributed throughout total body water. Within 24 hours, about 60% of the administered dose was excreted unchanged in the urine, 15 to 20% was excreted in the urine as acetamide and 10% was excreted as acetate, identified by dual isotope analysis. Another 7% was expired as carbon dioxide, presumably derived from acetate, while about 2% remained in the blood and tissues with rather uniform distribution and only 1% appeared in the feces. The kinetic pattern of urinary excretion of acetate and acetamide suggested that the acetate was derived directly from the acetohydroxamate and not secondarily from the acetamide.

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