PHYSIOLOGIC DISPOSITION OF SHORT CHAIN ALIPHATIC HYDROXAMATES IN THE MOUSE. I. THE ONE-THROUGH-FOUR CARBON HYDROXAMATES: EXCRETION AND CONVERSION TO AMIDES

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

The excretion and metabolism of four homologous hydroxamic acids in mice has been studied, with acetohydroxamate as the index compound. Urinary excretion of these compounds was very rapid, yet incomplete. In the case of acetohydroxamate more than 90% of the total amount excreted was present in the first 8-hour urine collection, yet only 65 to 70% of the administered dose was recovered in 48-hour urine specimens. The urinary percent recovery of acetohydroxamate was constant over a 5-fold dose range (160-800 mg/kg b.w.), and was also unaffected by pretreatment of the animals with barbital or 3-methylcholanthrene. Urinary recovery of the congeneric compounds was much lower: 24% for formohydroxamate, 34% for propionohydroxamate and 35% for isobutyrohydroxamate. Evidence for the appearance in the urine of the corresponding amide to each of the administered hydroxamates was obtained by paper or thin-layer chromatography. In the case of acetohydroxamate, urinary acetamide accounted for 10 to 20% of the administered dose and was therefore a major metabolite. In the case of the other compounds, however, the amide recovery was much lower, and more than half the administered dose remained unaccounted for in this study. The use of isotopically labeled hydroxamates would appear to be essential in the further study of the physiologic disposition of these compounds.