Disposition of 14C-acetohydroxamic acid and 14C-acetamide in the rat.
Acetohydroxamic acid (AHA) has been identified as a potential agent for the treatment of infection-induced staghorn renal calculi in patients. The pharmacokinetics and disposition of 14C-acetamide have been evaluated in rats following iv and oral administration. The results of these experiments suggest that, following oral administration to rats, AHA is absorbed very rapidly from the gastrointestinal tract and is metabolized to acetamide and CO2. Approximately 50-56% of the iv dose and 40-49% of the oral dose of 14C-AHA is excreted in the urine, suggesting a significant nonrenal elimination pathway for AHA and metabolite(s). This view is supported by the fact that a significant portion of the administered radioactivity (6-10%) is eliminated by the breath as 14CO2. Administration of 14C-acetamide to rats revealed that the compound is predominantly eliminated via the renal route, accounting for 68% of the administered radioactive dose. However, approximately 30% of the dose in the case of both AHA and acetamide could not be recovered, either in the urine or in the breath, during the 72-hr period of the experiment. This suggests that acetamide, either by direct administration or derived as a metabolite of AHA in the rat, may undergo further metabolism to get incorporated into the acetate pool. This would result in very slow elimination of the remaining activity as 14CO2 or as another unknown metabolite.