A study of the absorption, excretion, metabolism, and residues in tissues in rats fed carbon-14-labeled sulfamethazine

Sprague-Dawley male and female rats received medicated feeds containing 10, 40, 160, 640, 1280, and 2560 ppm of (phenyl-U-/sup 14/C)sulfamethazine for 7 days. Urinary radioactivity accounted for 51-68% of the dose in females and 31-45% in males. Sulfamethazine and N/sup 4/-acetylsulfamethazine accounted for 76-84% of the radioactivity in females and 22-63% in males. The N/sup 4/-glucose conjugate of sulfamethazine and two other sulfamethazine conjugates, on average, accounted for 73% of the urinary metabolites in males at drug levels below 640 ppm. At drug levels above 640 ppm, the concentration of these conjugates decreased in urine to suggest that there was a saturable process(es) in the male. Females also exhibited consistently high /sup 14/C residues in tissues and blood to further indicate there were apparent sex-related differences in the metabolism of sulfamethazine in rats. Sulfamethazine and N/sup 4/-acetylsulfamethazine were identified in the liver. No strain-related differences were noted in sulfamethazine metabolism in a study with Fischer-344 male rats. 17 references, 4 figures, 6 tables.