METABOLISM AND DISPOSITION BY THE RAT OF SULFADIAZINE-S-35 ALONE AND IN THE PRESENCE OF TRIMETHOPRIM

  • 1 January 1979
    • journal article
    • research article
    • Vol. 7  (2) , 94-99
Abstract
The tissue distribution and metabolism of 35S-sulfadiazine (I, SDZ) alone and in the presence of trimethoprim (TMP) was studied in the male rat. In the 72 h period following a single oral dose (30 mg/kg) of 35S-SDZ/TMP (5/1, wt/wt), 87% of the radioactivity was recovered in the urine and 15% of the radioactivity was recovered in the feces. The concentrations of drug-related material in the plasma or tissues after 72 h were < 0.1 ppm with the exception of the liver (0.13 ppm). Aside from intact drug, the 2 major urinary metabolites (> 5% of the radioactivity in urine) were N4-acetylsulfadiazine (II) and sulfadiazine N4-glucuronide (VI). Three minor urinary metabolites (< 5%) were identified as N4-acetyl-2-sulfanilamido-4-hydroxy-pyrimidine (IV), 2-sulfanilamido-4-hydroxypyrimidine (III) and 2-sulfanilamido-5-hydroxypyrimidine (V). Metabolites IV and V are novel metabolites of SDZ and have not been reported previously for any species. The relative amounts of sulfadiazine and its metabolites excreted in the urine and feces and the distribution of intact drug and 35S in rat tissues were determined. The metabolites were screened for antibacterial activity; the N4-acetylated metabolites II and IV were inactive, whereas the hydroxypyrimidine metabolites III and V were active against a few organisms, but in general much less active than I.

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