DISPOSITION OF CEFTIOFUR SODIUM IN SWINE FOLLOWING INTRAMUSCULAR TREATMENT

Ceftiofur displays a broad spectrum of bactericidal activity against b oth Gram-positive and Gramnegative bacteria including beta-lactamase-p roducing strains. Three to five milligrams of ceftiofur per kilogram o f body weight injected intramuscularly (im) on three consecutive days at 24-h intervals is recommended for bacteria-associated respiratory d isease in swine. Metabolism studies in 12 swine given 5 mg of [C-14]ce ftiofur/kg of body weight im for 3 consecutive days showed that 61.8 /- 4.7% of the dose was excreted in urine and 10.8 +/- 5.1%; of the do se was excreted in feces. The highest blood residues of about 15 ppm o f [C-14]ceftiofur free acid equivalent were observed at 2 h after trea tments, which declined to similar to 2 ppm at 24 h. Almost all of the radioactivity in the blood was found in the plasma, suggesting that th e drug did not penetrate the erythrocytes. Most of the radioactivity w as bound to macromolecules in the plasma and tissues. Desfuroylceftiof ur glutathione disulfide was found only in the liver and 3,3'-desfuroy lceftiofur disulfide (dimer) only in the urine. Desfuroylceftiofur cys teine disulfide was present in plasma, tissues, and urine. The structu res of the metabolites were deduced from HPLC comparison with syntheti c standards, proton NMR, and thermospray mass spectrometry. Polar meta bolites are present in urine and tissues after 12 h of treatment, indi cating beta-lactam and cepham ring opening. Details of disposition of ceftiofur in swine are presented and compared with rats from multiple oral dosing.