Disposition of Ceftiofur Sodium in Swine following Intramuscular Treatment

Ceftiofur displays a broad spectrum of bactericidal activity against both Gram-positive and Gram-negative bacteria including beta-lactamase-producing strains. Three to five milligrams of ceftiofur per kilogram of body weight injected intramuscularly (im) on three consecutive days at 24-h intervals is recommended for bacteria-associated respiratory disease in swine. Metabolism studies in 12 swine given 5 mg of [14C]ceftiofur/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 dose was excreted in feces. The highest blood residues of about 15 ppm of [14C]ceftiofur free acid equivalent were observed at 2 h after treatments, which declined to approximately 2 ppm at 24 h. Almost all of the radioactivity in the blood was found in the plasma, suggesting that the drug did not penetrate the erythrocytes. Most of the radioactivity was bound to macromolecules in the plasma and tissues. Desfuroylceftiofur glutathione disulfide was found only in the liver and 3,3'-desfuroylceftiofur disulfide (dimer) only in the urine. Desfuroylceftiofur cysteine disulfide was present in plasma, tissues, and urine. The structures of the metabolites were deduced from HPLC comparison with synthetic standards, proton NMR, and thermospray mass spectrometry. Polar metabolites are present in urine and tissues after 12 h of treatment, indicating beta-lactam and cepham ring opening. Details of disposition of ceftiofur in swine are presented and compared with rats from multiple oral dosing