IN-VITRO METABOLISM OF CEFTIOFUR IN BOVINE-TISSUES

The metabolism of ceftiofur in bovine kidney, liver, muscle and lung, and the effects of the presence of cystine and glutathione in the medi a were evaluated using S-9 and microsomal tissue fractions. Conversion of ceftiofur to desfuroylceftiofur (DFC) was catalyzed by an esterase which was most active in kidney, followed by liver. It was not very a ctive in muscle and lung. After DFC was liberated, it rapidly bound pr imarily to tissue proteins (> 56%), and was also conjugated to cystein e and glutathione. Production of DFC-cysteine by disulfide exchange of DFC with cystine and production of DFC-glutathione by conjugation of DFC to glutathione occurred in buffer if glutathione and cystine were present in the medium. These conjugations were also observed in incuba tions with tissue fractions, indicating that they were not inhibited b y the tissues endogenous molecules. In addition, the metabolism of DFC -glutathione to DFC-cysteine was observed when tissue proteins were pr esent. The metabolism of DFC-glutathione to DFC-cysteine was faster in kidney than in liver. Metabolites devoid of an intact beta-lactam rin g were not observed in these in vitro studies.