Metabolism of ceftiofur. Nature of urinary and plasma metabolites in rats and cattle

Abstract

The metabolism of [14C]ceftiofur following intramuscular (im) administration to cattle and oral dosing in rats produced a single metabolite, desfuroylceftiofur, which was observed in the plasma of both species. Desfuroylceftiofur existed free in the plasma of cattle but was covalently bound to plasma proteins in rats. Urinary metabolites from both species appear qualitatively similar but quantitatively different depending on the dose, route of administration, and the time interval posttreatment. Most of the urinary metabolites in rats and cattle are derivatives of desfuroylceftiofur and are probably artifacts due to the ease of its oxidation in base, lactonization in acids, and hydrolysis of lactones. An interesting metabolite ceftiofur sulfoxide cysteine is the major metabolite in the urine of rats dosed orally at or above 100 mg/kg. However, it was not present at oral doses of 7-15 mg/kg nor after im treatment of cattle and rats.Ceftiofur (I-B, Table I) is very effective in control of Gram-positive and Gram-negative bacterial pathogens of veterinary importance both in vivo and in vitro (Yancey et al, 1986). Its sodium salt, NAXCEL, has recently been

High resolution mass spectrometry in the identification of transformation products and metabolites from β-lactam antibiotics in thermally treated milk

“…Among them, only TIO-2 (m/z 414.0533), identified as deacetylcefotaxime, has been previously described. This compound was found in studies about alkaline hydrolysis and metabolism of ceftiofur in rats [25,26]. TIO-1 fits with the structure resulting from ␤-lactam ring cleavage.…”

On-line coupling of solid-phase extraction and capillary electrophoresis for the determination of cefoperazone and ceftiofur in plasma

“…The detection limits were in the range of 50-100 ng ml −1 for the cephalosporins. Ceftiofur has been analyzed in plasma samples by HPLC-UV [4,[7][8][9]31] with detection limits in the 150 ng ml −1 range. So, the SPE-CE results presented here are comparable to those reported LC-UV methods.…”

Determination of ceftiofur in bovine plasma by HPLC-DAD

“…1) is a third generation broadspectrum cephalosporin, formulated as an intramuscular injection (Excenel ® ; Pharmacia, Sydney, NSW, Australia) which is used to treat respiratory diseases in swine, ruminants and horses [1]. The thioester bond on ceftiofur is rapidly cleaved to give desfuroylceftiofur which is further metabolized to a disulfide dimer and various desfuroylceftiofur-protein and amino acid conjugates [2,3]. Free desfuroylceftiofur is an active metabolite with the intact cephalosporin part of the molecule responsible for biological activity.…”