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

A liquid chromatographic (LC) method has been developed for the determination of the desfuroylceftiofur metabolite of ceftiofur as a residue in the plasma of animals. Plasma sample in 0.1 M pH 8.7 phosphate buffer containing dithioerythritol is Incubated under nitrogen for 15 min at 50°C. The sample is centrifuged, charged to a C18 cartridge, and washed with 0.1M ammonium acetate. The desfuroylceftiofur residue on the cartridge Is derivatized by adding 0.1M ammonium acetate containing iodoacetamide and letting the cartridge stand in the dark for 30 min. The cartridge is then drained and rinsed, and the desfuroylceftiofur acetamide is eluted with methanol. The mixture is evaporated to dryness, dissolved in pH 10.6 sodium hydroxide, and charged to a SAX cartridge. The derivative is eluted with 2% acetic acid, reduced In volume, and dissolved in mobile phase for liquid chromatography. The LC system includes a C8 column and guard cartridge with UV detection at 254 nm. The gradient mobile phase (flow rate 1 mL/mln) is 0.01M pH 5 ammonium acetate programmed to 29 % methanol-water (60 + 40) in 25 min. Recoveries were 90-100% with a sensitivity of 0.1 ppm or less. The procedure has been applied to the plasma of cattle, rats, horses, pigs, and dogs.

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Ceftiofur sodium, a broad spectrum cephalosporin antibiotic approved for veterinary use, is metabolized to desfuroylceftiofur which is conjugated to micro as well as macromolecules. Twelve horses, weighting 442-618 kg, were injected intramuscularly with a single dose of 2.2 mg ceftiofur/kg (1.0 mg/lb) body weight. Blood was collected at various intervals over 24 h after treatment. Three groups of four horses each were euthanized and lungs were collected at 1, 12, and 24 h after treatment. The concentration of desfuroylceftiofur and desfuroylceftiofur conjugates in the plasma and lungs was determined by converting them to desfuroylceftiofur acetamide (DCA) and measured DCA by high performance liquid chromatography with UV detection. The average maximum concentration (Cmax) of desfuroylceftiofur and related metabolites in plasma expressed as ceftiofur equivalents was 4.46 +/- 0.93 micrograms/ml occurred at 1.25 +/- 0.46 h after treatment. These concentrations declined to 0.99 +/- 0.16, 0.47 +/- 0.15 and 0.17 +/- 0.02 microgram/ml at 8, 12, and 24 h, respectively. The mean residence time of ceftiofur metabolites was 6.10 +/- 1.27 h. Concentrations of desfuroylceftiofur and desfuroylceftiofur conjugates in the lungs of horses expressed as ceftiofur equivalents were 1.40 +/- 0.36, 0.27 +/- 0.07, and 0.15 +/- 0.08 micrograms/ml at 1, 12, and 24 h, respectively. These concentrations of the drug at 12 and 24 h in lung homogenate were similar but slightly lower than plasma concentrations in the same horses, and the plasma pharmacokinetic values including half-life were similar to those observed at the approved dose of 1.1-2.2 mg ceftiofur/kg body weight administered intramuscularly once daily for 3-5 days in cattle.

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