CONCENTRATION OF CEFTIOFUR METABOLITES IN THE PLASMA AND LUNGS OF HORSES FOLLOWING INTRAMUSCULAR TREATMENT

Ceftiofur sodium, a broad spectrum cephalosporin antibiotic approved f or veterinary use, is metabolized to desfuroylceftiofur which is conju gated to micro as well as macromolecules. Twelve horses, weighing 442- 618 kg, were injected intramuscularly with a single dose of 2.2 mg cef tiofur/kg (1.0 mg/lb) body weight. Blood was collected at various inte rvals over 24 h after treatment. Three groups of four horses each were euthanized and lungs were collected at 1, 12, and 24 h after treatmen t. The concentration of desfuroylceftiofur and desfuroylceftiofur conj ugates in the plasma and lungs was determined by converting them to de sfuroylceftiofur acetamide (DCA) and measured DCA by high performance liquid chromatography with UV detection. The average maximum concentra tion (C(max)) of desfuroylceftiofur and related metabolites in plasma expressed as ceftiofur equivalents was 4.46 +/- 0.9 3 mug/ml occurred at 1.25 +/- 0.46 h after treatment. These concentrations declined to 0 .99 +/- 0.16, 0.47 +/- 0.1 5 and 0.17 +/- 0.02 mug/ml at 8, 12, and 24 h, respectively. The mean residence time of ceftiofur metabolites was 6.10 +/- 1.27 h. Concentration of desfuroylceftiofur and desfuroylcef tiofur conjugates in the lungs of horses expressed as ceftiofur equiva lents were 1.40 +/- 0.36, 0.27 +/-0.07, and 0.15 +/- 0.08 mug/ml at 1, 12, and 24 h, respectively. These concentrations of the drug at 12 an d 24 h in lung homogenate were similar but slightly lower than plasma concentrations in the same horses, and the plasma pharmacokinetic valu es including half-life were similar to those observed at the approved dose of 1.1-2.2 mg ceftiofur/kg body weight administered intramuscular ly once daily for 3-5 days in cattle.