Plasma and urine disposition and dose proportionality of ceftiofur and metabolites in dogs after subcutaneous administration of ceftiofur sodium

Abstract

Nine male dogs (10.3-13.5 kg body weight) were randomly assigned to three groups of three dogs each and administered ceftiofur sodium subcutaneously as a single dose of 0.22, 2.2, or 4.4 mg ceftiofur free acid equivalents/kg body weight. Plasma and urine samples were collected serially for 72 h and assayed for ceftiofur and metabolites (derivatized to desfuroylceftiofur acetamide) using high-performance liquid chromatography. Urine concentrations remained above the MIC90 for Escherichia coli (4.0 micrograms/mL) and Proteus mirabilis (1.0 micrograms/mL) for over 24 h after doses of 2.2 mg/kg (8.1 micrograms/mL) and 4.4 mg/kg (29.6 micrograms/mL), the interval between treatments for ceftiofur sodium in dogs, whereas urine concentrations 24 h after dosing at 0.22 mg/kg (0.1 mg/Ib) were below the MIC90 for E. coli and P. mirabilis (0.6 microgram/mL). Plasma concentrations were dose-proportional, with peak concentrations of 1.66 +/- 0.0990 micrograms/mL, 8.91 +/- 6.42 micrograms/mL, and 26.7 +/- 1.07 micrograms/mL after doses of 0.22, 2.2, and 4.4 mg/kg, respectively. The area under the plasma concentration versus time curve, when normalized to dose, was similar across all dosage groups.