Pharmacokinetics of Ceftiofur‐Related Residues in Rabbits After Single Intravenous and Intramuscular Administration

Ceftiofur is a third-generation cephalosporin widely used in veterinary medicine; however, pharmacokinetic data in rabbits remain limited. This study aimed to characterize the pharmacokinetics of ceftiofur in rabbits following single intravenous (IV) and intramuscular (IM) administration and to evaluate its potential antibacterial efficacy using pharmacokinetic/pharmacodynamic (PK/PD) indices. Ceftiofur was administered at a dose of 2 mg/kg body weight (BW) via IV and IM routes. Plasma ceftiofur-related concentrations (expressed as desfuroylceftiofur acetamide, DCA) were quantified using a validated analytical method, and pharmacokinetic parameters were determined by noncompartmental analysis. Following IM administration, ceftiofur was rapidly absorbed, with a median time to peak concentration (Tmax) of 2 h and a high absolute bioavailability (88.72%). The drug exhibited moderate distribution, with a volume of distribution (VZ) of 1.93 L/kg and a steady-state volume of distribution (VSS) of 0.85 L/kg, and was eliminated slowly, with a systemic clearance of 0.083 L/h/kg. The mean residence time (MRT; 9.95 h) after IM administration was not longer than that observed after IV administration (10.34 h), precluding reliable estimation of the absorption half-life. Based on PK/PD analysis assuming a minimum inhibitory concentration (MIC) of ≤ 1.0 μg/mL, the calculated time above MIC (T > MIC) values following single IV and IM administration were approximately 4 and 5 h, respectively. These results indicate that although ceftiofur is rapidly and extensively absorbed in rabbits, a single IV or IM dose of 2 mg/kg BW may be insufficient to achieve effective exposure against bacterial pathogens with MIC values ≥ 1.0 μg/mL.