Comparison of plasma pharmacokinetics and bioequivalence of ceftiofur sodium in cattle after a single intramuscular or subcutaneous injection

Ceftiofur sodium, a broad‐spectrum cephalosporin, is active against gram‐positive and gram‐negative pathogens of veterinary importance. This study was designed to compare the bioequivalence of the sodium salt in cattle after a single intramuscular (i.m.) or subcutaneous dose (s.c.) of 2.2 mg ceftiofur equivalents/kg body weight. The criteria used to evaluate bioequivalence were (1) the area under the curve from time of injection to the limit of quantitation (LOQ) of the assay (AUC0‐LOQ), and (2) time concentrations remained above 0.2 μg/mL (t>0.2). Twelve crossbred beef cattle were enrolled in a three‐period, two‐treatment crossover trial, with a minimum 2‐week washout period between doses of 2.2 mg ceftiofur equivalents/kg. Blood samples were collected serially for up to 72 h post‐injection. Plasma samples were then analyzed using a validated assay that measures ceftiofur, and all desfuroylceftiofur‐related metabolites, by high‐performance liquid chromatography (HPLC) as the stable derivative, desfuroylceftiofur acetamide. A maximum plasma concentration (Cmax) of 13.9±3.55 μg/mL was observed from 0.67−2.0 h after i.m. administration, whereas aCmax of 13.6±3.85 μg/mL was observed from 0.67–3.0 h after s.c. administration. TheAUC0‐LOQ was 108±35.0 μg · h/mL after i.m. dosing, compared with 105±29.8 μg · h/mL after s.c. dosing. The pre‐established criterion for equivalence of theAUC0‐LOQ for the i.m. and s.c. routes of administration was satisfied. Thet>0.2 was 49.2±8.55 h after i.m. administration, compared with 47.0±9.40 h after s.c. administration. The pre‐established criterion for equivalence of thet>0.2 for i.m. and s.c. administration was satisfied. The equivalence ofAUC0‐LOQ andt>0.2 for i.m. and s.c. administration of 2.2 mg ceftiofur equivalents (CE)/kg doses of ceftiofur sodium suggest similar therapeutic efficacy and systemic safety for the two routes of administration.