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

Abstract

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 ( AUC 0‐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 ( C max) of 13.9±3.55 μg/mL was observed from 0.67−2.0 h after i.m. administration, whereas a C max of 13.6±3.85 μg/mL was observed from 0.67–3.0 h after s.c. administration. The AUC 0‐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 the AUC 0‐LOQ for the i.m. and s.c. routes of administration was satisfied. The t >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 the t >0.2 for i.m. and s.c. administration was satisfied. The equivalence of AUC 0‐LOQ and t >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.