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 (AUC(O-LOQ)), and (2) time concentrations remained above 0.2 mug/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 mug/mL was observed from 0.67-2.0 h after i.m. administration, whereas a C-max of 13.6 +/- 3.85 mug/mL was observed from 0.67-3.0 h after s.c. administration. The AUC(O-LOQ) was 108 +/- 35.0 mug.h/mL after i.m. dosing, compared with 105 +/- 29.8 mug.h/mL after s.c. dosing. The pre-established criterion for equivalence of the AUC(O-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(O-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.