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

• Published in: Journal of veterinary pharmacology and therapeutics Vol. 23; no. 5; pp. 273 - 280
• Main Authors: Brown, S A, Chester, S T, Speedy, A K, Hubbard, V L, Callahan, J K, Hamlow, P J, Hibbard, B, Robb, E J
• Format: Journal Article
• Language: English
• Published: England 01.10.2000
• Subjects: Animals; Area Under Curve; Cattle - metabolism; Cephalosporins - administration & dosage; Cephalosporins - blood; Cephalosporins - pharmacokinetics; Female; Injections, Intramuscular - veterinary; Injections, Subcutaneous - veterinary; Male; Therapeutic Equivalency
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1046/j.1365-2885.2000.00271.x

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 microg/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 microg/mL was observed from 0. 67-2.0 h after i.m. administration, whereas a Cmax of 13.6+/-3.85 microg/mL was observed from 0.67-3.0 h after s.c. administration. The AUC0-LOQ was 108+/-35.0 microg. h/mL after i.m. dosing, compared with 105+/-29.8 microg. h/mL after s.c. dosing. The pre-established criterion for equivalence of the AUC0-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 AUC0-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.