title: Comparison of plasma pharmacokinetics and bioavailability of ceftiofur sodium and ceftiofur hydrochloride in pigs after a single intramuscular injection.
abstract: Ceftiofur sodium, a broad-spectrum cephalosporin, is active against gram-positive and gram-negative pathogens of veterinary importance. Two studies were designed to compare the intramuscular bioavailability of the current sodium salt and the new hydrochloride salt in pigs at doses of either 3 mg or 5 mg ceftiofur equivalents (CE)/kg body weight. Twenty-six healthy young pigs were selected for these two-period, two-treatment crossover studies, 12 for the 3 mg/kg study and 14 for the 5 mg/kg study. Each animal received one intramuscular (i.m.) injection of ceftiofur sodium and one i.m. injection of ceftiofur hydrochloride with a 14-day washout period between the two treatments. Blood samples were collected serially for up to 96 h postinjection. Plasma samples were then analysed using a validated assay that measures ceftiofur and all desfuroylceftiofur-related metabolites by high-performance liquid chromatography. In the 3 mg/kg dosage study, average maximum plasma concentration (C(max)) after administration of ceftiofur sodium was 15.8+/-3.40 microg/mL at 0.4-4 h after injection. After administration of ceftiofur hydrochloride, the C(max) was 11.8+/-1.67 microg/mL at 1-4 h after injection. Concentrations of ceftiofur and metabolites 72 h after the injection were 0.392+/-0.162 microg/mL for ceftiofur hydrochloride and 0.270+/-0.118 microg/mL for ceftiofur sodium. The mean area under the curve (AUC), from time 0 to the limit of quantitation (AUC(O-LOQ)) after ceftiofur hydrochloride administration, was 216+/-28.0 microg x h/mL, compared to 169+/-45.4 microg x h/mL after ceftiofur sodium administration. The calculated time during which plasma concentrations remained above 0.02 microg/mL (t(>0.2)) was 85.3+/-10.6 h for ceftiofur sodium and 77.2+/-10.7 h for ceftiofur hydrochloride. In the 5 mg/kg dosage study, C(max) after administration of ceftiofur sodium was 28.3+/-4.45 microg/mL at 0.33-2 h after injection. After administration of ceftiofur hydrochloride, the C(max) was 29.7+/-6.72 microg/mL at 0.66-2 h after injection. Concentrations of ceftiofur and metabolites 96 h after the injection were 0.274+/-0.0550 microg/mL for ceftiofur hydrochloride and 0.224+/-0.0350 microg/mL for ceftiofur sodium. The mean AUC(O-LOQ) after ceftiofur hydrochloride administration was 382+/-89.8 microg x h/mL compared to 302+/-54.4 microg x h/mL after ceftiofur sodium administration. The t(>0.2) was 78.9+/-9.65 h for ceftiofur sodium and 94.2+/-8.64 h for ceftiofur hydrochloride. Based on the similarity of the pharmacokinetic parameters of the sodium and hydrochloride formulations of ceftiofur, similar therapeutic efficacy can be inferred for the two products.
authors.affiliation: Animal Health Product Development, Pharmacia & Upjohn Company, Kalamazoo, MI 49001, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
authors.forename: B J
authors.initials: BJ
authors.lastname: Hanson
authors.forename: A
authors.initials: A
authors.lastname: Mignot
authors.forename: L
authors.initials: L
authors.lastname: Millérioux
authors.forename: P J
authors.initials: PJ
authors.lastname: Hamlow
authors.forename: V L
authors.initials: VL
authors.lastname: Hubbard
authors.forename: J K
authors.initials: JK
authors.lastname: Callahan
authors.forename: F M
authors.initials: FM
authors.lastname: Kausche
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular / Q000662:veterinary; D008297:Male; D013552:Swine / Q000378:metabolism*
chemical_list: D002511:Cephalosporins; C053503:ceftiofur