title: Pharmacokinetics of ceftiofur and metabolites after single intravenous and intramuscular administration and multiple intramuscular administrations of ceftiofur sodium to sheep.
abstract: Twenty-four sheep (38.0-54.1 kg body wt) were allocated into four treatment groups and dosed with ceftiofur sodium at 1.1 mg ceftiofur free acid equivalents (CFAE)/kg or 2.2 CFAE/kg using a complete two-route (intravenous, i.v.: intramuscular, i.m.), two-period crossover design, with a two-week washout between injections. After another two-week washout period, 12 sheep were selected and dosed with ceftiofur sodium i.m. for five consecutive days at either 1.1 or 2.2 mg CFAE/kg. After all injections, blood samples were obtained serially for determination of serum concentrations of ceftiofur and metabolites. The terminal phase half-lives derived from the last 3-5 concentration-time points were 350 and 292 min (harmonic means) after i.v. doses of 1.1 and 2.2 mg/kg, respectively, and 389 and 459 min after i.m. doses of 1.1 and 2.2 mg/kg, respectively. The i.m. bioavailability of ceftiofur sodium in sheep was 100%, and the area under the curve from time 0 to the limit of quantitation (AUC0 LOQ) was dose-proportional from 1.1-2.2 mg CFAE/kg body wt in sheep. After 5 daily i.m. doses of ceftiofur sodium at either 1.1 or 2.2 mg CFAE/kg there was minimal accumulation of drug in serum as assessed by the observed maximum serum concentration (Cmax), and serum concentrations were dose-proportional after the multiple dosing regimen.
authors.affiliation: Environmental Toxicology Extension, University of California, Davis 95616, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Craigmill
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
authors.forename: S E
authors.initials: SE
authors.lastname: Wetzlich
authors.forename: C R
authors.initials: CR
authors.lastname: Gustafson
authors.forename: T S
authors.initials: TS
authors.lastname: Arndt
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008954:Models, Biological; D012756:Sheep / Q000097:blood*
chemical_list: D002511:Cephalosporins; C053503:ceftiofur