title: Pharmacokinetics of ceftiofur crystalline-free acid sterile suspension in the equine.
abstract: Absolute bioavailability and dose proportionality studies were performed with ceftiofur in horses. In the absolute bioavailability study, thirty animals received either an intravenous dose of ceftiofur sodium at 1.0 mg/kg or an intramuscular (i.m.) dose of ceftiofur crystalline-free acid (CCFA) at 6.6 mg/kg. In the dose proportionality study, 48 animals received daily i.m. ceftiofur sodium injections at 1.0 mg/kg for ten doses or two doses of CCFA separated by 96 h, with CCFA doses of 3.3, 6.6, or 13.2 mg/kg. Noncompartmental and mixed-effect modeling procedures were used to assess pharmacokinetics (PK). CCFA was well absorbed with a bioavailability of 100%. AUC(0-∞) and C(max) increased in a dose-related manner following administration of the two doses of CCFA at 3.3, 6.6, and 13.2 mg/kg. The least-squares mean terminal half-life (t(½) ) following the tenth daily i.m. injection of ceftiofur sodium at 2.2 mg/kg was 40.8 h, but the least-squares mean t(½) following the second i.m. injection of CCFA at 6.6 mg/kg was 100 h. The time that plasma ceftiofur equivalent concentrations remain above a threshold concentration of 0.2 μg/mL has been associated with efficacy, and following administration of two 6.6 mg/kg doses of CCFA, the mean time above 0.2 μg/mL was 262 h. Simulations with the nonlinear mixed-effect PK model predicted that more than 97.5% of horses will have plasma ceftiofur equivalent concentrations >0.2 μg/mL for 96 h after the second 6.6 mg/kg dose of CCFA.
authors.affiliation: Veterinary Medicine Research and Development, Pfizer Animal Health, Kalamazoo, MI 49007, USA. Wendy.Collard@pfizer.com
authors.forename: W T
authors.initials: WT
authors.lastname: Collard
authors.forename: S R
authors.initials: SR
authors.lastname: Cox
authors.forename: S P
authors.initials: SP
authors.lastname: Lesman
authors.forename: G S
authors.initials: GS
authors.lastname: Grover
authors.forename: J F
authors.initials: JF
authors.lastname: Boucher
authors.forename: J W
authors.initials: JW
authors.lastname: Hallberg
authors.forename: J A
authors.initials: JA
authors.lastname: Robinson
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004333:Drug Administration Routes; D005260:Female; D006207:Half-Life; D006736:Horses / Q000097:blood*; D008297:Male; D013535:Suspensions
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D013535:Suspensions; C053503:ceftiofur