title: Pharmacokinetics of intravenous ceftiofur sodium and concentration in body fluids of foals.
abstract: The objectives of this study were to determine pharmacokinetics of intravenous (i.v.) ceftiofur in foals, to compare ultra-high performance liquid chromatography tandem mass spectometry (UPLC-MS/MS) and microbiologic assay for the measurement of ceftiofur concentrations, and to determine the minimum inhibitory concentration (MIC) of ceftiofur against common equine bacterial pathogens. In a cross-over design, ceftiofur sodium was administered i.v. to six foals (1-2 days-of-age and 4-5 weeks-of-age) at dosages of 5 and 10 mg/kg. Subsequently, five doses of ceftiofur were administered i.v. to six additional foals between 1 and 5 days of age at a dose of 5 mg/kg q 12 h. Concentrations of desfuroylceftiofur acetamide (DCA), the acetamide derivative of ceftiofur and desfuroylceftiofur-related metabolites were measured in plasma, synovial fluid, urine, and CSF by use of UPLC-MS/MS. A microbiologic assay was used to measure ceftiofur activity for a subset of plasma samples. Following i.v. administration of ceftiofur at a dose of 5 mg/kg to 1-2 day-old foals, DCA had a t(1/2) of 7.8 +/- 0.1 h, a body clearance of 74.4 +/- 8.4 mL/h/kg, and an apparent volume of distribution of 0.83 +/- 0.09 L/kg. After multiple i.v. doses at 5 mg/kg, DCA concentrations in CSF were significantly lower than concurrent plasma concentrations. Ceftiofur activity using a microbiologic assay significantly underestimated plasma concentrations of DCA. The MIC of ceftiofur required to inhibit growth of 90% of isolates of Escherichia coli, Pasteurella spp, Klebsiella spp, and beta-hemolytic streptococci was <0.5 microg/mL. Intravenous administration of ceftiofur sodium at the rate of 5 mg/kg every 12 h would provide sufficient coverage for the treatment of susceptible bacterial isolates.
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: S
authors.initials: S
authors.lastname: Meyer
authors.forename: S
authors.initials: S
authors.lastname: Giguère
authors.forename: R
authors.initials: R
authors.lastname: Rodriguez
authors.forename: R J
authors.initials: RJ
authors.lastname: Zielinski
authors.forename: G S
authors.initials: GS
authors.lastname: Grover
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006095:Gram-Positive Cocci / Q000187:drug effects*; D006736:Horses / Q000378:metabolism* / Q000382:microbiology; D007262:Infusions, Intravenous / Q000662:veterinary; D007709:Klebsiella / Q000187:drug effects; D016014:Linear Models; D008297:Male; D010325:Pasteurella / Q000187:drug effects; D015610:Serum Bactericidal Test / Q000662:veterinary; D013292:Streptococcus agalactiae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C053503:ceftiofur