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Pharmacokinetics of intravenous ceftiofur sodium and concentration in body fluids of foals
Author(s) -
MEYER S.,
GIGUÈRE S.,
RODRIGUEZ R.,
ZIELINSKI R. J.,
GROVER G. S.,
BROWN S. A.
Publication year - 2009
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2008.01041.x
Subject(s) - ceftiofur , pharmacokinetics , chemistry , horse , urine , acetamide , chromatography , medicine , pharmacology , zoology , cephalosporin , antibiotics , biochemistry , biology , paleontology , organic chemistry
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 ½ 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 β‐hemolytic streptococci was <0.5 μg/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.