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  • Title: Pharmacokinetics of intravenous ceftiofur sodium and concentration in body fluids of foals.
    Author: Meyer S, Giguère S, Rodriguez R, Zielinski RJ, Grover GS, Brown SA.
    Journal: J Vet Pharmacol Ther; 2009 Aug; 32(4):309-16. PubMed ID: 19614835.
    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.
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