Pharmacokinetics of intravenous ceftiofur sodium and concentration in body fluids of foals.

This research study primarily focused on examining the behavior of the antibiotic ceftiofur when administered intravenously in young foals. The researchers looked at how the drug is distributed and metabolized in the body (pharmacokinetics) and also assessed its efficacy against common pathogens affecting horses.

Research Design and Methodology

• The research was executed in a cross-over design, involving two groups of foals at different ages. One group consisted of very young foals (1-2 days old) and the other of slightly older foals (4-5 weeks old). The foals in each group were given either 5mg/kg or 10mg/kg doses of intravenous ceftiofur.
• In addition, a separate group of six foals between 1 and 5 days of age were given five doses of ceftiofur at a dosage of 5mg/kg every 12 hours to assess the behavior of the drug under repeated administration.
• To evaluate how the drug was processed in the body, concentrations of desfuroylceftiofur acetamide (DCA) – a metabolite of ceftiofur – were measured in various bodily fluids including blood plasma, synovial fluid, urine and cerebrospinal fluid (CSF) using ultra-high performance liquid chromatography tandem mass spectometry (UPLC-MS/MS).
• A subset of plasma samples were subjected to a microbiologic assay to measure the activity of ceftiofur, as a means of comparing this method of measurement with UPLC-MS/MS.
• The researchers also determined the minimum inhibitory concentration (MIC) of ceftiofur – the lowest concentration of ceftiofur necessary to prevent bacterial growth – for several common equine bacterial pathogens.

Key Findings

• Following the administration of a 5mg/kg dose to 1-2 day-old foals, DCA demonstrated a half-life of approximately 8 hours, indicating the body processes nearly half the received dose in this timeframe.
• The clearance and distribution figures from the study imply that ceftiofur is efficiently removed and well distributed within the equine body.
• After multiple doses of 5mg/kg, DCA concentrations in CSF were found to be significantly lower than in plasma, suggesting that ceftiofur does not readily penetrate the brain barrier in foals.
• The researchers discovered that the microbiologic assay significantly underestimated plasma concentrations of DCA when compared to UPLC-MS/MS measurements.
• Also, the study revealed that a relatively low MIC (<0.5 microg/mL) of ceftiofur is required to inhibit growth of 90% of isolates of certain bacteria commonly found in horses, such as Escherichia coli, Pasteurella spp, Klebsiella spp, and beta-hemolytic streptococci.
• Finally, the researchers concluded that intravenous administration of ceftiofur sodium at the rate of 5 mg/kg every 12 hours should provide adequate coverage for the treatment of infections caused by susceptible bacterial isolates in foals.