Pharmacokinetic parameters for single- and multi-dose regimens for subcutaneous administration of a high-dose ceftiofur crystalline-free acid to neonatal foals.

The research focuses on understanding the behavior of a high-dose antibiotic, specifically ceftiofur crystalline-free acid (CCFA), when administered subcutaneously (under the skin) in single and multiple dosing to very young (neonatal) foals. The findings suggest that this method of administration is safe and results in adequate plasma concentrations for treating several bacterial infections associated with septicemia in these young animals.

Study Design and Methodology

• The researchers set out to study the pharmacokinetics (how a drug is absorbed, distributed, metabolized and excreted) of CCFA when administered to 12 neonatal foals aged between 1 and 3 days. This was done with single-end multi-dose regimens.
• Six of the foals received a single subcutaneous dose, while the other six were given multiple doses (four in total) of CCFA every 48 hours.
• Blood samples were periodically taken after the drug administration to measure plasma concentrations of ceftiofur free acid equivalents (CFAE), a measure of the active form of the drug in the blood, using high-performance liquid chromatography.

Key Findings

• For the protocol involving a single dose of CCFA, the average maximum observed plasma concentration came out to be 3.1 ± 0.6 μg/mL, with the maximum concentration being generally observed about 14.0 ± 4.9 hours after administration.
• With the multiple dose protocol, the average durations when the plasma concentration of CFAE was above 0.5 μg/mL and 2.0 μg/mL were respectively 192.95 ± 15.86 hours and 78.80 ± 15.31 hours.
• The same multiple dose protocol showed the average area under the concentration versus time curve (AUC) – an important measure of the body’s exposure to the drug – was 246.2 ± 30.7 h × μg/mL after a single dose and 172.7 ± 27.14 h × μg/mL after multiple doses. This means concentration of the drug remained significantly high for a sufficient period of time after dosage.
• The study concluded that administering CCFA subcutaneously in foals at a dose of 13.2 mg/kg was well-tolerated and resulted in adequate plasma concentrations for treating a range of bacteria associated with septicemia (a serious bloodstream infection) in young foals.
• The results also suggested that giving multiple doses at 48-hour intervals proved effective in maintaining therapeutic concentrations of the drug in these young horses.