Pharmacokinetics of ceftiofur crystalline-free acid sterile suspension in the equine.

This research investigates how horses metabolize (process) ceftiofur, an antibiotic often used in veterinary medicine. The study involves looking at the manner and speed with which the drug is absorbed, distributed, metabolized and excreted. Specifically, it tests the absolute bioavailability and dose proportionality of ceftiofur and establishes the drug’s effectiveness in horses.

Absolute Bioavailability Study

• The absolute bioavailability study refers to the extent that a drug is effectively absorbed into the system and is capable of having an active effect.
• In this study, thirty horses were either given an intravenous dose of 1.0 mg/kg of the antibiotic ceftiofur sodium or an intramuscular (I.M.) dose of ceftiofur crystalline-free acid (CCFA) at 6.6 mg/kg.
• The research found the absorption of CCFA to be excellent, demonstrating a bioavailability of 100%, which means the drug was completely absorbed into the horse’s system when administered intramuscularly.

Dose Proportionality Study

• A total of 48 horses received daily I.M. ceftiofur sodium injections at 1.0 mg/kg for ten doses or two doses of CCFA spaced out by 96 hours. The CCFA doses varied at 3.3, 6.6, or 13.2 mg/kg. The study aimed to understand whether the effect of the drug is proportional to the dosage given.
• The findings indicated that AUC(0-∞) and C(max) (measures of the overall drug exposure within the body and the maximum drug concentration, respectively) were increased in a dose-related manner.
• The least-squares mean terminal half-life (t(½) ) for the last out of ten daily i.m. doses of ceftiofur sodium at 2.2 mg/kg was found to be 40.8 h, whereas, it was 100 h for the second i.m. dose of CCFA at 6.6 mg/kg. This shows that CCFA stays in the body for a longer period, which can affect its efficacy.

Outcome and Predictions

• The study concluded that keeping plasma ceftiofur equivalent concentrations more than a threshold concentration of 0.2 μg/mL is linked with efficacy. In this case, it was observed that after two 6.6 mg/kg doses of CCFA, the mean time for the concentration to remain above 0.2 μg/mL was 262 hours.
• The researchers also used simulations with the nonlinear mixed-effect PK model, predicting that more than 97.5% of horses will maintain plasma ceftiofur equivalent concentrations greater than 0.2 μg/mL for 96 h after the second 6.6 mg/kg dose of CCFA.