Pharmacokinetics of chloramphenicol base in horses and comparison to compounded formulations.

This research article explores the pharmacokinetics of the antibiotic chloramphenicol in horses, comparing the canine-approved tablets with compounded paste and suspension forms. The researchers hypothesized that chloramphenicol has low absorption and a short half-life in horses, leading to low serum concentrations. They also theorized that the compounded forms have lower relative bioavailability. The study found that all formulations did not reach the recommended bacteria-killing concentration and that further studies are needed, particularly for bacteria with lower sensitivity.

Research Methodology

• Seven horses participated in this study and were administered canine-approved chloramphenicol tablets at a dose of 50 mg/kg orally.
• In a crossover design, the horses were also administered two compounded preparations (paste and suspension) at the same dose, allowing for a direct comparison between all three formulations.
• The experiment measured and compared the peak concentration (C), time to peak concentration, elimination half-life, and area under the curve (AUC) for each formulation. These are common parameters used in pharmacokinetic studies to understand the absorption, distribution, metabolism, and excretion of a drug.

Results and Findings

• The peak concentrations of the drug in the horses’ bloodstream and the time to reach these concentrations varied slightly between the tablet, paste, and suspension forms. However, none of the formulations reached the minimum inhibitory concentration (MIC) of 8 μg/ml, which is recommended by the Clinical Laboratory Standards Institute (CLSI) for most bacteria.
• The elimination half-life, which is the time for the drug concentration in the body to decrease by half, was also found to be slightly different for each form.
• The area under the curve (AUC), which generally represents the total drug exposure over time, was highest for the tablets, followed by the paste and the suspension, indicating that the total absorption of the drug was highest from the tablet form.
• The relative bioavailability, or the extent of drug absorption, of the compounded suspension and paste was found to be 78.1% and 90.6% respectively when compared with the tablets.

Implications and Recommendations

• As none of the formulations reached the recommended MIC for most bacteria, the study suggests that chloramphenicol may not be optimally effective for treating bacterial infections in horses, especially those caused by bacteria with higher MIC values.
• Due to the low serum concentrations found, the researchers recommend targeting bacteria with MIC values lower than those recommended by CLSI in adult horses.
• The study concludes that further multidose studies are necessary to better understand and optimize the use of chloramphenicol in horses.