Pharmacokinetics of phenobarbital in horses after single and repeated oral administration of the drug.

The study examines how phenobarbital, a medicine usually used to treat seizures, is processed in the bodies of horses. It was found that the time it took for the drug to be eliminated from the body and how fast it was cleared from the body, changed significantly when the horses were given repeated doses of the drug over 42 days.

Study Design and Procedures

• The research involved six healthy fully grown horses who received a single dose of phenobarbital at 26 mg/kg of body weight, followed by multiple 13 mg/kg doses for 42 consecutive days.
• Seventeen venous blood samples were taken from each horse after the single dose, and then again after the final dose on day 42. The samples were analyzed to determine the plasma concentration of phenobarbital in the horses’ bloodstream.
• The researchers used a fluorescence assay, a tool that can measure the presence of specific substances in a sample, validated for use in horses to determine the concentration of phenobarbital.
• Additional blood samples were taken on days 8 and 25 to establish peak and trough concentrations as well as the overall body clearance of the drug.

Results and Interpretation

• After analysis, it was found that the average values for time taken for elimination of the drug from the body, volume of distribution in the body and clearance from the body varied after a single dose versus repeated doses over 42 days.
• The half-life of the drug (time taken for the drug quantity to reduce to half) decreased from around 24.2 hours after a single dose to around 11.2 hours after repeated doses.
• Additionally, the oral clearance rate (how fast the body eliminates the drug) increased significantly with repeated dosing.
• These changes suggest an induced enzyme response, where the body adapts to the repeated presence of the drug and processes it faster over time. This is highlighted by the significant increase of the enzyme gamma-glutamyltransferase activity in three out of the six horses after 42 days of dosing.
• The researchers concluded that because oral clearance increased over the 42 days, dosage adjustments may be needed when giving phenobarbital to horses over longer periods of time.