Pharmacokinetics of phenobarbital after repeated oral administration in normal horses.

This research aims to understand the impact of continuously administering the drug phenobarbital, a type of anticonvulsant, to healthy horses.

Introduction

• Phenobarbital is a known effective anticonvulsant used in humans and canines. It has also been recommended for treating seizure disorders in horses, particularly in foals affected by idiopathic benign epilepsy and those suffering from seizures due to neonatal maladjustment syndrome.
• Decades of research have examined the kinetics of phenobarbital when administered orally and intravenously in humans, dogs, and mature horses. The studies highlight its inducing effect on microsomal enzymes, which can modify the drug’s metabolism with sustained administration.
• Despite having tested the pharmacokinetics of this drug after repeated oral administration in humans and dogs, no studies have been carried out for horses. This research aims to fill that gap.

Methodology

• The study involves three female and three castrated male adult horses of different ages and breeds, all weighing between 450-550 kg. These horses were not on any medication for 30 days before the experiment and were all found to be clinically healthy after history checks and physical examinations.
• The horses were administered an intravenous dose of Sodium phenobarbital. Blood samples were then collected at various intervals up until 72 hours.
• For the next ten days, phenobarbital tablets dissolved in water were given to these horses once daily. Further blood samples were collected 24 hours after the last administered oral dose.
• On the 17th day, a second intravenous dose of Sodium phenobarbital was given followed by blood collection intervals similar to the first dosage.
• The collected blood samples were allowed to clot, centrifuged to separate the serum which was then stored at -70°C. The serum concentrations of phenobarbital were determined in duplicate using radioimmunoassay – a lab technique used to measure concentrations of antigens.

Data Analysis

• For each horse, 1- and 2-compartment models were fitted to serum concentration versus time data using non-linear least squares analysis.
• The best model was determined using Akaike’s Information Criterion, a method used for model selection.
• The study then proceeds to interpret the processed data, but stops abruptly at the discussion of the calculation method for estimating the area under their concentration versus time curve.