Pharmacokinetics of phenytoin (diphenylhydantoin) in horses.

This study looks into the behavior of the anti-seizure drug, phenytoin, in horses after oral and intravenous administration. A model was used to make sense of this behavior and the drug’s bioavailability was found to be fairly low after oral administration, necessitating dose adjustments for oral use.

Study Overview

• The research aims to understand how Phenytoin, an anti-convulsant or anti-seizure drug, behaves or is processed in a horse’s body (its pharmacokinetics) after giving it either by mouth (orally) or in the vein (intravenously).
• The drug was given as a single dose to a group of healthy horses and the concentration of the drug in the blood was measured over a period to help establish dosage recommendations.

Research Method

• A single dose of phenytoin (8.8 mg/kg body weight) was given intravenously to nine horses and a higher dose (13.2 mg/kg) was given to one horse.
• The researchers used a two-compartment open model which allows the drug to go in and out of the compartments freely without any restrictions. This model helps to understand the behavior of the drug in the body.
• The experiment was later repeated with some of the horses (three that received 8.8 mg/kg and the one that received 13.2 mg/kg), but this time the dose was given orally and three days after the initial dose.

Results

• Phenytoin peaked in concentration in the horse’s bloodstream within 1-4 hours after oral administration.
• The research team found that the drug was poorly absorbed when given by mouth, with a bioavailability of only 34.5 ± 8.6%. Bioavailability measures the proportion of a drug that enters the body’s circulation and can have an active effect.
• Therefore, the amount of the drug that is actually available to exert an effect after oral administration is much lower than the amount that was initially administered.
• As such, they suggested dosing adjustments to achieve the desired average serum steady-state concentrations (when the amount of drug going into the body equals the amount being processed and excreted out of the body) of 5 and 10 micrograms/ml for phenytoin when given orally. This would involve giving the drug every 8 hours.