Pharmacokinetics of single-dose intragastric and intravenous pregabalin administration in clinically normal horses.

The research study evaluates the pharmacokinetics, or how the drug is absorbed, distributed, metabolized, and excreted, of a single dose of pregabalin administered either by intragastric or intravenous methods in healthy horses.

Methodology

• This study was conducted on five healthy adult mares. The horses were given a single dose of pregabalin (approximately 4 mg/kg) through a nasogastric tube.
• After a three-week period to let the drug completely wash out of their systems, the same dose was administered intravenously (IV).
• The researchers did not withhold food during this process.
• To measure pregabalin concentrations in plasma at various points of time (from 0 to 36 hours after the drug was administered), a method known as ultra-performance liquid chromatography with triple quadrupole tandem mass spectrometry was employed.
• The analysis of the pharmacokinetic variables was noncompartmental.

Results

• Some mild sedation was observed in two horses after both the intragastric and IV administrations of pregabalin. Following the IV administration, all the horses displayed mild, temporary signs of colic or abnormal behavior.
• After intragastric administration, the median maximal plasma concentration was 5.0 μg/mL, time to maximum plasma concentration was 1.0 hour, elimination half-life was approximately 8.0 hours, and the area under the curve from time zero until the end (AUC0-∞) was 47.2 μg·h/mL.
• After IV administration, the initial concentration was 22.2 μg/mL, the elimination half-life was approximately 7.74 hours, and the AUC0-∞ was 48.3 μg·h/mL.
• The bioavailability (the ability of the drug to enter the horse’s system) was 97.7%.
• The median predicted values for minimal, mean, and maximal steady-state plasma concentrations after intragastric administration with an 8-hour dosing interval were 3.9, 5.3, and 6.3 μg/mL, respectively.

Conclusion

• The study found that at a simulated intragastric dosage of about 4 mg/kg every 8 hours, the middle value of the steady-state plasma concentration of pregabalin in healthy horses was within the therapeutic range reported for humans.
• However, the study makes clear that the research does not extend to the therapeutic concentrations or the safety of this dosage in horses, indicating the need for further research in these areas.