Endogenous concentrations, pharmacokinetics, and selected pharmacodynamic effects of a single dose of exogenous GABA in horses.

This study investigates the natural levels of the neurotransmitter GABA in horses, as well as how a single dose of additional GABA is processed in the body and what effects it has. A total of 147 horses were studied, and high variability in GABA levels was observed. By tracking GABA concentrations in blood, urine, and cerebrospinal fluid, the researchers were able to determine how a single dose of GABA is absorbed, metabolized, and excreted in horses. The study found limited bioavailability with oral administration, transient sedative effects after intravenous administration, and reduced gastrointestinal activity after both methods of administration.

Study Methods and Findings

• The research sought to measure the natural concentrations of GABA in horses. Blood was taken from 147 horses and the mean GABA level was calculated to be 36.4 ng/mL.
• In order to study the absorption, metabolism and excretion of GABA – pharmacokinetics – 16 horses were administered a single dose of GABA, either intravenously or orally. The given dose was 1650 mg.
• Samples of blood, urine, and cerebrospinal fluid were collected over the following 48 hours. The researchers used liquid chromatography-mass spectrometry (LC-MS) to detect and quantify the GABA in these samples.
• Pharmacokinetic analysis revealed that plasma clearance and the volume of distribution for the central and peripheral compartments were 155.6 and 147.6 L/h, and 0.154 and 7.39 L respectively. Terminal elimination half-lives were 22.1 minutes for intravenous administration and 25.1 minutes for oral administration. The oral bioavailability was found to be 9.81%.

Pharmacodynamic Effects

• The effects of GABA were observed by monitoring heart rate, gastrointestinal activity, and general behavior. These are known as pharmacodynamic effects.
• Horses exhibited transient sedative-like effects following intravenous administration of GABA. These effects were not observed after oral administration.
• Heart rate was noted to increase for one hour following intravenous administration, while gastrointestinal sounds decreased for approximately 30 minutes after both oral and intravenous administration.
• The concentration of GABA in the cerebrospinal fluid did not show any significant increase, indicating that exogenously administered GABA does not appear to enter the central nervous system to a large extent.