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

Abstract

The anti-anxiety and calming effects following activation of the GABA receptor have been exploited in performance horses by administering products containing GABA. The primary goal of the study reported here was to describe endogenous concentrations of GABA in horses and the pharmacokinetics, selected pharmacodynamic effects, and CSF concentrations following administration of a GABA-containing product. The mean (±SD) endogenous GABA level was 36.4±12.5ng/mL (n=147). Sixteen of these horses received a single intravenous and oral dose of GABA (1650mg). Blood, urine, and cerebrospinal fluid (n=2) samples were collected at time 0 and at various times for up to 48h and analyzed using LC-MS. Plasma clearance and volume of distribution was 155.6 and 147.6L/h and 0.154 and 7.39L for the central and peripheral compartments, respectively. Terminal elimination half-life was 22.1 (intravenous) and 25.1 (oral) min. Oral bioavailability was 9.81%. Urine GABA concentrations peaked rapidly returning to baseline levels by 3h. Horses appeared behaviorally unaffected following oral administration, while sedative-like changes following intravenous administration were transient. Heart rate was increased for 1h postintravenous administration, and gastrointestinal sounds decreased for approximately 30min following both intravenous and oral administration. Based on a limited number of horses and time points, exogenously administered GABA does not appear to enter the CSF to an appreciable extent.