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 ± 12.5 ng/mL (n = 147). Sixteen of these horses received a single intravenous and oral dose of GABA (1650 mg). Blood, urine, and cerebrospinal fluid (n = 2) samples were collected at time 0 and at various times for up to 48 h and analyzed using LC-MS. Plasma clearance and volume of distribution was 155.6 and 147.6 L/h and 0.154 and 7.39 L 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 3 h. Horses appeared behaviorally unaffected following oral administration, while sedative-like changes following intravenous administration were transient. Heart rate was increased for 1 h postintravenous administration, and gastrointestinal sounds decreased for approximately 30 min 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.

Quantitation of γ‐aminobutyric acid in equine plasma by hydrophilic interaction liquid chromatography with tandem mass spectrometry

“…The information regarding the calibrators and positive control samples was not provided in the other report . Methionine‐d 3 was used as the IS . We believe that the method described in our manuscript is more straightforward, fine‐tuned, and has higher throughput compared to the previously reported methods.…”

“…Previously at least two HPLC–MS/MS methods for the determination of GABA in equine plasma were reported for doping control purposes . In both cases, before analysis, samples were extracted and derivatized with EZ:faast‐Free (Physiological) Amino Acid Analysis kit from Phenomenex®.…”

“…The run times per sample were 13 and 20 min respectively. In one report calibrators and QC samples were prepared in water . The information regarding the calibrators and positive control samples was not provided in the other report .…”

“…There has been anecdotal evidence that GABA is used in competitive equine sports . GABA is present in the supplement known as “Carolina Gold” and rumored to be used within a few hours before competition.…”

United States Pharmacopeia (USP) Safety Review of Gamma-Aminobutyric Acid (GABA)

“…Because GABA is a key neurotransmitter in the CNS, it is important to understand how much of the administered amount may traverse the blood-brain barrier (BBB) when it is ingested orally as a dietary supplement. So far, evidence indicates that very low amounts of GABA cross from the plasma into the brain through the BBB even when GABA is exogenously administered orally or intravenously [ 97 , 98 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ].…”