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

Heather K Knych, S. J. Steinmetz, D. S. Mckemie

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume38
Issue number2
DOIs
StatePublished - Apr 1 2015

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gamma-aminobutyric acid
pharmacology
gamma-Aminobutyric Acid
pharmacokinetics
Horses
Pharmacokinetics
horses
dosage
mouth
intravenous injection
Intravenous Administration
oral administration
Oral Administration
urine
Urine
GABA Receptors
sedatives
Plasma Volume
Anti-Anxiety Agents
cerebrospinal fluid

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

Cite this

Endogenous concentrations, pharmacokinetics, and selected pharmacodynamic effects of a single dose of exogenous GABA in horses. / Knych, Heather K; Steinmetz, S. J.; Mckemie, D. S.

In: Journal of Veterinary Pharmacology and Therapeutics, Vol. 38, No. 2, 01.04.2015, p. 113-122.

Research output: Contribution to journalArticle

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