Pharmacokinetics and selected pharmacodynamics of romifidine following low-dose intravenous administration in combination with exercise to quarter horses.

Romifidine is an alpha-2 adrenergic agonist used for sedation and analgesia in horses. As it is a prohibited substance, its purported use at low doses in performance horses necessitates further study. The primary goal of the study reported here was to describe the serum concentrations and pharmacokinetics of romifidine following low-dose administration immediately prior to exercise, utilizing a highly sensitive liquid chromatography-tandem mass spectrometry assay that is currently employed in many drug testing laboratories. An additional objective was to describe changes in heart rate and rhythm following intravenous administration of romifidine followed by exercise. Eight adult Quarter Horses received a single intravenous dose of 5 mg (0.01 mg/kg) romifidine followed by 1 h of exercise. Blood samples were collected and drug concentrations measured at time 0 and at various times up to 72 h. Mean ± SD systemic clearance, steady-state volume of distribution and terminal elimination half-life were 34.1 ± 6.06 mL/min/kg and 4.89 ± 1.31 L/kg and 3.09 ± 1.18 h, respectively. Romifidine serum concentrations fell below the LOQ (0.01 ng/mL) and the LOD (0.005 ng/mL) by 24 h postadministration. Heart rate and rhythm appeared unaffected when a low dose of romifidine was administered immediately prior to exercise.

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

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.

Detection, pharmacokinetics and cardiac effects following administration of clenbuterol to exercised horses.

REASONS FOR PERFORMING STUDY: The use of clenbuterol in performance horses necessitates the establishment of appropriate withdrawal times. OBJECTIVES: To describe plasma and urine concentrations of clenbuterol following administration of 2 commonly used dosing regimens to racing fit Thoroughbreds. STUDY DESIGN: Experimental. METHODS: Twenty-two horses received an oral dose of 0.8 µg/kg bwt of clenbuterol twice daily for 30 days. A second group of 6 horses received clenbuterol according to the escalating dose protocol on the manufacturer's label. Blood and urine samples were collected prior to, throughout and at various times up to 35 days post administration of the final dose. Drug concentrations were measured using liquid chromatography-mass spectrometry, and plasma data were analysed using noncompartmental analysis. Behavioural and physiological effects were monitored and heart rate was recorded throughout the course of the study. RESULTS: Clenbuterol plasma concentrations were below the limit of quantification (10 pg/ml) of the assay by Day 4 in all horses receiving the chronic low-dose regimen and by Day 7 in 5 of 6 horses receiving the escalating dosing protocol. Urine clenbuterol concentrations fell below the limit of quantification of the assay between Days 21 and 28 in all 22 horses in the low-dose group and in 5 of 6 of the horses in the escalating dose group. Muscle fasciculations, sweating and transient increases in heart rate were noted in a small number of horses following clenbuterol administration, but tolerance to these effects occurred rapidly. CONCLUSIONS AND POTENTIAL RELEVANCE: Establishment of appropriate withdrawal times for specific racing jurisdictions depends upon the threshold adopted by that specific jurisdiction. This study extends previous studies describing the pharmacokinetics of clenbuterol and describes plasma and urine concentrations following administration of 2 commonly used dosing regimens to racing fit Thoroughbreds, which will allow jurisdictions to establish withdrawal times in order to prevent inadvertent positive regulatory findings.