Pharmacokinetics of Ethyl Glucuronide and Ethyl Sulfate and Pharmacodynamic Effects Following Intravenous and Oral Administration of Ethanol to Exercised Horses

Ethanol, a central nervous system depressant and banned substance in horseracing, has reportedly been administered to horses prior to competition to "calm a horse's nerves." In this study, the pharmacokinetics of two metabolites of ethanol were studied to better understand the behavior of this compound in the horse and provide a scientific basis for regulation of its administration. Six horses received a single intravenous (30 mL; 1200 mg) and oral (90 mL; 3600 mg) administration of ethanol (vodka, 40% ABV) in a balanced cross-over design. Blood and urine samples were collected at various times post administration for up to 24 h. Concentrations of ethyl glucuronide and ethyl sulfate were determined using liquid chromatography-tandem mass spectrometry and pharmacokinetic analysis performed. Behavioral, locomotor activity and effects on heart rate were assessed. The maximum concentration (mean +/- SD) of ethyl glucuronide was 71.5 +/- 42.7 and 105.0 +/- 47.5 ng/mL at 0.88 h following IV and oral administration, respectively. The maximum concentrations for the ethyl sulfate metabolite following IV and oral administration were 1.61 +/- 0.60 and 3.46 +/- 1.68 ng/mL, respectively. Urine concentrations of both metabolites were non-detectable by 24 h post ethyl alcohol administration. No observable behavioral responses were noted following IV or oral administration. Significant decreases in heart rate were noted at various times starting at 10 min until 4 h post administration in the oral dose group. Both ethyl glucuronide and ethyl sulfate could be useful markers for detection of illicit administration of ethanol to horses. This study describes the pharmacokinetics of ethanol metabolites following intravenous and oral administration to horses. Based on rapid metabolism, ethyl glucuronide is the best candidate for monitoring of illicit administration to performance horses. Notable pharmacodynamic responses included a decrease in heart rate following oral administration.image