Determination of the highest no‐effect dose (HNED) and of the elimination pattern for cocaine in horses

Abstract

Cocaine is one of the most widespread illegal stimulants utilized by the human population throughout the world. The aim of this study was to establish the highest no-effect dose (HNED) of cocaine on the spontaneous locomotor activity (SLA) of horses in a behavior chamber, and thereby to determine the maximal acceptable threshold of the urinary drug concentration in horses. Twelve English thoroughbred mares received 0.02, 0.03, 0.04, 0.08 or 0.12 mg kg(-1) cocaine i.v. or saline solution (control). It was noted that doses above 0.04 mg kg(-1) induced a significant increase in SLA (P < 0.05, Tukey's test). No significant increase in SLA was seen in the mares that received 0.03 mg kg(-1), but the animals showed important behavioral changes that did not occur after the 0.02 mg kg(-1) dose. It was concluded that the HNED of cocaine for horses in a behavior chamber is 0.02 mg kg(-1). After injection of this dose in five horses, urine samples were collected at predetermined intervals through vesical catheterization. The concentrations of cocaine, norcocaine, benzoylecgonine and ecgonine methyl ester were quantified by liquid chromatography/electrospray ionization tandem mass spectrometry. Cocaine and norcocaine concentrations remained consistently below the level of detection. Benzoylecgonine reached a mean (+/- SEM) maximum concentration of 531.9 +/- 168.7 ng ml(-1) after 4 h, whereas ecgonine methyl ester peaked 2 h after injection at a concentration of 97.2 +/- 26.5 ng ml(-1). The maximum admissible concentration for cocaine and/or metabolites in the urine of horses is difficult to establish unequivocally because of the substantial individual variation in the drug elimination pattern observed in horses, which can be inferred by the large standard error of the means obtained.

Detection and quantification of cocaine metabolites in urine samples from horses administered cocaine

“…It is also possible that this decrease in heart rate was actually related to the alcohol vehicle in which the cocaine was dissolved, as no vehicle control was included in the study. These results are notably different from those obtained by Queiroz‐Neto et al ., who found that intravenous doses as small as 0.03 mg/kg (approximately 15 mg for a 500 kg horse) produced notable, albeit subjective, behavioral changes, such as head tossing and neighing. Although the behavioral assessments in the present study were also subjective, the lack of any prolonged effect on heart rate following administration of the 50 mg dose of cocaine was consistent with a lack of behavioral effects, as one would generally expect some increase in heart rate to be associated with any significant degree of CNS stimulation.…”

“…These findings are consistent with a recent study that indicated that a 10 mg dose of cocaine administered i.v. resulted in quantifiable concentrations of BZE by LC–MS analysis in urine samples collected 24 h after administration (Queiroz‐Neto et al. , 2002).…”

“…Cocaine has been shown to increase the respiratory rate and locomotor activity of horses and a 200 mg intravenous dose increased the maximum run time of horses completing an incremental treadmill exercise test by approximately 15% (McKeever et al. , 1993; Queiroz‐Neto et al. , 2002).…”

“…For example, it is possible that the metabolites are the result of intentional administrations of cocaine and represent attempts to alter the horses' performances. Cocaine has been shown to increase the respiratory rate and locomotor activity of horses and a 200 mg intravenous dose increased the maximum run time of horses completing an incremental treadmill exercise test by approximately 15% (McKeever et al, 1993;Queiroz-Neto et al, 2002). However, it has also been proposed that these cocaine metabolites could be the result of inadvertent contamination by human cocaine abusers who handle or feed the horse.…”

Comparação dos efeitos da romifidina e de uma emulsão de amitraz na sedação e na atividade locomotora espontânea de eqüinos

“…Logan, UT-USA) connected to a computer. 19 SLA was calculated from data registered in the computer as the mean of interruptions every 10 minutes.…”