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.
Copyright 2002 John Wiley & Sons, Ltd.
Publication Date: 2002-03-29 PubMed ID: 11920936DOI: 10.1002/jat.836Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study aimed to determine the highest dose of cocaine that would not affect a horse’s spontaneous locomotor activity (SLA), and to observe cocaine’s elimination pattern in horses’ bodies.
Plain Language Overview
This research studied the maximum dose of cocaine that wouldn’t affect the spontaneous movements of horses. It also examined how horses’ bodies get rid of cocaine and its metabolites, and found wide variations among individual horses.
Objective of the Research
- The key objective was to ascertain the Highest No-Effect Dose (HNED) of cocaine — the maximum dose that does not result in a significant change in the spontaneous locomotor activity (SLA) of horses.
- The study also aimed to identify the upper permissible limit of cocaine concentration in horses’ urine.
- Finally, the research set out to understand the elimination pattern of cocaine and its metabolites in horses.
Methodology
- Twelve English Thoroughbred mares were administered varying doses of cocaine intravenously, or a saline solution as a control.
- The highest dose that did not elicit significant changes in their SLA or behaviour was identified as the HNED.
- Next, urine samples were collected from a subgroup of five horses at predetermined intervals after injecting the HNED.
- These samples were then analyzed using liquid chromatography/electrospray ionization tandem mass spectrometry to determine the concentrations of cocaine and its metabolites.
Results
- The HNED of cocaine for horses was found to be 0.02 mg kg(-1) in a behavior chamber setup.
- Cocaine and norcocaine were consistently undetectable in the horses’ urine.
- Two metabolites of cocaine, benzoylecgonine and ecgonine methyl ester, peaked at 4 hours and 2 hours after injection respectively.
- Despite achieving the above results, determining a maximum admissible concentration for cocaine or its metabolites in horse urine is reported as challenging due to considerable individual variation in the horses’ drug elimination patterns.
Cite This Article
APA
Queiroz-Neto A, Zamur G, Lacerda-Neto JC, Tobin T.
(2002).
Determination of the highest no-effect dose (HNED) and of the elimination pattern for cocaine in horses.
J Appl Toxicol, 22(2), 117-121.
https://doi.org/10.1002/jat.836 Publication
Researcher Affiliations
- Departamento de Morfologia e Fisiologia Animal, Faculdade de Ciências Agrárias e Veterinárias, Campus de Jaboticabal, FCAV/UNESP, 14884-900 Jaboticabal, SP, Brazil. aqueiroz@fcav.unesp.br
MeSH Terms
- Animals
- Behavior, Animal / drug effects
- Biotransformation
- Chromatography, Liquid / veterinary
- Cocaine / administration & dosage
- Cocaine / analogs & derivatives
- Cocaine / metabolism
- Cocaine / toxicity
- Cocaine / urine
- Dose-Response Relationship, Drug
- Female
- Horses
- Injections, Intravenous
- Kinetics
- Locomotion / drug effects
- No-Observed-Adverse-Effect Level
- Spectrometry, Mass, Electrospray Ionization / veterinary
Citations
This article has been cited 1 times.- Oster E, Čudina N, Pavasović H, Prevendar Crnić A, Božić F, Fadel C, Giorgi M. Intoxication of dogs and cats with common stimulating, hallucinogenic and dissociative recreational drugs.. Vet Anim Sci 2023 Mar;19:100288.
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