Acepromazine pharmacokinetics: a forensic perspective.
Abstract: Acepromazine (ACP) is a useful therapeutic drug, but is a prohibited substance in competition horses. The illicit use of ACP is difficult to detect due to its rapid metabolism, so this study investigated the ACP metabolite 2-(1-hydroxyethyl)promazine sulphoxide (HEPS) as a potential forensic marker. Acepromazine maleate, equivalent to 30mg of ACP, was given IV to 12 racing-bred geldings. Blood and urine were collected for 7days post-administration and analysed for ACP and HEPS by liquid chromatography-mass spectrometry (LC-MS). Acepromazine was quantifiable in plasma for up to 3h with little reaching the urine unmodified. Similar to previous studies, there was wide variation in the distribution and metabolism of ACP. The metabolite HEPS was quantifiable for up to 24h in plasma and 144h in urine. The metabolism of ACP to HEPS was fast and erratic, so the early phase of the HEPS emergence could not be modelled directly, but was assumed to be similar to the rate of disappearance of ACP. However, the relationship between peak plasma HEPS and the y-intercept of the kinetic model was strong (P=0.001, r(2)=0.72), allowing accurate determination of the formation pharmacokinetics of HEPS. Due to its rapid metabolism, testing of forensic samples for the parent drug is redundant with IV administration. The relatively long half-life of HEPS and its stable behaviour beyond the initial phase make it a valuable indicator of ACP use, and by determining the urine-to-plasma concentration ratios for HEPS, the approximate dose of ACP administration may be estimated.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication Date: 2012-04-23 PubMed ID: 22534188DOI: 10.1016/j.tvjl.2012.03.017Google Scholar: Lookup
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- Clinical Trial
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article focuses on the analysis of Acepromazine (ACP) and its metabolite, 2-(1-hydroxyethyl)promazine sulphoxide (HEPS), in horse samples. The article examines how HEPS could be a potential forensic marker due to ACP’s quick metabolism and difficulty to detect.
Investigation of ACP and HEPS
- The study aimed to explore the metabolism of the therapeutic drug Acepromazine (ACP) in competition horses, an area where its use is prohibited. The researchers were interested in detecting illicit use of the drug, which proves challenging due to its rapid metabolism.
- The study specifically investigated the metabolite of ACP, 2-(1-hydroxyethyl)promazine sulphoxide (HEPS), as a potential marker for forensic identification. Analyzing levels of HEPS as opposed to ACP could provide a more accurate indication of ACP administration.
Methodology
- Acepromazine maleate, equivalent to 30mg of ACP, was given intravenously to 12 competition horses.
- Blood and urine samples were collected over a period of 7 days following the administration.
- The samples were analysed for both ACP and HEPS via liquid chromatography-mass spectrometry (LC-MS).
Findings
- ACP was present in plasma for up to 3 hours and very little of it was found in urine unmodified.
- The metabolite HEPS could be quantified in plasma for up to 24 hours and up to 144 hours in urine.
- The rapid and erratic metabolism of ACP to HEPS meant that the early phase of HEPS emergence could not be directly modelled, but the researchers believed the rate would be similar to the rate of disappearance of ACP.
- A strong relationship was found between peak plasma HEPS and the rate of metabolization, enabling an estimation of formation pharmacokinetics of HEPS.
Conclusions
- The research concluded that due to ACP’s quick metabolism, testing for its presence in samples is not effective.
- Instead, the metabolite HEPS, due to its longer half-life and stable behaviour beyond the initial phase, is a better indication of ACP use.
- By determining the ratio of HEPS concentrations in urine to plasma, it is possible to estimate the approximate dose of ACP administration.
Cite This Article
APA
Schneiders FI, Noble GK, Boston RC, Dunstan AJ, Sillence MN, McKinney AR.
(2012).
Acepromazine pharmacokinetics: a forensic perspective.
Vet J, 194(1), 48-54.
https://doi.org/10.1016/j.tvjl.2012.03.017 Publication
Researcher Affiliations
- School of Animal and Veterinary Sciences, Charles Sturt University, Locked Bag 588, Wagga Wagga, NSW 2678, Australia.
MeSH Terms
- Acepromazine / blood
- Acepromazine / pharmacokinetics
- Acepromazine / urine
- Animals
- Area Under Curve
- Dopamine Antagonists / blood
- Dopamine Antagonists / pharmacokinetics
- Dopamine Antagonists / urine
- Forensic Medicine / methods
- Half-Life
- Horses / blood
- Horses / metabolism
- Male
- Promazine / analogs & derivatives
- Promazine / blood
- Promazine / metabolism
Citations
This article has been cited 2 times.- Kandeel M, Almubarak AI, Hussen J, El-Deeb W, Venugopala KN. Pharmacokinetic, Clinical, and Myeloid Marker Responses to Acepromazine Sedation in Arabian Camels.. Front Vet Sci 2021;8:725841.
- Jaber SM, Hankenson FC, Heng K, McKinstry-Wu A, Kelz MB, Marx JO. Dose regimens, variability, and complications associated with using repeat-bolus dosing to extend a surgical plane of anesthesia in laboratory mice.. J Am Assoc Lab Anim Sci 2014 Nov;53(6):684-91.
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