Drug metabolism in the horse: a review

Abstract

A detailed understanding of equine drug metabolism is important for detection of drug abuse in horseracing and also in veterinary drug development and practice. To date, however, no comprehensive review of equine drug metabolism has been published. The majority of literature regarding equine drug metabolite profiles is derived from sports drug detection research and is generally targeted at detecting marker metabolites of drug abuse. However, the bulk of the literature on equine drug metabolism enzymology is derived from veterinary studies aimed at determining the molecular basis of metabolism. In this article, the phase 1 and 2 metabolisms of seven of the most important classes of drugs monitored in horseracing are reviewed, including: anabolic-androgenic steroids (AAS), β₂ -agonists, stimulants, sedatives/tranquilizers, local anesthetics, non-steroidal anti-inflammatory analgesics (NSAIDS)/cyclooxygenase-2 (COX-2) inhibitors, and opioid analgesics. A summary of the literature relating to the enzymology of drug metabolism in this species is also be presented. The future of equine drug metabolism in the area of doping research will be influenced by several factors, including: a possible move towards the increased use of blood and other alternative testing matrices; the development of assays based on intact drug conjugates; the increasing threat of 'designer' and herbal- based products; advances in the use of in vitro technologies; the increased use of liquid-chromatography/high-resolution mass spectrometry; and the possibility of screening using 'omics' approaches. Also, the recent cloning of a range of equine cytochrome P450 (CYP) enzymes opens up the potential for carrying out more detailed mechanistic pharmacological and toxicological veterinary studies.

Inhibition of in vitro metabolism of testosterone in human, dog and horse liver microsomes to investigate species differences

“…In contrast, in humans the 3-keto steroid reductase forms 3a-metabolites, whereas horses are prone to form 3b isomers. Furthermore, testosterone 6-hydroxylation is less significant in horses compared to humans (Scarth et al, 2011).…”

Characterization of In Vitro Synthesized Equine Metabolites of the Selective Androgen Receptor Modulators S24 and S4

“…In case of suspected abuse, it is obligatory to confirm the presence of a substance by comparison with authentic reference material. According to International Laboratory Accreditation Cooperation-G7 guidelines, it is valid to use enzymatically synthesized reference material for this purpose [11], which is of great advantage in cases where adequate reference compounds are not commercially available.…”

Challenges in detecting substances for equine anti‐doping

“…[2] Stimulants affect central nervous system, increase the psychomotoric activity and eliminate the sense of fatigue, as well as enhance the cardiovascular or muscular function by affecting the sympathetic nervous system. [73] The detection of parent compounds and/or their metabolites is accomplished by the complementary use of GC-MS and LC-MS. This approach, however, is inadequate when dealing with designer stimulants, where reference materials are not available.…”