Elimination of doxepin isomers from the horse following intravenous application.

The researchers developed a method to analyze the presence of the tricyclic antidepressant doxepin in horses, which is often used illicitly to tranquilize racing horses. They assessed the way the drug gets eliminated from the horse’s system and made recommendations on the most effective ways to screen for it.

Study Objectives

• The main goal of the study was to develop a dependable method to monitor and analyze the presence of doxepin, a tricyclic antidepressant, in horses. Doxepin has been associated with the illegal medication of racing horses and hence needs to be screened for anti-doping purposes.
• Since no documented methods existed for analyzing doxepin in horse body fluids, the researchers aimed to create a highly sensitive analytical tool using gas chromatography/mass spectrometry.

Methodology and Findings

• A dose of 1 mg doxepin-HCl/kg was administered intravenously to horses (n=4). Both doxepin isomers, trans- and cis-, were quantified up to 24 hours in horse serum.
• The researchers found that the beta half-lives of the trans- and cis-isomers were 3.5 and 3.1 hours, respectively.
• The ratio of the trans/cis-isomers remained constant (4.7:1) during the drug elimination and corresponded to the original composition of the antidepressant.
• Low concentrations of the trans-isomer were detected in the urine of the horses for up to 12 hours post-administration, while the cis-isomer was only found in two of the four horses for up to 8 and 12 hours.
• In comparison to urine levels, the mean trans-isomer concentrations in the serum were 120-fold higher after 3 hours and at least sixfold higher after 12 hours.

Conclusion and Recommendations

• The findings demonstrate that the serum of horses exhibits significantly higher concentrations of the doxepin isomers compared to urine. Therefore, it was concluded that when screening for doxepin, the blood of horses is a more recommended body fluid to use.