L‐ and D‐threo ethylphenidate concentrations, pharmacokinetics, and pharmacodynamics in horses

Abstract

Ethylphenidate is a psychostimulant and analog of the commonly prescribed compound, methylphenidate (Ritalin®). There are a limited number of studies describing the disposition and pharmacologic/toxicological effects of ethylphenidate in any species. The abuse potential in equine athletes along with the limited data available regarding administration in horses necessitates further study. The objectives of the current study were to describe drug concentrations, develop an analytical method that could be used to regulate its use, and describe the pharmacodynamic effects of ethylphenidate in horses. To that end, 12 horses were randomized into 3 dose groups (intravenous: 10 mg or 40 mg, oral: 40 mg). Ethylphenidate was administered and blood and urine samples were collected prior to and for up to 72 hours post drug administration. Concentrations of D-threo ethylphenidate and the metabolite ritalinic acid were measured using Liquid Chromatography-tandem Mass Spectrometry. L-threo ethylphenidate concentrations were estimated from D-threo ethylphenidate concentrations. Serum concentrations of ethylphenidate were below detectable levels by 8, 18, and 12 hours following intravenous administration of 10 mg and 40 mg and oral administration of 40 mg, respectively. Ritalinic acid was non-detectable at 72 hours in the group that received a 10-mg intravenous and 40-mg oral dose of ethylphenidate. Ritalinic acid concentrations were below the LOQ at 72 hours following intravenous administration of 40 mg of ethylphenidate. While the number of animals per dose group were small, no stimulatory behavior or significant changes in heart rate were noted. Untoward effects including gastrointestinal adverse effects were noted in all dose groups.

Detection of Methylphenidate in Equine Hair Using Liquid Chromatography–High-Resolution Mass Spectrometry

“…Studies conducted in the 1960s clearly show that methylphenidate administration to horses at doses ranging from ≈0.1 to 1.2 mg/kg have effects on the central nervous system with increases in pulse, respiratory rate, and blood pressure observed [ 3 ]. The absorption, distribution, metabolism, and excretion properties of methylphenidate or structurally similar agents such as ethylphenidate have not been investigated in great detail in the horse, but some studies have shown that these compounds are relatively quickly cleared and primarily excreted in urine following intramuscular, intravenous, or oral administrations [ 3 , 4 , 5 ]. The major metabolite of methylphenidate in humans is ritalinic acid.…”

“…The detection and confirmation of methylphenidate in urine and blood samples is challenging due to its rapid distribution and elimination half-lives, its metabolism to ritalinic acid, and the higher background of its major product ion (84 m / z ), which makes low-level detection challenging [ 3 , 4 , 5 ]. Analysis of hair samples offers an alternative sampling matrix that can extend the potential detection window following the administration of a prohibited substance [ 7 ].…”