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: 10mg or 40mg, oral: 40mg). Ethylphenidate was administered and blood and urine samples were collected prior to and for up to 72hours 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 12hours following intravenous administration of 10mg and 40mg and oral administration of 40mg, respectively. Ritalinic acid was non-detectable at 72hours in the group that received a 10-mg intravenous and 40-mg oral dose of ethylphenidate. Ritalinic acid concentrations were below the LOQ at 72hours following intravenous administration of 40mg 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.