Pharmacokinetics and behavioral effects of methylphenidate in Thoroughbred horses

In horses given (rapid IV) methylphenidate (Ritalin, alpha-phenyl-2-piperidinacetic acid methyl ester; 0.70 mg/kg), plasma concentrations of the drug decreased rapidly at first, with an apparent alpha half-life of about 19 minutes, and then more slowly, with an apparent beta half-life of about 2.4 hours. These data were well fitted by a 2-compartment open model. In blood, about 40% of the methylphenidate present was in the plasma fraction, and of this, about 80% was plasma-protein bound. If given by subcutaneous or IM injection, plasma concentrations of methylphenidate peaked in about 1 hour and were no longer detectable (cleared) from plasma by 6 hours. Urinary clearance time, however, was longer, and between 12 and 24 hours should be allowed for a dose of methylphenidate to "clear" from urine. Using a variable-interval responding apparatus, methylphenidate was shown to stimulate the responding rate of horses up to 6 times above base line, making it the most potent central stimulant tested in this responding apparatus to date. Peak central stimulation at 30 minutes after IV dosing was seen in horses given 0.4 to 1.0 mg of methylphenidate/kg.