Pharmacology, pharmacokinetics, and behavioral effects of caffeine in horses.

Caffeine (4 mg/kg) was given by rapid IV injection to 4 horses. Plasma concentrations of the drug peaked at 10 micrograms/ml and decreased rapidly at first, and then more slowly, with an apparent beta-phase half-life of 18.2 hours. Urinary concentrations of caffeine were remarkably consistent at about 3 times plasma values of the drug. Caffeine was detectable in both plasma and urine of the horses for up to 9 days after dosing. After oral administration, caffeine was absorbed poorly with an apparent bioavailability of 39%. Although blood concentrations of caffeine peaked rapidly after oral administration, its apparent plasma half-life by this route was about 42 hours. These observations identify the possible existence of a slowly absorbed pool of caffeine in the gastrointestinal tract after oral administration. When caffeine-treated horses were given fentanyl, the locomotor response to fentanyl was enhanced. This potentiation of the fentanyl response peaked at between 0 and 4 hours after dosing and was gone by 72 hours after caffeine dosing. The data indicate that the probability of behavioral stimulation due to caffeine by 72 hours after dosing may be small.