Pharmacology of Procaine in the Horse: Pharmacokinetics and Behavioral Effects

Abstract

SUMMARY After rapid intravenous injection of procaine HCl (2.5 mg/kg of body weight) in Thoroughbred mares, plasma levels of this drug decreased rapidly (t½ α = 5.5 minutes) and then more slowly (t½ β = 50.2 minutes). These kinetics were well fitted by a 2-compartment open model (model I). This model gave an apparent Vd β for procaine in the horse of about 6.7 L/kg of body weight. Since procaine was about 45% bound to equine plasma protein, this gave a true Vd β for procaine of about 12.4 L/kg. After subcutaneous injection of procaine (3.3 mg/kg), plasma levels peaked at 400 ng/ml and then decreased with a half-life of about 65 minutes. These data were well fitted by model I when it was modified to include simple. 1st-order absorption (k = 0.048 minutes −1 ) from the subcutaneous injection site (model II). After intramuscular injection of procaine penicillin (33,000 iu /kg), plasma levels peaked at about 270 ng/ml and then decreased with a half-life of about 600 minutes. These data were approximately fitted by model II assuming a 1st-order rate constant for absorption of procaine of 0.0024 minutes −1 . After intramuscular injection of procaine HCl (10 mg/kg), plasma levels of procaine peaked rapidly at about 600 ng/ml but decreased slowly (t½ = 125 minutes). A satisfactory pharmacokinetic model for this data could not be developed. An approximation of these data was obtained by assuming the existence of 2 intramuscular drug compartments, one containing readily-absorbable drug and the other poorly-absorbable drug (model III). After intraarticular administration of procaine (0.33 mg/kg), plasma levels of this drug peaked at about 24 ng/ml and then decreased with a half-life of about 97 minutes. These data were not modeled. Absorption of the drug was essentially complete by all routes, since dose-corrected areas under the plasma level curves were all comparable. Intravenous infusion of procaine showed that behavioral excitation due to procaine commenced at plasma levels of 600 ng/ml, with horses becoming uncontrollable at plasma levels of about 1,500 ng/ml. These plasma procaine levels are about one-twentieth of those associated with central nervous system excitation in human beings. Horses are thus at least 20-fold more sensitive to the central stimulant action of procaine than are human beings.