After intravenous (i.v.) injection, acepromazine was distributed widely in the horse (Vd = 6.6 litres/kg) and bound extensively (greater than 99%) plasma proteins. Plasma levels of drug declined with an alpha half-life of 4.2 min, while the beta phase or elimination half-life was 184.8 min. At a dosage level of 0.3 mg/kg acepromazine was detectable in the plasma for 8 h post dosing. The whole blood partitioning of acepromazine was 46% in the plasma phase and 54% in the erythrocyte phase. Penile prolapse was clearly evident at doses from 0.01 mg/kg to 0.4 mg/kg i.v., and the duration and extent of protrusion were dose related. Hematocrit levels were significantly lowered by administration of 0.002 mg/kg i.v. (about 1 mg to a 500 kg horse) and increasing dosages resulted in greater than 20% lowering of the hematocrit from control levels. Pretreatment of horses with acepromazine also reduced the variable interval (VI 60) responding rate in all horses tested. These data show that hematocrit changes are the most sensitive pharmacological responses to acepromazine, followed by changes in penile extension, respiratory rate, VI responding and locomotor responses. Acepromazine is difficult to detect in plasma at normal clinical doses. However, because of its large volume of distribution, its urinary elimination is likely prolonged, and further work on its elimination in equine urine is required.

Recoveries of acepromazine and chlorpromazine from equine plasma were examined. Recoveries of both drugs from plasma were poor under theoretically optimal conditions for basic drugs. When a wide range of extraction pH was examined, it was found that more complete recoveries of these drugs from plasma were achieved at pH 5-6. Use of [3H] chlorpromazine showed that the rate of migration of the drug from an aqueous to a nonpolar environment was much faster at pH 6.0 than at pH 9.2 from both plasma and buffer solutions. Times required for equilibration with agitation were 15 min at pH 6.0, 1 h at pH 9.2, and 2 h at pH 11.0. With these agitation times and pH values, recoveries were more than 95% complete.