Cardiopulmonary, behavioral, and pharmacokinetic effects of propoxyphene in horses

The acute behavioral cardiopulmonary and pharmacokinetic effects of propoxyphene hydrochloride were studied in seven adult horses. Each horse was given three different dosages of propoxyphene (0.5, 1.0, 2.2 mg/kg) IV. Fourteen days was allotted between each drug administration. The lower IV dosages of propoxyphene (0.5, 1.0 mg/kg) resulted in no changes in indices of cardiopulmonary function. Four horses demonstrated a transient period of muscle fasciculations when given 0.5 mg of propoxyphene/kg. Horses given 1.0 mg/kg demonstrated a brief period of euphoria, ataxia, and muscle fasciculations followed by a period of increased motor activity lasting for approximately 30 minutes. Horses given 2.2 mg of propoxyphene/kg demonstrated significant (P less than 0.05) increases in heart rate and arterial blood pressure and, after a brief period of ataxia and disorientation, displayed increased motor and locomotor activity lasting several hours. These behavioral effects were less apparent in three of four horses 4 hours after their appearance by the IV administration of naloxone. Propoxyphene exhibited a dose dependent half-life of from 61 to 135 minutes and an apparent volume of distribution of from 2.54 to 4.26 L/kg. Total body clearance was 21.9-28.4 ml/min/kg. In the adult pain-free horse, propoxyphene causes dose dependent excitatory effects similar to the narcotic analgesics.