Cardiopulmonary, behavioral, and pharmacokinetic effects of propoxyphene in horses.

This research paper investigates the effects of different doses of the drug propoxyphene on adult horses, focusing on changes in behavior, heart and lung function and drug metabolism. The findings show that the drug can cause significant increases in both heart rate and blood pressure, along with increased movement and behavioral changes, dependent on the dose administered.

Study Methodology

• The study was conducted on seven adult horses who were given propoxyphene hydrochloride in three different dosages—0.5 mg/kg, 1.0 mg/kg and 2.2 mg/kg—via an intravenous (IV) administration.
• A break of two weeks was given between each drug administration to clear any residual drug in the horse’s system.

Findings: Cardiopulmonary Effects

• The lower dosages (0.5 mg/kg and 1.0 mg/kg) did not result in any changes in the heart and lung function of the horses.
• The highest dosage (2.2 mg/kg) led to significant increases in heart rate and arterial blood pressure.

Findings: Behavioral Effects

• At a 0.5 mg/kg dose, four horses showed short-lived muscle convulsions.
• At a 1.0 mg/kg dose, the horses displayed a brief period of euphoria, unsteady gait, and muscle convulsions, followed by a period of increased activity lasting about 30 minutes.
• Horses administered with a 2.2 mg/kg dose after a brief period of unsteady gait and confusion, demonstrated increased movement and activity lasting several hours.
• The behavioral effects were less noticeable in three of four horses four hours after the appearance of these effects and after the administration of naloxone (a drug that reverses effects of opioid medicines).

Findings: Pharmacokinetics of Propoxyphene

• Propoxyphene showed a dose-dependent half-life ranging from 61 to 135 minutes. The term “half-life” refers to the time taken for the body to eliminate half of the drug.
• The apparent volume of distribution of the drug was between 2.54 and 4.26 L/kg. The volume of distribution refers to the theoretical space in the body in which a drug is dispersed and influences the potency and duration of a drug’s pharmacologic action.
• The total body clearance rate was 21.9-28.4 ml/min/kg, referring to the volume of plasma from which the drug is completely cleared in a given time period.

Conclusion

• In horses that are free from pain, propoxyphene causes dose-dependent excitatory effects similar to narcotic painkillers.