Pharmacokinetic-pharmacodynamic modelling of intravenous buprenorphine in conscious horses.

The study investigates the pharmacokinetics and pharmacodynamics of buprenorphine in horses, specifically examining its effectiveness for peri-operative analgesia. It found that buprenorphine concentrations in the bloodstream were detectable for extended periods post-administration, and the drug increased thermal and mechanical thresholds, indicative of pain relief.

Research Objectives and Methods

• The study aimed to understand the pharmacokinetics (the movement of drugs within the body) of buprenorphine and its metabolite norbuprenorphine in horses, and connect these parameters with the drug’s pharmacodynamic effects (the biological and physiological effects of the drug).
• To achieve this, six research horses were involved in a single phase, non-blinded study.
• All horses were given a single intravenous (IV) dose of buprenorphine and the effects were measured at multiple time points post administration.
• Physiological parameters such as heart and respiratory rates, gastrointestinal motility, and locomotor activity were observed. Pain thresholds (both thermal and mechanical) were also recorded.
• Blood samples were taken at various time intervals to monitor plasma concentrations of buprenorphine and norbuprenorphine using a specialized analytical technique called liquid chromatography-tandem mass spectroscopy (LC-MS/MS).
• A non-compartmental model was applied for analysis of the resulting data and buprenorphine concentrations were mapped against changes in thermal and mechanical thresholds.

Findings and Conclusions

• The results showed that buprenorphine could be detected in the plasma of all horses up to 480 minutes (8 hours) post administration. In two horses, it remained detectable until 720 minutes (12 hours).
• There was no detection of norbuprenorphine, which is a metabolite of buprenorphine.
• Recognizable changes in thermal and mechanical pain thresholds were marked from 15 minutes onwards post administration, continuing to 8-12 hours. This indicates the analgesic (pain-relieving) effect of buprenorphine.
• The researchers concluded that their findings support the use of buprenorphine for peri-operative (around the time of surgery) pain relief in horses.