The impact of transdermal application site on pharmacokinetics and selected pharmacodynamics of buprenorphine in horses.

Overview

• This study evaluated how the site of transdermal application of buprenorphine affects its absorption, plasma levels, and pain-relief effects in horses.
• It found that applying buprenorphine to the neck at a specific dose produced effective pain relief with minimal side effects.

Study Objectives and Hypothesis

• The primary goal was to assess how the location of transdermal buprenorphine application influences:
• Drug absorption and plasma concentrations
• Physiological responses
• Behavioral and antinociceptive (pain-blocking) effects
• The researchers hypothesized that both the dose and site of administration would affect these outcomes in horses.

Study Design and Methods

• The research was conducted in two parts:
• Study 1: A prospective, randomized, three-way crossover design with 6 horses aged 3-14 years
• Study 2: A single-dose experimental study with 8 horses aged 3-14 years
• In Study 1:
• A single dose of buprenorphine (45 µg/kg) was applied transdermally to three different locations: the neck, croup (hindquarters), and stifle (knee area)
• Blood samples were taken at set time points to measure plasma buprenorphine concentrations
• At the end, a skin biopsy was collected to assess local drug concentration
• In Study 2:
• A higher dose (90 µg/kg) was applied to the neck, as this site showed promising results in Study 1
• Blood samples were collected and analyzed for plasma buprenorphine concentration using liquid chromatography-tandem mass spectrometry
• Pharmacokinetic analysis was performed to understand absorption, distribution, and duration of the drug in circulation
• Behavioral and physiological responses were monitored before and after dosing
• Antinociceptive effect was evaluated by measuring thermal threshold latency — how long it took for horses to feel heat-induced pain stimuli
• Statistical analysis included mixed effects ANOVA to compare pharmacodynamic parameters at baseline and after treatment.

Key Results

• Plasma drug concentrations:
• Highest concentrations were observed when buprenorphine was applied to the neck and stifle compared to the croup
• Antinociceptive effect:
• Applying 90 µg/kg to the neck increased the thermal nociceptive threshold significantly from 3 hours post-application and lasted up to 36 hours
• This effect corresponded to plasma buprenorphine levels ≥ 0.1 ng/mL, indicating a concentration-effect relationship
• Safety and side effects:
• Minimal changes were observed in locomotor activity, heart rate, and gut sounds (borborygmi), suggesting low adverse effects

Conclusions and Implications

• The study demonstrated that:
• Transdermal buprenorphine can provide measurable pain relief in horses
• The site of application significantly influences drug absorption and effectiveness
• The neck is the optimal application site among those tested
• The selected dose of 90 µg/kg achieved effective thermal antinociception with minimal side effects
• This method of analgesic delivery could be useful for managing pain in horses non-invasively over extended periods.