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

Abstract: To assess absorption after transdermal application of buprenorphine to different sites and assess behavioral, antinociceptive and adverse effects. It was hypothesized that the dose and site of transdermal buprenorphine administration would influence absorption, plasma drug concentrations, physiological, antinociceptive and behavioral effects in horses. Methods: Two-part study; prospective randomized balanced three-way crossover (study 1) and single-dose (study 2) experimental study. Methods: Six (study 1) and eight (study 2) horses, aged 3-14 years. Methods: In study 1, horses were administered a single dose of buprenorphine (45 μg kg), applied to the neck, croup and stifle. Blood samples were collected at fixed time points and a skin biopsy taken at the final time point for buprenorphine concentration analysis. In study 2, horses were administered a single transdermal dose of buprenorphine (90 μg kg) applied to the neck (determined in study 1). Blood samples were collected and buprenorphine concentrations determined by liquid chromatography-tandem mass spectrometry, and pharmacokinetic analysis performed. Pre- and post-drug-related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat. Mixed effects analysis of variance comparisons were performed to assess differences in pharmacodynamic parameters between baseline and each time point. Results: Plasma buprenorphine concentrations were highest after application to the neck and stifle. Transdermal application of 90 μg kg to the neck significantly (p < 0.05) increased thermal nociceptive thresholds from 3 hours and up to 36 hours after application. This corresponded with plasma buprenorphine concentrations ≥ 0.1 ng mL. Changes in locomotor activity, heart rate and borborygmi were minimal. Conclusions: A thermal antinociceptive effect was observed after the transdermal delivery of 90 μg kg of buprenorphine, applied to the neck.