Pharmacokinetics, pharmacodynamics and antinociceptive effects of buprenorphine following transdermal administration to horses.

This research investigates how a transdermal solution of buprenorphine, a painkiller, is absorbed and affects horses when applied onto their skin, in comparison with traditional intravenous administration. Although the study found that the drug does get absorbed into the horse’s system through the skin to an extent, it did not produce consistently effective pain relief.

Study Design

• This was a prospective nonrandomized four-part parallel experimental study, which took a group of eight horses, aged between 6-12 years, as subjects.
• The horses were administered varying doses of 15, 30 and 45 μg kg of buprenorphine transdermal solution in different instances, each separated with a 2 week washout period. An additional dose of 5 μg kg of buprenorphine was given intravenously for comparison.

Measurement and Analysis

• Buprenorphine concentrations in the horse’s system were measured via liquid chromatography-tandem mass spectrometry and analysed using a nonlinear mixed effects population pharmacokinetic model. This would allow the scientists to determine how the drug was absorbed, distributed, metabolised and excreted from the horse’s system.
• Pharmacodynamic effects were also evaluated. These included changes in the horse’s locomotor activity, heart rate, body temperature, gastrointestinal sounds (borborygmi) and response to thermal and mechanical pain (nociceptive thresholds).
• A statistical method called mixed effects analysis of variance was performed to identify any changes in pharmacodynamic parameters between baseline measurements and those taken at specific time points. The horse’s responses in the different dose groups were also compared.

Findings

• The application of buprenorphine onto the horse’s skin (transdermal) resulted in overall lower systemic concentrations of the drug, when compared to intravenous (IV) injection. The bioavailability, or the amount of drug that was effectively absorbed into the horse’s system, was just 11% for the transdermal solution.
• Antinociceptive (pain relieving) effects, as evaluated through thermal pain thresholds, were consistently observed following IV injection, but were only sporadic in the groups where the drug was given via transdermal application. This is likely due to the lower systemic concentrations that were achieved.
• Changes in locomotor activity, heart rate and gastrointestinal sounds varied with time and the dosage given.

Conclusion and Future Research

• The study concluded that the transdermal application of buprenorphine, even at different doses, had limited success in relieving pain in the horses. This was likely because the absorption of the drug through the skin into the systemic circulation was considerably less when compared to direct intravenous administration.
• The authors suggest that future studies could further investigate the antinociceptive effects of administering higher transdermal doses, or applying the drug at different sites. The aim would be to aid in developing more effective and practical methods for providing horses with pain relief.