Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses.
Abstract: Matrix type transdermal buprenorphine patches have not been investigated in horses and may provide an effective means of providing continuous pain control for extended period and eliminating venous catheterization. Unassigned: Assessment of the physiological variables (heart rate, respiratory rate, body temperature) and thermal nociceptive threshold testing, and describing the pharmacokinetic profile of transdermal buprenorphine matrix-type patch (20 μg h and 40 μg h dosing) in healthy adult horses. Unassigned: Randomised experimental study with a Latin-square design. Unassigned: Six adult healthy horses received each of the three treatments with a minimum 10 day washout period. BUP0 horses did not receive a patch (control). BUP20 horses received one patch (20 μg h) applied on the ventral aspect of the tail base resulting in a dose of 0.03-0.04 μg kg h. BUP40 horses received two patches placed alongside each other (40 μg h) on the tail base resulting in a dose of 0.07-0.09 μg kg h. Whole blood samples (for determination of buprenorphine concentration), physiological variables and thermal threshold testing were performed before (0 h) and at 2, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, and 96 h after patch application. The patches were removed 72 h following placement and were analyzed for residual buprenorphine content. Unassigned: Between the three groups, there was no change in physiological variables across timepoints as compared to baseline ( > 0.1). With the higher dose, there was a significant increase in thermal thresholds from baseline values from 2 h until 48 h and these values were significantly higher than the group receiving the lower patch dose for multiple timepoints up to 40 h. 40 μg h patch led to consistent measurable plasma concentrations starting at 2 h up to 96 h, with the mean plasma concentrations of > 0.1 ng/ml from 4 h to 40 h. Unassigned: 20 μg h and 40 μg h patch doses were well tolerated by all horses. At higher dose, plasma buprenorphine concentrations were more consistently measurable and blunted thermal thresholds for 48 h vs. 32 h with 20 μg h dosing as compared to control.
© 2024 Paranjape, Knych, Berghaus, Cathcart, Giancola, Craig, James, Saksena and Reed.
Publication Date: 2024-03-11 PubMed ID: 38529072PubMed Central: PMC10961409DOI: 10.3389/fpain.2024.1373555Google Scholar: Lookup
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Summary
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The study looked at how matrix type transdermal buprenorphine patches affect horses’ physiological variables and sensitivity to heat pain. The experiment also assessed the patches’ pharmacokinetic profile, which included measuring buprenorphine concentrations in the horses’ blood following application of the patches.
Study Design
- In this randomized experimental study, six adult healthy horses were subjected to three treatments with a 10-day washout period in between. The study used a Latin-square design, a statistical method which eliminates variance when testing two or more variables.
- One group of horses, BUP0, did not receive any treatment and acted as controls. The second group, BUP20, were administered one buprenorphine patch (20 μg h), applied on the base of the tail. This resulted in a dosage of 0.03-0.04 μg kg h. The last group, BUP40, were given two patches (40 μg h), resulting in a dosage of 0.07-0.09 μg kg h.
- To monitor the effects, whole blood samples were taken at specific time intervals for up to 96 hours after the patch was applied. The samples were used to determine buprenorphine concentrations, measure physiological variables, and conduct thermal threshold testing.
Findings
- The study found no significant change to physiological variables such as heart rate, respiratory rate, and body temperature in the horses across different time points.
- When administered the higher dose (40 μg h), there was a noticeable increase in thermal thresholds – reductions in sensitivity to heat pain – in the subjects from 2 to 48 hours. These values were also significantly higher than those observed in the group that received the lower patch dose for multiple time points up to 40 hours.
- The 40 μg h patch led to consistent and measurable plasma concentrations of buprenorphine in the horses’ blood, starting from the 2-hour mark up until 96 hours after application. In fact, mean plasma concentrations of over 0.1 ng/ml were noted from 4 to 40 hours.
Conclusion
- The 20 μg h and 40 μg h doses of the patches were well tolerated by all horses involved in the study.
- With the higher dose, plasma buprenorphine concentrations were consistently measurable and thermal thresholds were effectively blunted for 48 hours as opposed to 32 hours with 20 μg h dosing when compared to the control group.
Cite This Article
APA
Paranjape VV, Knych HK, Berghaus LJ, Cathcart J, Giancola S, Craig H, James C, Saksena S, Reed RA.
(2024).
Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses.
Front Pain Res (Lausanne), 5, 1373555.
https://doi.org/10.3389/fpain.2024.1373555 Publication
Researcher Affiliations
- Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
- K. L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, United States.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
- Department of Civil and Environmental Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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