The pharmacokinetics and pharmacodynamics of fentanyl administered via transdermal patch in horses.
Abstract: Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine. Unassigned: Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at multiple time points following patch placement for the following 96 h. Fentanyl plasma concentration was determined using LC-MS/MS. Data were analyzed using a generalized mixed effects model. Unassigned: Mean (range) maximum plasma concentration (Cmax), time to Cmax, and area under the curve extrapolated to infinity were 1.39 (0.82-1.82), 2.64 (1.21-4.42), 4.11 (2.78-7.12) ng/ml, 12.7 (8.0-16.0), 12.7 (8.0-16.0), 12 (8.0-16.0) h, 42.37 (27.59-55.56), 77.24 (45.62-115.06), 120.34 (100.66-150.55) h ng/ml for LDF, MDF, and HDF, respectively. There was no significant effect of treatment or time on thermal threshold, mechanical threshold, respiratory rate, or temperature ( > 0.063). There was no significant effect of treatment on heart rate ( = 0.364). There was a significant effect of time ( = 0.003) on heart rate with overall heart rates being less than baseline at 64 h. Unassigned: Fentanyl administered via transdermal patch is well absorbed and well tolerated but does not result in an anti-nociceptive effect as measured by thermal and mechanical threshold at the doses studied.
© 2024 Reed, Berghaus, Reynolds, Holmes, Krikorian, Sakai, Ishikawa and Knych.
Publication Date: 2024-03-20 PubMed ID: 38571562PubMed Central: PMC10987731DOI: 10.3389/fpain.2024.1373759Google Scholar: Lookup
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Summary
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The research focuses on understanding how fentanyl, delivered through a transdermal patch system, is absorbed, distributed, metabolized, and expelled in horses. It aims to determine the potential usefulness of this method for pain management in horses.
Study Design
- The research was conducted on six adult horses using a randomized crossover design.
- Treatments were divided into four groups: placebo, low-dose fentanyl (two 100mcg/h patches), medium-dose fentanyl (four 100mcg/h patches), and high-dose fentanyl (six 100mcg/h patches).
- The patches were kept on for 72 hours, following which numerous measurements such as fentanyl plasma concentrations, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained before and after patch placement.
- Fentanyl plasma concentration was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- The data were analyzed using a generalized mixed effects model.
Results
- The researchers found variations in the plasma concentration levels of fentanyl depending on the dosage.
- They did not identify any significant effect of the treatment or time on the thermal threshold, mechanical threshold, respiratory rate, or temperature, suggesting no observed onset of side effects related to these parameters.
- Similarly, there was no significant influence of the treatment on heart rate.
- However, the researchers noticed a significant decrease in heart rate over time, particularly 64 hours after the patches were applied, although the connection to the fentanyl treatment is not explicitly stated.
Conclusion
- Overall, the study concluded that fentanyl delivered through a transdermal patch was well absorbed in horses, and they generally tolerated it well.
- Despite this, researchers found no significant anti-nociceptive (pain-blocking) effect evidenced by the thermal and mechanical thresholds at the administered dosages.
Implications
- This research highlights the need for evaluating the precise dosage of fentanyl that would yield sufficient pain-relief effects when administered via transdermal patches.
- Moreover, the impact of prolonged fentanyl usage on a horse’s heart rate warrants further investigation to ensure the safe use of this pain management technique in veterinary medicine.
Cite This Article
APA
Reed RA, Berghaus LJ, Reynolds RM, Holmes BT, Krikorian AM, Sakai DM, Ishikawa Y, Knych HK.
(2024).
The pharmacokinetics and pharmacodynamics of fentanyl administered via transdermal patch in horses.
Front Pain Res (Lausanne), 5, 1373759.
https://doi.org/10.3389/fpain.2024.1373759 Publication
Researcher Affiliations
- Department of Large Animal Medicine, University of Georgia, Athens, GA, United States.
- Department of Large Animal Medicine, University of Georgia, Athens, GA, United States.
- Department of Large Animal Medicine, University of Georgia, Athens, GA, United States.
- Department of Large Animal Medicine, University of Georgia, Athens, GA, United States.
- Department of Large Animal Medicine, University of Georgia, Athens, GA, United States.
- Department of Small Animal Medicine and Surgery, University of Georgia, Athens, GA, United States.
- Sydney School of Veterinary Science, University of Sydney, Camperdown, NSW, Australia.
- K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California Davis, Davis, CA, United States.
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, 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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