Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses

BackgroundMatrix 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.ObjectiveAssessment of the physiological variables (heart rate, respiratory...

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Main Authors: Vaidehi V. Paranjape, Heather K. Knych, Londa J. Berghaus, Jessica Cathcart, Shyla Giancola, Hannah Craig, Caroline James, Siddharth Saksena, Rachel A. Reed
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Pain Research
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpain.2024.1373555/full
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author Vaidehi V. Paranjape
Heather K. Knych
Londa J. Berghaus
Jessica Cathcart
Shyla Giancola
Hannah Craig
Caroline James
Siddharth Saksena
Rachel A. Reed
author_facet Vaidehi V. Paranjape
Heather K. Knych
Londa J. Berghaus
Jessica Cathcart
Shyla Giancola
Hannah Craig
Caroline James
Siddharth Saksena
Rachel A. Reed
author_sort Vaidehi V. Paranjape
collection DOAJ
description BackgroundMatrix 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.ObjectiveAssessment 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−1 and 40 μg h−1 dosing) in healthy adult horses.Study designRandomised experimental study with a Latin-square design.MethodsSix 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−1) applied on the ventral aspect of the tail base resulting in a dose of 0.03–0.04 μg kg−1 h−1. BUP40 horses received two patches placed alongside each other (40 μg h−1) on the tail base resulting in a dose of 0.07–0.09 μg kg−1 h−1. 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.ResultsBetween the three groups, there was no change in physiological variables across timepoints as compared to baseline (p > 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−1 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.Conclusions20 μg h−1 and 40 μg h−1 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−1 dosing as compared to control.
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spelling doaj.art-5ee3b3aaf76f412595c36b475098b3a82024-03-11T04:36:01ZengFrontiers Media S.A.Frontiers in Pain Research2673-561X2024-03-01510.3389/fpain.2024.13735551373555Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horsesVaidehi V. Paranjape0Heather K. Knych1Londa J. Berghaus2Jessica Cathcart3Shyla Giancola4Hannah Craig5Caroline James6Siddharth Saksena7Rachel A. Reed8Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesK. L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, United StatesDepartment of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United StatesDepartment of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United StatesDepartment of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United StatesDepartment of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United StatesDepartment of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United StatesDepartment of Civil and Environmental Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesDepartment of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United StatesBackgroundMatrix 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.ObjectiveAssessment 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−1 and 40 μg h−1 dosing) in healthy adult horses.Study designRandomised experimental study with a Latin-square design.MethodsSix 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−1) applied on the ventral aspect of the tail base resulting in a dose of 0.03–0.04 μg kg−1 h−1. BUP40 horses received two patches placed alongside each other (40 μg h−1) on the tail base resulting in a dose of 0.07–0.09 μg kg−1 h−1. 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.ResultsBetween the three groups, there was no change in physiological variables across timepoints as compared to baseline (p > 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−1 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.Conclusions20 μg h−1 and 40 μg h−1 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−1 dosing as compared to control.https://www.frontiersin.org/articles/10.3389/fpain.2024.1373555/fullopioidsequineanalgesiapainpharmacologythermal antinociception
spellingShingle Vaidehi V. Paranjape
Heather K. Knych
Londa J. Berghaus
Jessica Cathcart
Shyla Giancola
Hannah Craig
Caroline James
Siddharth Saksena
Rachel A. Reed
Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses
Frontiers in Pain Research
opioids
equine
analgesia
pain
pharmacology
thermal antinociception
title Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses
title_full Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses
title_fullStr Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses
title_full_unstemmed Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses
title_short Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses
title_sort evaluation of physical variables thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix type patch in healthy adult horses
topic opioids
equine
analgesia
pain
pharmacology
thermal antinociception
url https://www.frontiersin.org/articles/10.3389/fpain.2024.1373555/full
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