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Frontiers in pain research (Lausanne, Switzerland)2024; 5; 1373555; doi: 10.3389/fpain.2024.1373555

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.
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Publication Date: 2024-03-11 PubMed ID: 38529072PubMed Central: PMC10961409DOI: 10.3389/fpain.2024.1373555Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

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

Frontiers in pain research (Lausanne, Switzerland)
ISSN: 2673-561X
NlmUniqueID: 9918227269806676
Country: Switzerland
Language: English
Volume: 5
Pages: 1373555
PII: 1373555

Researcher Affiliations

Paranjape, Vaidehi V
  • Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
Knych, Heather K
  • K. L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, United States.
Berghaus, Londa J
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
Cathcart, Jessica
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
Giancola, Shyla
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
Craig, Hannah
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
James, Caroline
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
Saksena, Siddharth
  • Department of Civil and Environmental Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
Reed, Rachel A
  • 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.

References

This article includes 49 references
  1. Mama KR, Hector RC. Therapeutic developments in equine pain management.. Vet J (2019) 247:50–6.
    doi: 10.1016/j.tvjl.2019.02.010pubmed: 30971351google scholar: lookup
  2. Sanchez LC, Robertson SA. Pain control in horses: what do we really know?. Equine Vet J (2014) 46(4):517–23.
    doi: 10.1111/evj.12265pubmed: 24645799google scholar: lookup
  3. Nalamachu S, Gudin J. Characteristics of analgesic patch formulations.. J Pain Res (2020) 13:2343–54.
    doi: 10.2147/JPR.S270169pmc: PMC7520099pubmed: 33061549google scholar: lookup
  4. Leppert W, Malec-Milewska M, Zajaczkowska R, Wordliczek J. Transdermal and topical drug administration in the treatment of pain.. Molecules (2018) 23(3):681.
    doi: 10.3390/molecules23030681pmc: PMC6017304pubmed: 29562618google scholar: lookup
  5. Pergolizzi J, Aloisi AM, Dahan A, Filitz J, Langford R, Likar R. Current knowledge of buprenorphine and its unique pharmacological profile.. Pain Pract (2010) 10(5):428–50.
    doi: 10.1111/j.1533-2500.2010.00378.pubmed: 20492579google scholar: lookup
  6. Cowan A, Doxey JC, Harry EJ. The animal pharmacology of buprenorphine, an oripavine analgesic agent.. Br J Pharmacol (1977) 60(4):547–54.
    doi: 10.1111/j.1476-5381.1977.tb07533.xpmc: PMC1667382pubmed: 409449google scholar: lookup
  7. Cowan A. Buprenorphine: new pharmacological aspects.. Int J Clin Pract Suppl (2003) 133:3–24.
    pubmed: 12665117
  8. Galosi M, Troisi A, Toniolo P, Pennasilico L, Cicirelli V, Palumbo Piccionello A. Comparison of the transdermal and intravenous administration of buprenorphine in the management of intra- and postoperative pain in dogs undergoing a unilateral mastectomy.. Animals MDPI (2022) 12(24):3468.
    doi: 10.3390/ani12243468pmc: PMC9774767pubmed: 36552388google scholar: lookup
  9. Andaluz A, Moll X, Ventura R, Abellán R, Fresno L, García F. Plasma buprenorphine concentrations after the application of a 70 microg/h transdermal patch in dogs. Preliminary report.. J Vet Pharmacol Ther (2009) 32(5):503–5.
    doi: 10.1111/j.1365-2885.2009.01058.xpubmed: 19754919google scholar: lookup
  10. Moll X, Fresno L, García F, Prandi D, Andaluz A. Comparison of subcutaneous and transdermal administration of buprenorphine for pre-emptive analgesia in dogs undergoing elective ovariohysterectomy.. Vet J (2011) 187(1):124–8.
    doi: 10.1016/j.tvjl.2009.11.011pubmed: 20056555google scholar: lookup
  11. Pieper K, Schuster T, Levionnois O, Matis U, Bergadano A. Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs.. Vet J (2011) 187(3):335–41.
    doi: 10.1016/j.tvjl.2010.01.013pubmed: 20206560google scholar: lookup
  12. Murrell JC, Robertson SA, Taylor PM, McCown JL, Bloomfield M, Sear JW. Use of a transdermal matrix patch of buprenorphine in cats: preliminary pharmacokinetic and pharmacodynamic data.. Vet Rec (2007) 160(17):578–83.
    doi: 10.1136/vr.160.17.578pubmed: 17468320google scholar: lookup
  13. Thiede AJ, Garcia KD, Stolarik DF, Ma J, Jenkins GJ, Nunamaker EA. Pharmacokinetics of sustained-release and transdermal buprenorphine in göttingen minipigs (Sus scrofa domestica).. J Am Assoc Lab Anim Sci (2014) 53(6):692–9.
    pmc: PMC4253584pubmed: 25650977
  14. Osorio Lujan S, Habre W, Daali Y, Pan Z, Kronen PW. Plasma concentrations of transdermal fentanyl and buprenorphine in pigs (Sus scrofa domesticus).. Vet Anaesth Analg (2017) 44(3):665–75.
    doi: 10.1016/j.vaa.2016.09.002pubmed: 28526486google scholar: lookup
  15. Hakomäki H, Kokki H, Lehtonen M, Räsänen J, Voipio HM, Ranta VP. Maternal and fetal buprenorphine pharmacokinetics in pregnant sheep during transdermal patch dosing: buprenorphine pharmacokinetics in pregnant sheep.. Eur J Pharm Sci (2021) 165:105936.
    doi: 10.1016/j.ejps.2021.105936pubmed: 34273481google scholar: lookup
  16. Hakomäki H, Eskola S, Kokki H, Lehtonen M, Räsänen J, Laaksonen S. Central nervous system distribution of buprenorphine in pregnant sheep, fetuses and newborn lambs after continuous transdermal and single subcutaneous extended-release dosing.. Eur J Pharm Sci (2022) 178:106283.
    doi: 10.1016/j.ejps.2022.106283pubmed: 36029997google scholar: lookup
  17. Smith AA, Halliday LC, Lindeblad MO, Fortman JD. Evaluation of analgesic patches in cynomolgus macaques (Macaca fascicularis).. J Am Assoc Lab Anim Sci (2019) 58(3):356–61.
    doi: 10.30802/AALAS-JAALAS-18-000101pmc: PMC6526491pubmed: 31010456google scholar: lookup
  18. Carregaro AB, Luna SP, Mataqueiro MI, de Queiroz-Neto A. Effects of buprenorphine on nociception and spontaneous locomotor activity in horses.. Am J Vet Res (2007) 68(3):246–50.
    doi: 10.2460/ajvr.68.3.246pubmed: 17331012google scholar: lookup
  19. Schauvliege S. Opioids for field procedures in equine practice.. Vet Rec (2014) 175(24):621–2.
    doi: 10.1136/vr.g7571pubmed: 25523998google scholar: lookup
  20. Taylor PM, Hoare HR, de Vries A, Love EJ, Coumbe KM, White KL. A multicentre, prospective, randomised, blinded clinical trial to compare some perioperative effects of buprenorphine or butorphanol premedication before equine elective general anaesthesia and surgery.. Equine Vet J (2016) 48(4):442–50.
    doi: 10.1111/evj.12442pmc: PMC5033022pubmed: 25772950google scholar: lookup
  21. Love EJ, Pelligand L, Taylor PM, Murrell JC, Sear JW. Pharmacokinetic-pharmacodynamic modelling of intravenous buprenorphine in conscious horses.. Vet Anaesth Analg (2015) 42(1):17–29.
    doi: 10.1111/vaa.12165pubmed: 24735059google scholar: lookup
  22. Flynn H, Cenani A, Brosnan RJ, DiMaio Knych HK, de Araujo Aguiar AJ. Pharmacokinetics and pharmacodynamics of a high concentration of buprenorphine (simbadol) in conscious horses after subcutaneous administration.. Vet Anaesth Analg (2021) 48(4):585–95.
    doi: 10.1016/j.vaa.2021.02.005pubmed: 33934992google scholar: lookup
  23. Risberg ÅI, Spadavecchia C, Ranheim B, Hendrickson EH, Lervik A, Haga HA. Antinociceptive effect of buprenorphine and evaluation of the nociceptive withdrawal reflex in foals.. Vet Anaesth Analg (2015) 42(3):329–38.
    doi: 10.1111/vaa.12205pubmed: 25041444google scholar: lookup
  24. Love EJ, Taylor PM, Murrell J, Whay HR. Effects of acepromazine, butorphanol and buprenorphine on thermal and mechanical nociceptive thresholds in horses.. Equine Vet J (2012) 44(2):221–5.
    doi: 10.1111/j.2042-3306.2011.00412.xpubmed: 21696438google scholar: lookup
  25. Taylor P. Remote controlled nociceptive threshold testing systems in large animals.. Animals MDPI (2020) 10(9):1556.
    doi: 10.3390/ani10091556pmc: PMC7552262pubmed: 32887292google scholar: lookup
  26. Poller C, Hopster K, Rohn K, Kästner SB. Nociceptive thermal threshold testing in horses—effect of neuroleptic sedation and neuroleptanalgesia at different stimulation sites.. BMC Vet Res (2013) 9:135.
    doi: 10.1186/1746-6148-9-135pmc: PMC3708779pubmed: 23837730google scholar: lookup
  27. Poller C, Hopster K, Rohn K, Kästner SB. Evaluation of contact heat thermal threshold testing for standardized assessment of cutaneous nociception in horses—comparison of different locations and environmental conditions.. BMC Vet Res (2013) 9:4.
    doi: 10.1186/1746-6148-9-4pmc: PMC3551666pubmed: 23298405google scholar: lookup
  28. Park I, Kim D, Song J, In CH, Jeong SW, Lee SH. Buprederm, a new transdermal delivery system of buprenorphine: pharmacokinetic, efficacy and skin irritancy studies.. Pharm Res (2008) 25:1052–62.
    doi: 10.1007/s11095-007-9470-6pubmed: 18236140google scholar: lookup
  29. Evans HC, Easthope SE. Transdermal buprenorphine.. Drugs (2003) 63:1999–2010; discussion 2011–2.
    doi: 10.2165/00003495-200363190-00003pubmed: 12962515google scholar: lookup
  30. Sittl R, Griessinger N, Likar R. Analgesic efficacy and tolerability of transdermal buprenorphine in patients with inadequately controlled chronic pain related to cancer and other disorders: a multicenter, randomized, double-blind, placebo-controlled trial.. Clin Ther (2003) 25:150–68.
    doi: 10.1016/s0149-2918(03)90019-1pubmed: 12637117google scholar: lookup
  31. Ko JC, Freeman LJ, Barletta M, Weil AB, Payton ME, Johnson BM. Efficacy of oral transmucosal and intravenous administration of buprenorphine before surgery for postoperative analgesia in dogs undergoing ovariohysterectomy.. J Am Vet Med Assoc (2011) 238:318–28.
    doi: 10.2460/javma.238.3.318pubmed: 21281215google scholar: lookup
  32. Nunamaker EA, Stolarik DF, Ma J, Wilsey AS, Jenkins GJ, Medina CL. Clinical efficacy of sustained-release buprenorphine with meloxicam for postoperative analgesia in beagle dogs undergoing ovariohysterectomy.. J Am Assoc Lab Anim Sci (2014) 53:494–501.
    pmc: PMC4181691pubmed: 25255072
  33. Carregaro AB, Neto FJ, Beier SL, Luna SP. Cardiopulmonary effects of buprenorphine in horses.. Am J Vet Res (2006) 67:1675–80.
    doi: 10.2460/ajvr.67.10.1675pubmed: 17014315google scholar: lookup
  34. Emanuel D, Kästner SBR, Delarocque J, Grob AJ, Bienert-Zeit A. Influence of butorphanol, buprenorphine and levomethadone on sedation quality and postoperative analgesia in horses undergoing cheek tooth extraction.. Vet Sci (2022) 9:174.
    doi: 10.3390/vetsci9040174pmc: PMC9029614pubmed: 35448672google scholar: lookup
  35. Cruz FS, Carregaro AB, Machado M, Antonow RR. Sedative and cardiopulmonary effects of buprenorphine and xylazine in horses.. Can J Vet Res (2011) 75:35–41.
    pmc: PMC3003560pubmed: 21461193
  36. Potter JJ, MacFarlane PD, Love EJ, Tremaine H, Taylor PM, Murrell JC. Preliminary investigation comparing a detomidine continuous rate infusion combined with either morphine or buprenorphine for standing sedation in horses.. Vet Anaesth Analg (2016) 43:189–94.
    doi: 10.1111/vaa.12316pubmed: 26479277google scholar: lookup
  37. Taylor P, Coumbe K, Henson F, Scott D, Taylor A. Evaluation of sedation for standing clinical procedures in horses using detomidine combined with buprenorphine.. Vet Anaesth Analg (2014) 41:14–24.
    doi: 10.1111/vaa.12055pubmed: 23742694google scholar: lookup
  38. Davis JL, Messenger KM, LaFevers DH, Barlow BM, Posner LP. Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse.. J Vet Pharmacol Ther (2012) 35:52–8.
    doi: 10.1111/j.1365-2885.2011.01284.xpubmed: 21392040google scholar: lookup
  39. Love EJ, Taylor PM, Murrell J, Whay HR, Waterman-Pearson AE. Assessment of the sedative effects of buprenorphine administered with 10 μg/kg detomidine in horses.. Vet Rec (2011) 168:379.
    doi: 10.1136/vr.c7288pubmed: 21498267google scholar: lookup
  40. Grubb TL, Kurkowski D, Sellon DC, Seino KK, Coffey T, Davis JL. Pharmacokinetics and physiologic/behavioral effects of buprenorphine administered sublingually and intravenously to neonatal foals.. J Vet Pharmacol Ther (2019) 42:26–36.
    doi: 10.1111/jvp.12715pubmed: 30242851google scholar: lookup
  41. Rigotti C, De Vries A, Taylor PM. Buprenorphine provides better anaesthetic conditions than butorphanol for field castration in ponies: results of a randomised clinical trial.. Vet Rec (2014) 175:623.
    doi: 10.1136/vr.102729pubmed: 25262056google scholar: lookup
  42. Messenger KM, Davis JL, LaFevers DH, Barlow BM, Posner LP. Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site.. Vet Anaesth Analg (2011) 38:374–84.
    doi: 10.1111/j.1467-2995.2011.00613.xpubmed: 21501371google scholar: lookup
  43. Walker AF. Sublingual administration of buprenorphine for long-term analgesia in the horse.. Vet Rec (2007) 160:808–9.
    doi: 10.1136/vr.160.23.808pubmed: 17558032google scholar: lookup
  44. Levionnois OL, Graubner C, Spadavecchia C. Colon constipation in horses after sustained-release buprenorphine administration.. Vet Anaesth Analg (2018) 45:876–80.
    doi: 10.1016/j.vaa.2018.08.004pubmed: 30297131google scholar: lookup
  45. Brown SM, Holtzman M, Kim T, Kharasch ED. Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active.. Anesthesiology (2011) 115:1251–60.
    doi: 10.1097/ALN.0b013e318238fea0pmc: PMC3560935pubmed: 22037640google scholar: lookup
  46. Bird D, Ravindra NM. Transdermal drug delivery and patches—an overview.. Med Devices Sens (2020) 3:e10069.
    doi: 10.1002/mds3.10069google scholar: lookup
  47. Al Hanbali OA, Khan HMS, Sarfraz M, Arafat M, Ijaz S, Hameed A. Transdermal patches: design and current approaches to painless drug delivery.. Acta Pharm (2019) 69:197–215.
    doi: 10.2478/acph-2019-0016pubmed: 31259729google scholar: lookup
  48. Mills PC, Cross SE. Regional differences in transdermal penetration of fentanyl through equine skin.. Res Vet Sci (2007) 82:252–6.
    doi: 10.1016/j.rvsc.2006.07.015pubmed: 17011603google scholar: lookup
  49. Skrzypczak H, Reed R, Brainard B, Sakai D, Barletta M, Quandt J. The pharmacokinetics of a fentanyl matrix patch applied at three different anatomical locations in horses.. Equine Vet J (2022) 54:153–8.
    doi: 10.1111/evj.13424pubmed: 33453066google scholar: lookup

Citations

This article has been cited 1 times.
  1. Paranjape VV, Knych HK, Berghaus LJ, Giancola S, Cathcart J, Reed RA. Plasma concentrations of buprenorphine administered via matrix-type transdermal patches applied at three different anatomical locations in healthy adult horses. Front Pain Res (Lausanne) 2024;5:1390322.
    doi: 10.3389/fpain.2024.1390322pubmed: 38962712google scholar: lookup
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