FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Frontiers in pain research (Lausanne, Switzerland)2024; 5; 1390322; doi: 10.3389/fpain.2024.1390322

Plasma concentrations of buprenorphine administered via matrix-type transdermal patches applied at three different anatomical locations in healthy adult horses.

Abstract: Anatomical location-dependent differences in transdermal opioid penetration are well described in human patients. Although this has been investigated in horses with fentanyl, there is no literature available on location-dependent plasma buprenorphine concentrations when administered as a transdermal matrix-type patch. Unassigned: This study aims to compare the plasma concentrations achieved from the matrix-type transdermal buprenorphine patches placed at different anatomical sites (metacarpus, gaskin, and ventral tail base) in healthy adult horses. Unassigned: This is a randomized experimental study with a Latin square design. Unassigned: Six adult horses were given each of three treatments with a minimum 10-day washout period. For each treatment, two 20 μg h matrix-type buprenorphine patches were applied to the ventral aspect of the tail base (Tail), metacarpus region (Metacarpus), or gaskin region (Gaskin). Whole blood samples (for determination of buprenorphine concentration) and physiological variables were collected before (0 h) and at 0.5, 2, 4, 6, 8, 10, 12, 16, 24, 32, 48, 56, 72, 96 and 120 h after patches were applied. The patches were removed 96 h following placement and were analyzed for residual buprenorphine content. Buprenorphine concentrations were measured in plasma by LC-MS/MS. A mixed-effects model was used to analyze the physiological variables. Unassigned: Between the three treatment groups, there was no change in physiological variables across timepoints as compared to baseline and when compared to each other in a single horse and between horses ( > 0.3). When comparing all three locations, the buprenorphine uptake was observed to be more consistent with respect to measurable plasma concentrations >0.1 ng ml when applied to the ventral aspect of the tail base. In the Tail group, the mean plasma buprenorphine concentrations were >0.1 ng ml from 2 to 32 h. The highest group mean was 0.25 ng ml noted at 4 h. Unassigned: The metacarpal and gaskin regions presented more erratic and inconsistent buprenorphine uptake and plasma concentrations as compared to the ventral aspect of the tail base. Further research must be directed at investigating the optimal dose, achievable duration of analgesia, change in measurable plasma concentrations, and behavioral and systemic effects.
© 2024 Paranjape, Knych, Berghaus, Giancola, Cathcart and Reed.
Get Full Text
Publication Date: 2024-06-19 PubMed ID: 38962712PubMed Central: PMC11220193DOI: 10.3389/fpain.2024.1390322Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

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.

This study explored how the transdermal application of buprenorphine patches on different anatomical areas of a horse affects the drug’s concentration in the bloodstream. The results indicate that amongst three tested areas, the ventral base of the tail offered the most consistent drug uptake.

Research Aim

  • The goal of this study was to compare plasma concentrations of buprenorphine, an opioid used for pain management, when administered via transdermal patches applied to different locations on a horse’s body, namely the tail base, metacarpus (lower leg), and gaskin (the area of the hind leg between the stifle and hock).

Methodology

  • This was a randomized trial, with six adult horses undergoing three different treatments, each followed by a 10-day washout period to ensure no carryover effects.
  • For each treatment, two buprenorphine patches were applied to the horse’s tail, lower leg, or gaskin.
  • Blood samples were collected at varying intervals after the patches were applied, up to a total of 120 hours. Heart rate, respiratory rate, and body temperature were some of the physiological parameters that were monitored.
  • The patches were then removed 96 hours post-application and tested for remaining buprenorphine content. A mixed-effects model was used to analyze the relationship between physiological variables and buprenorphine concentration in the bloodstream.

Findings

  • The study found no significant change in physiological variables over time or between different horses when comparing the three treatment groups.
  • Transdermal patches applied at the ventral base of the tail were found to be the most consistent in terms of measurable plasma buprenorphine concentrations.
  • In the group where patches were applied to the tail base, the mean plasma buprenorphine concentrations were >0.1 ng/mL from 2 to 32 hours.
  • The metacarpal and gaskin regions showed more erratic and inconsistent drug uptake and plasma concentrations as compared to the tail base.

Conclusion

  • This research provides valuable insights into how placement affects the uptake of matrix-type transdermal buprenorphine patches in horses. However, further research is needed to ascertain the optimal dose, determine the duration of the drug’s analgesic effect, assess changes in measurable plasma concentrations, and understand related behavioral and systemic effects.

Cite This Article

APA
Paranjape VV, Knych HK, Berghaus LJ, Giancola S, Cathcart J, Reed RA. (2024). Plasma concentrations of buprenorphine administered via matrix-type transdermal patches applied at three different anatomical locations in healthy adult horses. Front Pain Res (Lausanne), 5, 1390322. https://doi.org/10.3389/fpain.2024.1390322

Publication

Frontiers in pain research (Lausanne, Switzerland)
ISSN: 2673-561X
NlmUniqueID: 9918227269806676
Country: Switzerland
Language: English
Volume: 5
Pages: 1390322
PII: 1390322

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.
Giancola, Shyla
  • 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.
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 authors 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 51 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, et al. Current knowledge of buprenorphine and its unique pharmacological profile. Pain Pract (2010) 10(5):428–50.
    doi: 10.1111/j.1533-2500.2010.00378.xpubmed: 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, et al. 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. Lujan SO, 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, et al. 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, et al. 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, et al. 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. Paranjape V, Berghaus L, Cathcart J, Giancola S, Craig H, James C, Saksena S, Reed R. Evaluation of physical examination and thermal nociceptive threshold testing during placement of transdermal buprenorphine patch in healthy adult horses. Vet Anaesth Analg (2023) 50(1): E115.
    doi: 10.1016/j.vaa.2022.09.022pmc: PMC10961409pubmed: 38529072google scholar: lookup
  26. Paranjape VV, Knych HK, Berghaus LJ, Cathcart J, Giancola S, Craig H, et al. 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) (2024) 11:1373555.
    doi: 10.3389/fpain.2024.1373555pmc: PMC10961409pubmed: 38529072google scholar: lookup
  27. Skrzypczak H, Reed R, Brainard B, Sakai D, Barletta M, Quandt J, et al. 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
  28. Buchholz T, Hildebrand M, Heider A, Stenger V, Arens D, Spadavecchia C, et al. Transdermal fentanyl uptake at two different patch locations in Swiss white alpine sheep. Animals (Basel) (2020) 10(9):1675.
    doi: 10.3390/ani10091675pmc: PMC7552603pubmed: 32957484google scholar: lookup
  29. Mirschberger V, von Deimling C, Heider A, Spadavecchia C, Rohrbach H, Zeiter S. Fentanyl plasma concentrations after application of a transdermal patch in three different locations to refine postoperative pain management in rabbits. Animals MDPI (2020) 10(10):1778.
    doi: 10.3390/ani10101778pmc: PMC7601434pubmed: 33019557google scholar: lookup
  30. Bormann JL, Maibach HI. Effects of anatomical location on in vivo percutaneous penetration in man. Cutan Ocul Toxicol (2020) 39(3):213–22.
    doi: 10.1080/15569527.2020.1787434pubmed: 32643443google scholar: lookup
  31. Riviere JE, Papich MG. Potential and problems of developing transdermal patches for veterinary applications. Adv Drug Deliv Rev (2001) 50(3):175–203.
    doi: 10.1016/s0169-409x(01)00157-0pubmed: 11500227google scholar: lookup
  32. Mills PC, Cross SE. Regional differences in transdermal penetration of fentanyl through equine skin. Res Vet Sci (2007) 82(2):252–6.
    doi: 10.1016/j.rvsc.2006.07.015pubmed: 17011603google scholar: lookup
  33. Thomasy SM, Slovis N, Maxwell LK, Kollias-Baker C. Transdermal fentanyl combined with nonsteroidal anti-inflammatory drugs for analgesia in horses. J Vet Intern Med (2004) 18(4):550–4.
    doi: 10.1892/0891-6640(2004)18<550:tfcwna>2.0.co;2pubmed: 15320597google scholar: lookup
  34. Maxwell LK, Thomasy SM, Slovis N, Kollias-Baker C. Pharmacokinetics of fentanyl following intravenous and transdermal administration in horses. Equine Vet J (2003) 35(5):484–90.
    doi: 10.2746/042516403775600415pubmed: 12875327google scholar: lookup
  35. Orsini JA, Moate PJ, Kuersten K, Soma LR, Boston RC. Pharmacokinetics of fentanyl delivered transdermally in healthy adult horses–variability among horses and its clinical implications. J Vet Pharmacol Ther (2006) 29(6):539–46.
    doi: 10.1111/j.1365-2885.2006.00796.xpubmed: 17083458google scholar: lookup
  36. Ortega McCormack JJ, Reed RA, Epstein KL, Camus MS, Knych HK. Longitudinal evaluation of fentanyl concentrations in equine plasma and synovial fluid following application of transdermal fentanyl patches over one carpal joint. Vet Surg (2023) 52(8):1150–7.
    doi: 10.1111/vsu.13990pubmed: 37537748google scholar: lookup
  37. Bird D, Ravindra NM. Transdermal drug delivery and patches—an overview. Med Devices Sens (2020) 3:e10069.
    doi: 10.1002/mds3.10069google scholar: lookup
  38. 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
  39. 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
  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. 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
  42. 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
  43. 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
  44. 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
  45. 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
  46. 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
  47. 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
  48. 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
  49. 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
  50. 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
  51. 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

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,850 horse owners like you who receive our email updates on horse health and nutrition.