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Journal of veterinary pharmacology and therapeutics2020; 44(3); 349-358; doi: 10.1111/jvp.12939

Bayesian-based withdrawal estimates using pharmacokinetic parameters for two capsaicinoid-containing products administered to horses.

Abstract: Capsaicinoids deter horses from chewing on bandages and are applied topically to provide analgesia to musculoskeletal injuries. They are banned during competition due to their nerve blocking properties. The pharmacokinetics of oral (PO) and direct gastric administration via nasogastric tube (NG), or topical (TOP) administration of two capsaicinoid-containing products were investigated, and the withdrawal times required prior to competition were estimated. Capsaicin (CAP) and dihydrocapsaicin (DCAP) were quantified in plasma, and both compounds were best described by a delayed absorption two compartment elimination model following PO administration and by a first order absorption one compartment elimination model following TOP administration. Capsaicin and DCAP could not be quantified in most samples following NG administration. Following PO administration, the time to maximum plasma concentration (T ) for CAP and DCAP was 0.25 (0.08-0.50) hr. Following TOP application, the Tmax for CAP and DCAP was 4 (2-6) and 5 (3-12) hr, respectively. By 8 hr post-PO administration and 36 hr post-TOP application, CAP and DCAP were below the lower limit of quantification. Capsaicin and DCAP were not detected in urine samples. Withdrawal times were predicted using the 99.99% credibility interval limits of the pharmacokinetic parameters calculated with Bayesian estimation.
© 2020 John Wiley & Sons Ltd.
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Publication Date: 2020-12-11 PubMed ID: 33305843DOI: 10.1111/jvp.12939Google 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.

This research study explores the pharmacokinetics of capsaicinoids, compounds used topically on horses to prevent them from chewing bandages and provide analgesia for musculoskeletal injuries. The study aims to determine the withdrawal times required for capsaicinoids prior to competition through oral and topical administration methods.

Research Methods and Findings

  • The study involved investigating the pharmacokinetics of two capsaicinoid-containing products through oral (PO), direct gastric administration via a nasogastric tube (NG), and topical (TOP) applications.
  • The researchers quantified capsaicin (CAP) and dihydrocapsaicin (DCAP) in the plasma of horses following administration. Various model analyses were conducted to describe the compounds’ absorption and elimination patterns. After PO administration, CAP and DCAP were best described by a delayed absorption two compartment elimination model. On the other hand, these compounds followed a first-order absorption one-compartment elimination model after TOP application.
  • The study found that the time to maximum plasma concentration (Tmax) for both CAP and DCAP was fastest following oral administration (0.25 hr). This outcome is slower with topical administration, taking 4 hr for CAP and 5 hr for DCAP.
  • Eight hours after oral administration and 36 hours after topical application, the capsaicinoid levels in the plasma went below the lower limit of quantification, meaning the levels became too low to be accurately measured. Importantly, these compounds were undetectable in urine samples.
  • Finally, the team estimated the withdrawal times – the duration before a competition when capsaicinoid use should be ceased – using the 99.99% credibility interval limits of the pharmacokinetic parameters calculated with Bayesian estimation. The specifics of these withdrawal times, however, were not detailed in the abstract.

Significance of the Research

  • This research provides essential pharmacokinetic data on the use of capsaicinoids in horses, including absorption, distribution, and elimination patterns. The data can assist veterinarians and horse trainers to safely and effectively use capsaicinoids and comply with competition regulations – making sure that capsaicinoid levels are negligible or absent from the horse’s system before a race.
  • The study also demonstrates the value of using advanced statistical methods, such as Bayesian estimation, in predicting pharmacokinetic parameters and prescribing effective withdrawal times.

Cite This Article

APA
Robinson MA, Stefanovski D, You Y, Boston RC, Soma LR. (2020). Bayesian-based withdrawal estimates using pharmacokinetic parameters for two capsaicinoid-containing products administered to horses. J Vet Pharmacol Ther, 44(3), 349-358. https://doi.org/10.1111/jvp.12939

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 44
Issue: 3
Pages: 349-358

Researcher Affiliations

Robinson, Mary A
  • Department of Clinical Studies - New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, PA, USA.
  • Pennsylvania Equine Toxicology & Research Laboratory, West Chester, PA, USA.
Stefanovski, Darko
  • Department of Clinical Studies - New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, PA, USA.
You, Youwen
  • Department of Clinical Studies - New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, PA, USA.
  • Pennsylvania Equine Toxicology & Research Laboratory, West Chester, PA, USA.
Boston, Raymond C
  • Department of Clinical Studies - New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, PA, USA.
Soma, Lawrence R
  • Department of Clinical Studies - New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, PA, USA.

MeSH Terms

  • Administration, Oral
  • Administration, Topical
  • Animals
  • Bayes Theorem
  • Horses

Grant Funding

  • 4400016165 / Pennsylvania Department of Agriculture State Horse Racing Commission
  • Pennsylvania Harness Horsemen's Association
  • Meadows Standardbred Owners Association
  • Pennsylvania Horsemen's Benevolent and Protective Association
  • Pennsylvania Thoroughbred Horsemen's Association

References

This article includes 36 references
  1. Bode AM, Dong Z. The two faces of capsaicin. Cancer Research 71(8), 2809-2814.
    doi: 10.1158/0008-5472.can-10-3756google scholar: lookup
  2. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature 389(6653), 816-824.
    doi: 10.1038/39807google scholar: lookup
  3. Chrubasik S, Weiser T, Beime B. Effectiveness and safety of topical capsaicin cream in the treatment of chronic soft tissue pain. Phytotherapy Research 24(12), 1877-1885.
    doi: 10.1002/ptr.3335google scholar: lookup
  4. Conway SJ. TRPing the switch on pain: An introduction to the chemistry and biology of capsaicin and TRPV1. Chemical Society Reviews 37(8), 1530-1545.
    doi: 10.1039/b610226ngoogle scholar: lookup
  5. Cordell GA, Araujo OE. Capsaicin: Identification, nomenclature, and pharmacotherapy. Annals of Pharmacotherapy 27(3), 330-336.
    doi: 10.1177/106002809302700316google scholar: lookup
  6. Csizmadia F, Tsantili-Kakoulidou A, Panderi I, Darvas F. Prediction of distribution coefficient from structure. 1. Estimation method. Journal of Pharmaceutical Sciences 86(7), 865-871.
    doi: 10.1021/js960177kgoogle scholar: lookup
  7. Donnerer J, Amann R, Schuligoi R, Lembeck F. Absorption and metabolism of capsaicinoids following intragastric administration in rats. Naunyn-Schmiedebergs Archives of Pharmacology 342(3), 357-361.
    doi: 10.1007/bf00169449google scholar: lookup
  8. Gabrielsson JL, Weiner DL. Pharmacokinetic & Pharmacodynamic Data Analysis: Concepts and Applications, 4th ed. Swedish Pharmaceutical Press .
  9. Govindarajan VS, Salzer UJ. Capsicum production, technology, chemistry, and quality. Part 1: History, botany, cultivation, and primary processing. Critical Reviews in Food Science & Nutrition 22(2), 109-176.
    doi: 10.1080/10408398509527412google scholar: lookup
  10. Holzer P. Capsaicin: Cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacological Reviews 43(2), 143-201.
  11. Jancso N, Jancso-Gabor A, Szolcsanyi J. Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. British Journal of Pharmacology and Chemotherapy 31(1), 138-151.
    doi: 10.1111/j.1476-5381.1967.tb01984.xgoogle scholar: lookup
  12. Jones VM, Moore KA, Peterson DM. Capsaicin 8% topical patch (Qutenza)-a review of the evidence. Journal of Pain & Palliative Care Pharmacotherapy 25(1), 32-41.
    doi: 10.3109/15360288.2010.547561google scholar: lookup
  13. Kawada T, Iwai K. In vivo and in vitro metabolism of dihydrocapsaicin. Agricultural and Biological Chemistry 49(2), 441-448.
    doi: 10.1080/00021369.1985.10866743google scholar: lookup
  14. Kawada T, Suzuki T, Takahashi M, Iwai K. Gastrointestinal absorption and metabolism of capsaicin and dihydrocapsaicin in rats. Toxicology & Applied Pharmacology 72(3), 449-456.
    doi: 10.1016/0041-008x(84)90121-2google scholar: lookup
  15. Kennedy WR, Vanhove GF, Lu S-P, Tobias J, Bley KR, Walk D, Wendelschafer-Crabb G, Simone DA, Selim MM. A randomized, controlled, open-label study of the long-term effects of NGX-4010, a high-concentration capsaicin patch, on epidermal nerve fiber density and sensory function in healthy volunteers. Journal of Pain 11(6), 579-587.
    doi: 10.1016/j.jpain.2009.09.019google scholar: lookup
  16. Klopman G, Li JY, Wang S, Dimayuga MJ. Computer automated log P calculations based on an extended group contribution approach. Journal of Chemical Information and Computer Sciences 34(4), 752-781.
    doi: 10.1021/ci00020a009google scholar: lookup
  17. Kosuwon W, Sirichatiwapee W, Wisanuyotin T, Jeeravipoolvarn P, Laupattarakasem W. Efficacy of symptomatic control of knee osteoarthritis with 0.0125% of capsaicin versus placebo. Journal of the Medical Association of Thailand 93(10), 1188-1195.
  18. Malmberg AB, Mizisin AP, Calcutt NA, von Stein T, Robbins WR, Bley KR. Reduced heat sensitivity and epidermal nerve fiber immunostaining following single applications of a high-concentration capsaicin patch. Pain 111(3), 360-367.
    doi: 10.1016/j.pain.2004.07.017google scholar: lookup
  19. McCormack PL. Capsaicin dermal patch: In non-diabetic peripheral neuropathic pain. Drugs 70(14), 1831-1842.
    doi: 10.2165/11206050-000000000-00000google scholar: lookup
  20. Pedersen SF, Owsianik G, Nilius B. TRP channels: An overview. Cell Calcium 38(3-4), 233-252.
    doi: 10.1016/j.ceca.2005.06.028google scholar: lookup
  21. Reilly CA, Crouc DJ, Yost GS, Fatah AA. Determination of capsaicin, dihydrocapsaicin, and nonivamide in self-defense weapons by liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. Journal of Chromatography. A 912(2), 259-267.
    doi: 10.1016/s0021-9673(01)00574-xgoogle scholar: lookup
  22. Reilly CA, Yost GS. Metabolism of capsaicinoids by P450 enzymes: A review of recent findings on reaction mechanisms, bio-activation, and detoxification processes. Drug Metabolism Reviews 38(4), 685-706.
    doi: 10.1080/03602530600959557google scholar: lookup
  23. Riviere JE, Papich MG, Adams HR. Dermopharmacology: drugs acting on the skin. Veterinary Pharmacology & Therapeutics pp. 1281-1283, 9th ed.
  24. RMTC. Explaining the 95/95 Tolerance Interval. .
  25. Robbins WR, Staats PS, Levine J, Fields HL, Allen RW, Campbell JN, Pappagallo M. Treatment of intractable pain with topical large-dose capsaicin: Preliminary report. Anesthesia & Analgesia 86(3), 579-583.
    doi: 10.1097/00000539-199803000-00027google scholar: lookup
  26. Roberts GO, Rosenthal JS. Optimal scaling for various Metropolis-Hastings algorithms. Statistical Science 16, 351-367.
    doi: 10.1214/ss/1015346320google scholar: lookup
  27. Roberts K, Shenoy R, Anand P. A novel human volunteer pain model using contact heat evoked potentials (CHEP) following topical skin application of transient receptor potential agonists capsaicin, menthol and cinnamaldehyde. Journal of Clinical Neuroscience 18(7), 926-932.
    doi: 10.1016/j.jocn.2010.11.015google scholar: lookup
  28. Seino KK, Foreman JH, Greene SA, Goetz TE, Benson GJ. Effects of topical perineural capsaicin in a reversible model of equine foot lameness. Journal of Veterinary Internal Medicine 17(4), 563-566.
    doi: 10.1111/j.1939-1676.2003.tb02479.xgoogle scholar: lookup
  29. Simpson DM, Gazda S, Brown S, Webster LR, Lu S-P, Tobias JK, Vanhove GF. Long-term safety of NGX-4010, a high-concentration capsaicin patch, in patients with peripheral neuropathic pain. Journal of Pain & Symptom Management 39(6), 1053-1064.
    doi: 10.1016/j.jpainsymman.2009.11.316google scholar: lookup
  30. Suresh D, Srinivasan K. Tissue distribution & elimination of capsaicin, piperine & curcumin following oral intake in rats. Indian Journal of Medical Research 131, 682-691.
  31. Szallasi A, Appendino G. Vanilloid receptor TRPV1 antagonists as the next generation of painkillers. Are we putting the cart before the horse?. Journal of Medicinal Chemistry 47(11), 2717-2723.
    doi: 10.1021/jm030560jgoogle scholar: lookup
  32. Toutain PL. How to extrapolate a withdrawal time from an EHSLC published detection time: A Monte Carlo simulation appraisal. Equine Veterinary Journal 42(3), 248-254.
    doi: 10.1111/j.2042-3306.2010.00028.xgoogle scholar: lookup
  33. Viswanadhan VN, Ghose AK, Revankar GR, Robins RK. Atomic physicochemical parameters for three dimensional structure directed quantitative structure-activity relationships. 4. Additional parameters for hydrophobic and dispersive interactions and their application for an automated superposition of certain naturally occurring nucleoside antibiotics. Journal of Chemical Information and Computer Sciences 29(3), 163-172.
    doi: 10.1021/ci00063a006google scholar: lookup
  34. Yaksh TL, Farb DH, Leeman SE, Jessell TM. Intrathecal capsaicin depletes substance P in the rat spinal cord and produces prolonged thermal analgesia. Science 206(4417), 481-483.
    doi: 10.1126/science.228392google scholar: lookup
  35. You Y, Uboh CE, Soma LR, Guan F, Taylor D, Li X, Liu Y, Chen J. Validated UHPLC-MS-MS method for rapid analysis of capsaicin and dihydrocapsaicin in equine plasma for doping control. Journal of Analytical Toxicology 37(2), 122-132.
    doi: 10.1093/jat/bks098google scholar: lookup
  36. Zak A, Siwinska N, Slowikowska M, Borowicz H, Szpot P, Zawadzki M, Niedzwiedz A. The detection of capsaicin and dihydrocapsaicin in horse serum following long-term local administration. BMC Veterinary Research 14(1), 193.
    doi: 10.1186/s12917-018-1518-9google scholar: lookup

Citations

This article has been cited 1 times.
  1. de Tonnerre DJ, Medina Torres CE, Stefanovski D, Robinson MA, Kemp KL, Bertin FR, van Eps AW. Effect of sirolimus on insulin dynamics in horses. J Vet Intern Med 2023 Mar;37(2):703-712.
    doi: 10.1111/jvim.16650pubmed: 36840433google scholar: lookup
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