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Home / Equine Research Bank / J Vet Intern Med / Plasma disposition of gabapentin after the intragastric admi...
Journal of veterinary internal medicine2020; 34(2); 933-940; doi: 10.1111/jvim.15724

Plasma disposition of gabapentin after the intragastric administration of escalating doses to adult horses.

Abstract: In humans, gabapentin an analgesic, undergoes non-proportional pharmacokinetics which can alter efficacy. No information exists on the pharmacokinetics of dosages >20 mg/kg, escalating dosages or dose proportionality of gabapentin in horses. Objective: Gabapentin exposure in plasma would not increase proportionally relative to the dose in horses receiving dosages ≥20 mg/kg. To assess the plasma pharmacokinetics of gabapentin after nasogastric administration of gabapentin at dosages of 10 to 160 mg/kg in adult horses. Methods: Nine clinically healthy adult Arabian and Quarter Horses. Methods: In a randomized blinded trial, gabapentin was administered by nasogastric intubation to horses at 10, 20 mg/kg (n = 3) and 60, 80, 120, 160 mg/kg (n = 6). Plasma was collected before and at regular times over 64 hours after administration of gabapentin. Gabapentin was quantified using a validated chromatographic method. Dose proportionality was estimated using a power model. Pharmacokinetic parameters were estimated using compartmental pharmacokinetic analysis. Results: Plasma pharmacokinetics parameters of gabapentin were estimated after nasogastric administration at dosages of 10 to 160 mg/kg. Gabapentin plasma concentration increased with dose increments. However, the area under the concentration curve from zero to infinity and maximal plasma concentration did not increase proportionally relative to the dose in horses. Conclusions: Gabapentin exposure in plasma is not proportional relative to the dose in horses receiving nasogastric dosages of 10 to 160 mg/kg.
© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
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Publication Date: 2020-02-08 PubMed ID: 32034928PubMed Central: PMC7096665DOI: 10.1111/jvim.15724Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

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 assesses how the drug gabapentin is absorbed and dispersed in the blood of horses after being administered via the nose and throat at varying dosages. The results show that the level of gabapentin in the horse’s bloodstream does not proportionally increase with the dosage administered.

Objective of the Research

  • The objective of this study was to analyze how the concentration of the analgesic gabapentin, in horses’ blood, responds to different dosage increments. The researchers hypothesized that the plasma exposure of gabapentin would not increase proportionally relative to the dosage in horses receiving more than 20 mg/kg.

Research Methodology

  • Nine healthy adult Arabian and Quarter horses were chosen for this experiment.
  • The study involved a randomized blinded trial where gabapentin was administered to the horses through nasogastric intubation at dosages of 10 and 20mg/kg for 3 horses and 60, 80, 120, and 160mg/kg for the other 6.
  • Plasma samples were collected at regular intervals over a period of 64 hours after administration of gabapentin.
  • Using a validated chromatographic method, the concentration of gabapentin in the plasma was determined.
  • The researchers further worked with a power model to estimate the proportionality of the dose response.
  • The researchers segmented the data using compartmental pharmacokinetic analysis to better understand the behaviour of the drug.

Findings of the Study

  • The plasma concentration of gabapentin rose with increasing dose increments.
  • However, there was a non-proportional increase observed between the maximal plasma concentration and the area under the curve measurement (used to measure the bioavailability of the drug), with respect to the dose in horses.

Conclusion

  • The conclusion drawn from the study is that the exposure of gabapentin in the horses’ plasma does not proportionally increase with the dose. That is, higher doses do not necessarily result in a higher concentration of the drug in the bloodstream. This finding was made in horses receiving doses through the nose and throat between 10 and 160mg/kg.

Cite This Article

APA
Gold JR, Grubb TL, Green S, Cox S, Villarino NF. (2020). Plasma disposition of gabapentin after the intragastric administration of escalating doses to adult horses. J Vet Intern Med, 34(2), 933-940. https://doi.org/10.1111/jvim.15724

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 34
Issue: 2
Pages: 933-940

Researcher Affiliations

Gold, Jenifer R
  • Department of Veterinary Clinical Sciences, Washington State University, Pullman, Washington.
Grubb, Tamara L
  • Department of Veterinary Clinical Sciences, Washington State University, Pullman, Washington.
Green, Stephen
  • Department of Veterinary Clinical Sciences, Washington State University, Pullman, Washington.
Cox, Sherry
  • Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, Tennessee.
Villarino, Nicolas F
  • Department of Veterinary Clinical Sciences, Washington State University, Pullman, Washington.

MeSH Terms

  • Administration, Oral
  • Analgesics / administration & dosage
  • Analgesics / blood
  • Analgesics / pharmacokinetics
  • Animals
  • Area Under Curve
  • Dose-Response Relationship, Drug
  • Female
  • Gabapentin / administration & dosage
  • Gabapentin / blood
  • Gabapentin / pharmacokinetics
  • Horses / blood
  • Male

Conflict of Interest Statement

Authors declare no conflict of interest.

References

This article includes 41 references
  1. nhttps://www.fda.gov/drugs/drug-safety-and-availability/2019-drug-safety-communications.
  2. Honarmand A, Safavi M, Zare M. Gabapentin: An update of its pharmacological properties and therapeutic use in epilepsy.. J Res Med Sci 2011 Aug;16(8):1062-9.
    pmc: PMC3263084pubmed: 22279483
  3. Platt SR, Adams V, Garosi LS, Abramson CJ, Penderis J, De Stefani A, Matiasek L. Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy.. Vet Rec 2006 Dec 23-30;159(26):881-4.
    pubmed: 17189599
  4. Ramsay RE. Clinical efficacy and safety of gabapentin.. Neurology 1994 Jun;44(6 Suppl 5):S23-30; discussion S31-2.
    pubmed: 8022537
  5. Rose MA, Kam PC. Gabapentin: pharmacology and its use in pain management.. Anaesthesia 2002 May;57(5):451-62.
    pubmed: 11966555doi: 10.1046/j.0003-2409.2001.02399.xgoogle scholar: lookup
  6. Singh D, Kennedy DH. The use of gabapentin for the treatment of postherpetic neuralgia.. Clin Ther 2003 Mar;25(3):852-89.
    pubmed: 12852705doi: 10.1016/s0149-2918(03)80111-xgoogle scholar: lookup
  7. Jones E, Viñuela-Fernandez I, Eager RA, Delaney A, Anderson H, Patel A, Robertson DC, Allchorne A, Sirinathsinghji EC, Milne EM, MacIntyre N, Shaw DJ, Waran NK, Mayhew J, Fleetwood-Walker SM. Neuropathic changes in equine laminitis pain.. Pain 2007 Dec 5;132(3):321-331.
    pubmed: 17935886doi: 10.1016/j.pain.2007.08.035google scholar: lookup
  8. Gilron I, Baron R, Jensen T. Neuropathic pain: principles of diagnosis and treatment.. Mayo Clin Proc 2015 Apr;90(4):532-45.
    pubmed: 25841257doi: 10.1016/j.mayocp.2015.01.018google scholar: lookup
  9. Aghighi SA, Tipold A, Piechotta M, Lewczuk P, Kästner SB. Assessment of the effects of adjunctive gabapentin on postoperative pain after intervertebral disc surgery in dogs.. Vet Anaesth Analg 2012 Nov;39(6):636-46.
    pubmed: 22882632doi: 10.1111/j.1467-2995.2012.00769.xgoogle scholar: lookup
  10. Crociolli GC, Cassu RN, Barbero RC, Rocha TL, Gomes DR, Nicácio GM. Gabapentin as an adjuvant for postoperative pain management in dogs undergoing mastectomy.. J Vet Med Sci 2015 Aug;77(8):1011-5.
    pmc: PMC4565804pubmed: 25816802doi: 10.1292/jvms.14-0602google scholar: lookup
  11. Wagner AE, Mich PM, Uhrig SR, Hellyer PW. Clinical evaluation of perioperative administration of gabapentin as an adjunct for postoperative analgesia in dogs undergoing amputation of a forelimb.. J Am Vet Med Assoc 2010 Apr 1;236(7):751-6.
    pubmed: 20367041doi: 10.2460/javma.236.7.751google scholar: lookup
  12. Kukanich B, Cohen RL. Pharmacokinetics of oral gabapentin in greyhound dogs.. Vet J 2011 Jan;187(1):133-5.
    pmc: PMC2891228pubmed: 19854080doi: 10.1016/j.tvjl.2009.09.022google scholar: lookup
  13. Vollmer KO, von Hodenberg A, Kölle EU. Pharmacokinetics and metabolism of gabapentin in rat, dog and man.. Arzneimittelforschung 1986 May;36(5):830-9.
    pubmed: 3730018
  14. Adrian D, Papich MG, Baynes R, Stafford E, Lascelles BDX. The pharmacokinetics of gabapentin in cats.. J Vet Intern Med 2018 Nov;32(6):1996-2002.
    pmc: PMC6271300pubmed: 30307652doi: 10.1111/jvim.15313google scholar: lookup
  15. van Haaften KA, Forsythe LRE, Stelow EA, Bain MJ. Effects of a single preappointment dose of gabapentin on signs of stress in cats during transportation and veterinary examination.. J Am Vet Med Assoc 2017 Nov 15;251(10):1175-1181.
    pubmed: 29099247doi: 10.2460/javma.251.10.1175google scholar: lookup
  16. Siao KT, Pypendop BH, Ilkiw JE. Pharmacokinetics of gabapentin in cats.. Am J Vet Res 2010 Jul;71(7):817-21.
    pubmed: 20594085doi: 10.2460/ajvr.71.7.817google scholar: lookup
  17. KuKanich B. Outpatient oral analgesics in dogs and cats beyond nonsteroidal antiinflammatory drugs: an evidence-based approach.. Vet Clin North Am Small Anim Pract 2013 Sep;43(5):1109-25.
    pubmed: 23890242doi: 10.1016/j.cvsm.2013.04.007google scholar: lookup
  18. Davis JL, Posner LP, Elce Y. Gabapentin for the treatment of neuropathic pain in a pregnant horse.. J Am Vet Med Assoc 2007 Sep 1;231(5):755-8.
    pubmed: 17764439doi: 10.2460/javma.231.5.755google scholar: lookup
  19. Dirikolu L, Dafalla A, Ely KJ, Connerly AL, Jones CN, ElkHoly H, Lehner AF, Thompson K, Tobin T. Pharmacokinetics of gabapentin in horses.. J Vet Pharmacol Ther 2008 Apr;31(2):175-7.
    pubmed: 18307511doi: 10.1111/j.1365-2885.2008.00943.xgoogle scholar: lookup
  20. Terry RL, McDonnell SM, Van Eps AW, Soma LR, Liu Y, Uboh CE, Moate PJ, Driessen B. Pharmacokinetic profile and behavioral effects of gabapentin in the horse.. J Vet Pharmacol Ther 2010 Oct;33(5):485-94.
    pubmed: 20840393doi: 10.1111/j.1365-2885.2010.01161.xgoogle scholar: lookup
  21. Caldwell FJ, Taintor J, Waguespack RW, Sellers G, Johnson J, Lin HC. Effect of PO administration on gabapentin in chronic lameness in horses. J Equine Vet Sci 2015;35(6):536‐540.
  22. Guedes A. How to provide pain relief for laminitis in the field. AAEP Proc 2013;59:467‐468.
  23. Dutton DW, Lashnits KJ, Wegner K. Managing severe hoof pain in a horse using multimodal analgesia and a modified composite pain score. Equine Vet Educ 2009;21:37‐43.
  24. Stewart BH, Kugler AR, Thompson PR, Bockbrader HN. A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma.. Pharm Res 1993 Feb;10(2):276-81.
    pubmed: 8456077doi: 10.1023/a:1018951214146google scholar: lookup
  25. McLean MJ. Clinical pharmacokinetics of gabapentin.. Neurology 1994 Jun;44(6 Suppl 5):S17-22; discussion S31-2.
    pubmed: 8022536
  26. Woodward AD, Holcombe SJ, Steibel JP, Staniar WB, Colvin C, Trottier NL. Cationic and neutral amino acid transporter transcript abundances are differentially expressed in the equine intestinal tract.. J Anim Sci 2010 Mar;88(3):1028-33.
    pubmed: 19933436doi: 10.2527/jas.2009-2406google scholar: lookup
  27. Lerche P, Muir WM. Perioperative pain management. In: Muir WM, JAE H, eds. Equine Anesthesia Monitoring and Emergency Therapy. 2nd ed. St Louis, MO: Saunders, Elsevier; 2009:369‐380.
  28. Mayhew IG. Neurologic evaluation. In: Mayhew IG, ed. Large Animal Neurology, Philadelphia, PA: Lea and Fabiger; 1989.
  29. Mercolini L, Mandrioli R, Amore M, Raggi MA. Simultaneous HPLC-F analysis of three recent antiepileptic drugs in human plasma.. J Pharm Biomed Anal 2010 Sep 21;53(1):62-7.
    pubmed: 20363577doi: 10.1016/j.jpba.2010.02.036google scholar: lookup
  30. Gabrielsson J, Weiner D. Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications. 4th ed. Sweden, Swedish Pharmaceutical Press; 2007.
  31. Buoen C, Bjerrum OJ, Thomsen MS. How first-time-in-human studies are being performed: a survey of phase I dose-escalation trials in healthy volunteers published between 1995 and 2004.. J Clin Pharmacol 2005 Oct;45(10):1123-36.
    pubmed: 16172177doi: 10.1177/0091270005279943google scholar: lookup
  32. Hummel J, McKendrick S, Brindley C, French R. Exploratory assessment of dose proportionality: review of current approaches and proposal for a practical criterion.. Pharm Stat 2009 Jan-Mar;8(1):38-49.
    pubmed: 18386766doi: 10.1002/pst.326google scholar: lookup
  33. Smith BP, Vandenhende FR, DeSante KA, Farid NA, Welch PA, Callaghan JT, Forgue ST. Confidence interval criteria for assessment of dose proportionality.. Pharm Res 2000 Oct;17(10):1278-83.
    pubmed: 11145235doi: 10.1023/a:1026451721686google scholar: lookup
  34. Shugarts S, Benet LZ. The role of transporters in the pharmacokinetics of orally administered drugs.. Pharm Res 2009 Sep;26(9):2039-54.
    pmc: PMC2719753pubmed: 19568696doi: 10.1007/s11095-009-9924-0google scholar: lookup
  35. Lockwood PA, Cook JA, Ewy WE, Mandema JW. The use of clinical trial simulation to support dose selection: application to development of a new treatment for chronic neuropathic pain.. Pharm Res 2003 Nov;20(11):1752-9.
    pubmed: 14661918doi: 10.1023/b:pham.0000003371.32474.eegoogle scholar: lookup
  36. Jackson CD, Clanahan MJ, Joglekar K, Decha-Umphai ST. Hold the Gaba: A Case of Gabapentin-induced Hepatotoxicity.. Cureus 2018 Mar 4;10(3):e2269.
    pmc: PMC6093755pubmed: 30128217doi: 10.7759/cureus.2269google scholar: lookup
  37. Zand L, McKian KP, Qian Q. Gabapentin toxicity in patients with chronic kidney disease: a preventable cause of morbidity.. Am J Med 2010 Apr;123(4):367-73.
    pubmed: 20362757doi: 10.1016/j.amjmed.2009.09.030google scholar: lookup
  38. Raouf M, Atkinson TJ, Crumb MW, Fudin J. Rational dosing of gabapentin and pregabalin in chronic kidney disease.. J Pain Res 2017;10:275-278.
    pmc: PMC5291335pubmed: 28184168doi: 10.2147/jpr.s130942google scholar: lookup
  39. Gunson DE, Soma LR. Renal papillary necrosis in horses after phenylbutazone and water deprivation.. Vet Pathol 1983 Sep;20(5):603-10.
    pubmed: 6636467doi: 10.1177/030098588302000512google scholar: lookup
  40. Read WK. Renal medullary crest necrosis associated with phenylbutazone therapy in horses.. Vet Pathol 1983 Nov;20(6):662-9.
    pubmed: 6649337doi: 10.1177/030098588302000602google scholar: lookup
  41. Zullian C, Menozzi A, Pozzoli C, Poli E, Bertini S. Effects of α2-adrenergic drugs on small intestinal motility in the horse: an in vitro study.. Vet J 2011 Mar;187(3):342-6.
    pubmed: 20093057doi: 10.1016/j.tvjl.2009.12.015google scholar: lookup

Citations

This article has been cited 3 times.
  1. Gold JR, Grubb TL, Cox S, Malavasi L, Villarino NL. Pharmacokinetics and pharmacodynamics of repeat dosing of gabapentin in adult horses.. J Vet Intern Med 2022 Mar;36(2):792-797.
    doi: 10.1111/jvim.16386pubmed: 35150014google scholar: lookup
  2. McReynolds CB, Yang J, Guedes A, Morisseau C, Garcia R, Knych H, Tearney C, Hamamoto B, Hwang SH, Wagner K, Hammock BD. Species Differences in Metabolism of Soluble Epoxide Hydrolase Inhibitor, EC1728, Highlight the Importance of Clinically Relevant Screening Mechanisms in Drug Development.. Molecules 2021 Aug 19;26(16).
    doi: 10.3390/molecules26165034pubmed: 34443621google scholar: lookup
  3. Slovak JE, Costa AP. A pilot study of transdermal gabapentin in cats.. J Vet Intern Med 2021 Jul;35(4):1981-1987.
    doi: 10.1111/jvim.16137pubmed: 34060655google scholar: lookup
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