Analyze Diet
Animals : an open access journal from MDPI2023; 13(12); doi: 10.3390/ani13122045

Gabapentin: Clinical Use and Pharmacokinetics in Dogs, Cats, and Horses.

Abstract: Gabapentin is an anticonvulsant drug, which presents an established clinical efficacy in human patients for the management of refractory partial seizures, secondarily generalized tonic-clonic seizures, and for the control of chronic neuropathic pain. Gabapentin was synthesized as a structural analogue of the inhibitory neurotransmitter GABA, with GABA-mimetic effects, able to cross the blood-brain barrier. In veterinary medicine, is extra-label used in combination with other treatments to control seizures when other drugs are no longer effective or become toxic or for neuropathic pain treatment and anxiety. This review aimed to clarify gabapentin use and pharmacokinetic aspects to promote conscious use in dogs, cats, and horses. In dogs, gabapentin was beneficial in the treatment of epilepsy, as well as chronic, neuropathic, and post-operative pain, as well as anxiety. In cats, it showed efficacy in post-ovariohysterectomy-related pain and in anxiety management. In horses, gabapentin has been administered as an analgesic for chronic pain management. In conclusion, when used in combination with other drugs, gabapentin can be considered an interesting therapeutic option for the treatment of neuropathic diseases and analgesia in postoperative and chronic pain. However, despite its beneficial use in different clinical settings, further trials and pharmacokinetic studies are needed for the definition of an effective dosage regimen through proper pharmacokinetic/pharmacodynamic correlation in dogs, cats, and horses.
Publication Date: 2023-06-20 PubMed ID: 37370556PubMed Central: PMC10295034DOI: 10.3390/ani13122045Google 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.
  • Journal Article
  • Review

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 paper explores the use and effective dosage of Gabapentin, a medication primarily used for seizures and chronic neuropathic pain in humans, in the treatment of animals, specifically dogs, cats, and horses. The effectiveness of Gabapentin, in combination with other drugs, to manage seizures, anxiety, and post-operative and chronic pain, is discussed. Despite its advantageous use in various clinical settings, more research is needed to determine an effective dosage protocol.

Objective of the Research

  • This research is designed to clarify the usage and pharmacokinetic aspects of Gabapentin in veterinary medicine. The primary goal is to advocate for conscious usage of Gabapentin in dogs, cats, and horses, focusing on various cases like epilepsy, anxiety and chronic or post-operative pain management.

What is Gabapentin?

  • Gabapentin is an anticonvulsant drug which exhibits established clinical efficacy in human patients, for managing refractory partial seizures, secondarily generalized tonic-clonic seizures, and chronic neuropathic pain.
  • It was originally developed as a structural analogue of the inhibitory neurotransmitter GABA, with effects similar to GABA. One key property of Gabapentin is its ability to cross the blood-brain barrier, making it particularly effective in dealing with neurological issues.

Gabapentin use in Veterinary Medicine

  • In veterinary medicine, Gabapentin is primarily used as an adjunct treatment to control seizures when other drugs are no longer effective or become toxic. It’s also used for neuropathic pain treatment and management of anxiety in animals.
  • The research summarizes the use of Gabapentin in the treatment of dogs, cats, and horses. For dogs, the Gabapentin has shown to be beneficial in the treatment of epilepsy, chronic pain, neuropathic pain, post-operative pain, and anxiety.
  • For cats, Gabapentin has shown efficacy in managing post-ovariohysterectomy-related pain and in anxiety management. As for horses, Gabapentin has been administered as an analgesic for chronic pain management.

Conclusion and Future Research

  • Through this study, Gabapentin has shown promise as a combined therapeutic option for the treatment of neuropathic diseases and for analgesia in postoperative and chronic pain in dogs, cats, and horses.
  • Despite the existing evidence, the research concludes that more trials and pharmacokinetic studies need to be conducted for the definition of an effective dosage regimen through a proper correlation of pharmacokinetics and pharmacodynamics in dogs, cats, and horses.

Cite This Article

APA
Di Cesare F, Negro V, Ravasio G, Villa R, Draghi S, Cagnardi P. (2023). Gabapentin: Clinical Use and Pharmacokinetics in Dogs, Cats, and Horses. Animals (Basel), 13(12). https://doi.org/10.3390/ani13122045

Publication

ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 13
Issue: 12

Researcher Affiliations

Di Cesare, Federica
  • Department of Veterinary Medicine and Animal Sciences, Università degli Studi di Milano, Via dell'Università 6, 26900 Lodi, Italy.
Negro, Viviana
  • Department of Veterinary Medicine and Animal Sciences, Università degli Studi di Milano, Via dell'Università 6, 26900 Lodi, Italy.
Ravasio, Giuliano
  • Department of Veterinary Medicine and Animal Sciences, Università degli Studi di Milano, Via dell'Università 6, 26900 Lodi, Italy.
Villa, Roberto
  • Department of Veterinary Medicine and Animal Sciences, Università degli Studi di Milano, Via dell'Università 6, 26900 Lodi, Italy.
Draghi, Susanna
  • Department of Veterinary Medicine and Animal Sciences, Università degli Studi di Milano, Via dell'Università 6, 26900 Lodi, Italy.
Cagnardi, Petra
  • Department of Veterinary Medicine and Animal Sciences, Università degli Studi di Milano, Via dell'Università 6, 26900 Lodi, Italy.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 108 references
  1. Rose M.A., Kam P.C.A.. Gabapentin: Pharmacology and its use in pain management.. Anaesthesia 2002;57:451–462.
  2. Pubchem. [(accessed on 1 April 2023)]; Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Gabapentin.
  3. Tanabe M., Takasu K., Kasuya N., Shimizu S., Honda M., Ono H.. Role of descending noradrenergic system and spinal α2 -adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse.. Br. J. Pharmacol. 2005;144:703–714.
    doi: 10.1038/sj.bjp.0706109pmc: PMC1576051pubmed: 15678083google scholar: lookup
  4. Ramsay R.E.. Clinical efficacy and safety of gabapentin.. Neurology 1994;44:S23–S30.
    pubmed: 8022537
  5. Taylor C.P.. Emerging perspectives on the mechanism of action of gabapentin.. Neurology 1994;44:S10–S16.
    pubmed: 7517515
  6. Beydoun A., Uthman B.M., Sackellares C.J.. Gabapentin Pharmacokinetics, Efficacy, and Safety.. Clin. Neuropharmacol. 1995;18:469–481.
  7. O’Connor A.B., Dworkin R.H.. Treatment of Neuropathic Pain: An Overview of Recent Guidelines.. Am. J. Med. 2009;122:S22–S32.
    doi: 10.1016/j.amjmed.2009.04.007pubmed: 19801049google scholar: lookup
  8. Peckham A.M., Evoy K.E., Ochs L., Covvey J.R.. Gabapentin for Off-Label Use: Evidence-Based or Cause for Concern?. Subst. Abus. Res. Treat. 2018;12:117822181880131.
    doi: 10.1177/1178221818801311pmc: PMC6153543pubmed: 30262984google scholar: lookup
  9. Russo M., Graham B., Santarelli D.M.. Gabapentin—Friend or foe?. Pain Pract. 2023;23:63–69.
    doi: 10.1111/papr.13165pmc: PMC10092611pubmed: 36300903google scholar: lookup
  10. Govendir M., Perkins M., Malik R.. Improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent.. Aust. Veter J. 2005;83:602–608.
  11. Platt S.R., Adams V., Garosi L., Abramson C.J., Penderis J., De Stefani A., Matiasek L.. Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy.. Veter Rec. 2006;159:881–884.
    pubmed: 17189599
  12. Plessas I.N., Volk H.A., Rusbridge C., Vanhaesebrouck A., Jeffery N.. Comparison of gabapentin versus topiramate on clinically affected dogs with Chiari-like malformation and syringomyelia.. Veter Rec. 2015;177:288.
    doi: 10.1136/vr.103234pubmed: 26269418google scholar: lookup
  13. Ruel H.L.M., Watanabe R., Evangelista M.C., Beauchamp G., Auger J.-P., Segura M., Steagall P.V.. Pain burden, sensory profile and inflammatory cytokines of dogs with naturally-occurring neuropathic pain treated with gabapentin alone or with meloxicam.. PLoS ONE 2020;15:e0237121.
  14. Brioschi F.A., Di Cesare F., Gioeni D., Rabbogliatti V., Ferrari F., D’urso E.S., Amari M., Ravasio G.. Oral Transmucosal Cannabidiol Oil Formulation as Part of a Multimodal Analgesic Regimen: Effects on Pain Relief and Quality of Life Improvement in Dogs Affected by Spontaneous Osteoarthritis.. Animals 2020;10:1505.
    doi: 10.3390/ani10091505pmc: PMC7552307pubmed: 32858828google scholar: lookup
  15. Bleuer-Elsner S., Medam T., Masson S.. Effects of a single oral dose of gabapentin on storm phobia in dogs: A double-blind, placebo-controlled crossover trial.. Veter Rec. 2021;189:e453.
    doi: 10.1002/vetr.453pubmed: 33993491google scholar: lookup
  16. Stollar O.O., Moore G.E., Mukhopadhyay A., Gwin W., Ogata N.. Effects of a single dose of orally administered gabapentin in dogs during a veterinary visit: A double-blinded, placebo-controlled study.. J. Am. Veter Med. Assoc. 2022;260:1–10.
    doi: 10.2460/javma.21.03.0167pubmed: 35358063google scholar: lookup
  17. Fantinati M., Trnka J., Signor A., Dumond S., Jourdan G., Verwaerde P., Priymenko N.. Appetite-stimulating effect of gabapentin vs. mirtazapine in healthy cats post-ovariectomy.. J. Feline Med. Surg. 2020;22:1176–1183.
    doi: 10.1177/1098612X20916391pmc: PMC10814375pubmed: 32462966google scholar: lookup
  18. Steagall B.P.M., Benito J., Monteiro B.P., Doodnaught G.M., Beauchamp G., Evangelista M.C.. Analgesic effects of gabapentin and buprenorphine in cats undergoing ovariohysterectomy using two pain-scoring systems: A randomized clinical trial.. J. Feline Med. Surg. 2018;20:741–748.
    doi: 10.1177/1098612X17730173pmc: PMC11104130pubmed: 28920534google scholar: lookup
  19. Pankratz K.E., Ferris K.K., Griffith E.H., Sherman B.L.. Use of single-dose oral gabapentin to attenuate fear responses in cage-trap confined community cats: A double-blind, placebo-controlled field trial.. J. Feline Med. Surg. 2018;20:535–543.
    doi: 10.1177/1098612X17719399pmc: PMC11104070pubmed: 28718700google scholar: lookup
  20. Van Haaften K.A., Forsythe L.R.E., Stelow E.A., Bain M.J.. Effects of a single preappointment dose of gabapentin on signs of stress in cats during transportation and veterinary examination.. J. Am. Veter Med. Assoc. 2017;251:1175–1181.
    doi: 10.2460/javma.251.10.1175pubmed: 29099247google scholar: lookup
  21. Gurney M., Gower L.. Randomised clinical trial evaluating the effect of a single preappointment dose of gabapentin on signs of stress in hyperthyroid cats.. J. Feline Med. Surg. 2022;24:e85–e89.
    doi: 10.1177/1098612X221091736pmc: PMC9160945pubmed: 35481442google scholar: lookup
  22. Allen M.E., LeBlanc N.L., Scollan K.F.. Hemodynamic, Echocardiographic, and Sedative Effects of Oral Gabapentin in Healthy Cats.. J. Am. Anim. Hosp. Assoc. 2021;57:278–284.
    doi: 10.5326/JAAHA-MS-7081pubmed: 34606579google scholar: lookup
  23. Lanneau C., Green A., Hirst W.D., Wise A., Brown J.T., Donnier E., Charles K.J., Wood M., Davies C.H., Pangalos M.N.. Gabapentin is not a GABAB receptor agonist.. Neuropharmacology 2001;41:965–975.
    doi: 10.1016/S0028-3908(01)00140-Xpubmed: 11747901google scholar: lookup
  24. Gee N.S., Brown J.P., Dissanayake V.U.K., Offord J., Thurlow R., Woodruff G.N.. The Novel Anticonvulsant Drug, Gabapentin (Neurontin), Binds to the α2δ Subunit of a Calcium Channel.. J. Biol. Chem. 1996;271:5768–5776.
    doi: 10.1074/jbc.271.10.5768pubmed: 8621444google scholar: lookup
  25. Radulovic L.L., Türck D., Von Hodenberg A., Vollmer K.O., McNally W.P., Dehart P.D., Hanson B.J., Bockbrader H.N., Chang T.. Disposition of gabapentin (neurontin) in mice, rats, dogs, and monkeys.. Drug Metab. Dispos. 1995;23:441–448.
    pubmed: 7600909
  26. Dewey C.W.. Anticonvulsant Therapy in Dogs and Cats.. Veter Clin. North Am. Small Anim. Pract. 2006;36:1107–1127.
    doi: 10.1016/j.cvsm.2006.05.005pubmed: 16984829google scholar: lookup
  27. Goa K.L., Sorkin E.M.. Gabapentin: A Review of Its Pharmacological Properties and Clinical Potential in Epilepsy.. Drugs 1993;46:409–427.
  28. Patel M.K., Gonzalez M.I., Bramwell S., Pinnock R.D., Lee K.. Gabapentin inhibits excitatory synaptic transmission in the hyperalgesic spinal cord.. Br. J. Pharmacol. 2000;130:1731–1734.
    doi: 10.1038/sj.bjp.0703530pmc: PMC1572282pubmed: 10952660google scholar: lookup
  29. Hill D.R., Suman-Chauhan N., Woodruff G.N.. Localization of [3H]gabapentin to a novel site in rat brain: Autoradiographic studies.. Eur. J. Pharmacol. 1993;244:303–309.
    doi: 10.1016/0922-4106(93)90156-4pubmed: 8384571google scholar: lookup
  30. Sills G.J., Rogawski M.A.. Mechanisms of action of currently used antiseizure drugs.. Neuropharmacology 2020;168:107966.
  31. Muñana K.R.. Management of Refractory Epilepsy.. Top. Companion Anim. Med. 2013;28:67–71.
    doi: 10.1053/j.tcam.2013.06.007pubmed: 24070684google scholar: lookup
  32. Gordon D.B., Love G.. Pharmacologic management of neuropathic pain.. Pain Manag. Nurs. 2004;5:19–33.
    doi: 10.1016/j.pmn.2004.10.005pubmed: 15644856google scholar: lookup
  33. Jensen T.S., Gottrup H., Sindrup S.H., Bach F.W.. The clinical picture of neuropathic pain.. Eur. J. Pharmacol. 2001;429:1–11.
    doi: 10.1016/S0014-2999(01)01302-4pubmed: 11698022google scholar: lookup
  34. Bennett D.L.H.. Informed drug choices for neuropathic pain.. Lancet Neurol. 2015;14:129–130.
    doi: 10.1016/S1474-4422(14)70329-1pubmed: 25575709google scholar: lookup
  35. Walters E.T.. Neuroinflammatory contributions to pain after SCI: Roles for central glial mechanisms and nociceptor-mediated host defense.. Exp. Neurol. 2014;258:48–61.
  36. Moore S.A.. Managing Neuropathic Pain in Dogs.. Front. Veter Sci. 2016;3:12.
    doi: 10.3389/fvets.2016.00012pmc: PMC4762016pubmed: 26942185google scholar: lookup
  37. Epstein M., Rodan I., Griffenhagen G., Kadrlik J., Petty M., Robertson S., Simpson W.. AAHA/AAFP Pain Management Guidelines for Dogs and Cats.. J. Am. Anim. Hosp. Assoc. 2015;51:67–84.
    doi: 10.5326/JAAHA-MS-7331pubmed: 25764070google scholar: lookup
  38. Mathews K., Kronen P.W., Lascelles D., Nolan A., Robertson S., Steagall P.V., Wright B., Yamashita K.. Guidelines for Recognition, Assessment and Treatment of Pain.. J. Small Anim. Pract. 2014;55:E10–E68.
    doi: 10.1111/jsap.12200pubmed: 24841489google scholar: lookup
  39. Wolfe K.C., Poma R.. Syringomyelia in the Cavalier King Charles spaniel (CKCS) dog.. Can. Vet. J. 2010;51:95–102.
    pmc: PMC2797361pubmed: 20357949
  40. Guedes A.G.P., Meadows J.M., Pypendop B.H., Johnson E.G., Zaffarano B.. Assessment of the effects of gabapentin on activity levels and owner-perceived mobility impairment and quality of life in osteoarthritic geriatric cats.. J. Am. Veter Med. Assoc. 2018;253:579–585.
    doi: 10.2460/javma.253.5.579pubmed: 30110208google scholar: lookup
  41. Lorenz N.D., Comerford E.J., Iff I.. Long-term use of gabapentin for musculoskeletal disease and trauma in three cats.. J. Feline Med. Surg. 2013;15:507–512.
    doi: 10.1177/1098612X12470828pmc: PMC10816316pubmed: 23253881google scholar: lookup
  42. Vettorato E., Corletto F.. Gabapentin as part of multi-modal analgesia in two cats suffering multiple injuries.. Veter-Anaesth. Analg. 2011;38:518–520.
  43. Young J.M., Schoonover M.J., Kembel S.L., Taylor J.D., Bauck A.G., Gilliam L.L.. Efficacy of orally administered gabapentin in horses with chronic thoracic limb lameness.. Veter Anaesth. Analg. 2020;47:259–266.
    doi: 10.1016/j.vaa.2019.11.003pubmed: 31980368google scholar: lookup
  44. Readford P.K., Lester G.D., Secombe C.J.. Temporohyoid osteoarthropathy in two young horses.. Aust. Veter J. 2013;91:209–212.
    doi: 10.1111/avj.12039pubmed: 23614517google scholar: lookup
  45. Davis J.L., Posner L.P., Elce Y.. Gabapentin for the treatment of neuropathic pain in a pregnant horse.. J. Am. Veter Med. Assoc. 2007;231:755–758.
    doi: 10.2460/javma.231.5.755pubmed: 17764439google scholar: lookup
  46. Luo Z.D., Chaplan S.R., Higuera E.S., Sorkin L.S., Stauderman K.A., Williams M.E., Yaksh T.L.. Upregulation of Dorsal Root Ganglion α2δ Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats.. J. Neurosci. 2001;21:1868–1875.
  47. Witcher D.R., De Waard M., Sakamoto J., Franzini-Armstrong C., Pragnell M., Kahl S.D., Campbell K.P.. Subunit Identification and Reconstitution of the N-Type Ca2+ Channel Complex Purified from Brain.. Science 1993;261:486–489.
    doi: 10.1126/science.8392754pubmed: 8392754google scholar: lookup
  48. Sutton K.G., Martin D.J., Pinnock R.D., Lee K., Scott R.H.. Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones.. Br. J. Pharmacol. 2002;135:257–265.
    doi: 10.1038/sj.bjp.0704439pmc: PMC1573104pubmed: 11786502google scholar: lookup
  49. Suto T., Severino A.L., Eisenach J.C., Hayashida K.-I.. Gabapentin increases extracellular glutamatergic level in the locus coeruleus via astroglial glutamate transporter-dependent mechanisms.. Neuropharmacology 2014;81:95–100.
  50. Hayashida K.-I., Obata H., Nakajima K., Eisenach J.C.. Gabapentin Acts within the Locus Coeruleus to Alleviate Neuropathic Pain.. Anesthesiology 2008;109:1077–1084.
  51. Yoshizumi M., Parker R.A., Eisenach J.C., Hayashida K.-I.. Gabapentin Inhibits γ-Amino Butyric Acid Release in the Locus Coeruleus but Not in the Spinal Dorsal Horn after Peripheral Nerve Injury in Rats.. Anesthesiology 2012;116:1347–1353.
  52. Takasu K., Ono H., Tanabe M.. Gabapentin produces PKA-dependent pre-synaptic inhibition of GABAergic synaptic transmission in LC neurons following partial nerve injury in mice.. J. Neurochem. 2008;105:933–942.
  53. Hayashida K.-I., Obata H.. Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory System.. Int. J. Mol. Sci. 2019;20:822.
    doi: 10.3390/ijms20040822pmc: PMC6412536pubmed: 30769838google scholar: lookup
  54. Laughlin T.M., Tram K.V., Wilcox G.L., Birnbaum A.K.. Comparison of antiepileptic drugs tiagabine, lamotrigine, and gabapentin in mouse models of acute, prolonged, and chronic nociception.. J. Pharmacol. Exp. Ther. 2002;302:1168–1175.
    doi: 10.1124/jpet.302.3.1168pubmed: 12183677google scholar: lookup
  55. Field M., Oles R.J., Lewis S., McCleary S., Hughes J., Singh L.. Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective antihyperalgesic agents.. Br. J. Pharmacol. 1997;121:1513–1522.
    doi: 10.1038/sj.bjp.0701320pmc: PMC1564875pubmed: 9283683google scholar: lookup
  56. Wagner A.E., Mich P.M., Uhrig S.R., Hellyer P.W.. Clinical evaluation of perioperative administration of gabapentin as an adjunct for postoperative analgesia in dogs undergoing amputation of a forelimb.. J. Am. Veter Med. Assoc. 2010;236:751–756.
    doi: 10.2460/javma.236.7.751pubmed: 20367041google scholar: lookup
  57. Aghighi S.A., Tipold A., Piechotta M., Lewczuk P., Kästner S.B.. Assessment of the effects of adjunctive gabapentin on postoperative pain after intervertebral disc surgery in dogs.. Veter Anaesth. Analg. 2012;39:636–646.
  58. Crociolli G.C., Cassu R.N., Barbero R.C., Rocha T.L.A., Gomes D.R., Nicácio G.M.. Gabapentin as an adjuvant for postoperative pain management in dogs undergoing mastectomy.. J. Veter Med. Sci. 2015;77:1011–1015.
    doi: 10.1292/jvms.14-0602pmc: PMC4565804pubmed: 25816802google scholar: lookup
  59. Singh L., Field M.J., Ferris P., Hunter J.C., Oles R.J., Williams R.G., Woodruff G.N.. The antiepileptic agent gabapentin (Neurontin) possesses anxiolytic-like and antinociceptive actions that are reversed byd-serine.. Psychopharmacology 1996;127:1–9.
    doi: 10.1007/BF02805968pubmed: 8880937google scholar: lookup
  60. Sethi A., Das B.P., Bajaj B.K.. The Anxiolytic Activity of Gabapentin in Mice.. J. Appl. Res. 2005;5:415–422.
  61. Erfurth A., Kammerer C., Grunze H., Normann C., Walden J.. An open label study of gabapentin in the treatment of acute mania.. J. Psychiatr. Res. 1998;32:261–264.
    doi: 10.1016/S0022-3956(98)00010-7pubmed: 9789203google scholar: lookup
  62. Schaffer B., Schaffer L.. Gabapentin in the Treatment of Bipolar Disorder.. Am. J. Psychiatry 1997;154:291–292.
    pubmed: 9016291
  63. Hatzimanolis J., Lykouras L., Oulis P., Christodoulou G.N., Oulis P.. Gabapentin as monotherapy in the treatment of acute mania.. Eur. Neuropsychopharmacol. 1999;9:257–258.
    doi: 10.1016/S0924-977X(98)00034-0pubmed: 10208297google scholar: lookup
  64. Pollack M.H., Matthews J., Scott E.L.. Gabapentin as a Potential Treatment for Anxiety Disorders.. Am. J. Psychiatry. 1998;155:992–993.
    doi: 10.1176/ajp.155.7.992pubmed: 9659873google scholar: lookup
  65. Hong J.S.W., Atkinson L.Z., Al-Juffali N., Awad A., Geddes J.R., Tunbridge E.M., Harrison P.J., Cipriani A.. Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale.. Mol. Psychiatry. 2022;27:1339–1349.
    doi: 10.1038/s41380-021-01386-6pmc: PMC9095464pubmed: 34819636google scholar: lookup
  66. Garakani A., Murrough J.W., Freire R.C., Thom R.P., Larkin K., Buono F.D., Iosifescu D.V.. Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options.. Front. Psychiatry. 2020;11:595584.
    doi: 10.3389/fpsyt.2020.595584pmc: PMC7786299pubmed: 33424664google scholar: lookup
  67. Platt M.K., Adams V., Garosi L.S.. Gabapentin as Adjunctive Therapy for Refractory Idiopathic Epilepsy in Dogs; Proceedings of the 16th Annual European College of Veterinary Neurologist Symposium (Prague). Prague, Czech Republic. 20 February 2003.
  68. Ghaffari M.S., Moghaddassi A.P., Khorami N.. Successful management of refractory psychomotor seizures with gabapentin and phenobarbital in a Doberman pinscher dog.. Comp. Clin. Pathol. 2010;19:125–127.
    doi: 10.1007/s00580-009-0898-4google scholar: lookup
  69. Dewey C.W., Berg J.M., Barone G., Marino D.J., Stefanacci J.D.. Foramen magnum decompression for treatment of caudal occipital malformation syndrome in dogs.. J. Am. Veter Med. Assoc. 2005;227:1270–1275.
    doi: 10.2460/javma.2005.227.1270pubmed: 16266016google scholar: lookup
  70. Kaya F.N., Yavascaoglu B., Baykara M., Altun G.T., Gülhan N., Ata F.. Effect of oral gabapentin on the intraocular pressure and haemodynamic responses induced by tracheal intubation.. Acta Anaesthesiol. Scand. 2008;52:1076–1080.
  71. Memiş D., Turan A., Karamanloğlu B., Şeker Ş., Türe M.. Gabapentin reduces cardiovascular responses to laryngoscopy and tracheal intubation.. Eur. J. Anaesthesiol. 2006;23:686–690.
    doi: 10.1017/S0265021506000500pubmed: 16805934google scholar: lookup
  72. Bala I., Bharti N., Ramesh N.P.. Effect of gabapentin pretreatment on the hemodynamic response to laryngoscopy and tracheal intubation in treated hypertensive patients.. Acta Anaesthesiol. Taiwanica. 2015;53:95–98.
    doi: 10.1016/j.aat.2015.07.004pubmed: 26314902google scholar: lookup
  73. Trbolova A., Ghaffari M.S., Capik I.. Effects of premedication with oral gabapentin on intraocular pressure changes following tracheal intubation in clinically normal dogs.. BMC Veter Res. 2017;13:288.
    doi: 10.1186/s12917-017-1206-1pmc: PMC5605971pubmed: 28927402google scholar: lookup
  74. Shukla A.K., Pinard C.L., Flynn B.L., Bauman C.A.. Effects of orally administered gabapentin, tramadol, and meloxicam on ocular variables in healthy dogs.. Am. J. Veter Res. 2020;81:973–984.
    doi: 10.2460/ajvr.81.12.973pubmed: 33251843google scholar: lookup
  75. Johnson B.A., Aarnes T.K., Wanstrath A.W., Pereira C.H.R., Bednarski R.M., Lerche P., McLoughlin M.A.. Effect of oral administration of gabapentin on the minimum alveolar concentration of isoflurane in dogs.. Am. J. Veter Res. 2019;80:1007–1011.
    doi: 10.2460/ajvr.80.11.1007pubmed: 31644338google scholar: lookup
  76. Bhatti S.F., De Risio L., Muñana K., Penderis J., Stein V.M., Tipold A., Berendt M., Farquhar R.G., Fischer A., Long S.. International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe.. BMC Veter Res. 2015;11:176.
    doi: 10.1186/s12917-015-0464-zpmc: PMC4552371pubmed: 26316233google scholar: lookup
  77. Steagall P.V., Steagall B.P.M.. Multimodal analgesia for perioperative pain in three cats.. J. Feline Med. Surg. 2013;15:737–743.
    doi: 10.1177/1098612X13476033pmc: PMC11191706pubmed: 23382595google scholar: lookup
  78. Slovak J.E., Costa A.P.. A pilot study of transdermal gabapentin in cats.. J. Veter Intern. Med. 2021;35:1981–1987.
    doi: 10.1111/jvim.16137pmc: PMC8295683pubmed: 34060655google scholar: lookup
  79. Pypendop B.H., Siao K.T., Ilkiw J.E.. Thermal antinociceptive effect of orally administered gabapentin in healthy cats.. Am. J. Veter Res. 2010;71:1027–1032.
    doi: 10.2460/ajvr.71.9.1027pubmed: 20807141google scholar: lookup
  80. Buckley L.A.. Cats that get stressed when visiting the veterinary practice: Can gabapentin help improve their welfare?. Vet. Evid. 2019;4:1–12.
    doi: 10.18849/ve.v4i4.227google scholar: lookup
  81. Erickson A., Harbin K., MacPherson J., Rundle K., Overall K.L.. A review of pre-appointment medications to reduce fear and anxiety in dogs and cats at veterinary visits.. Can. Vet. J. 2021;62:952–960.
    pmc: PMC8360309pubmed: 34475580
  82. Hudec C.P., Griffin C.E.. Changes in the stress markers cortisol and glucose before and during intradermal testing in cats after single administration of pre-appointment gabapentin.. J. Feline Med. Surg. 2020;22:138–145.
    doi: 10.1177/1098612X19830501pmc: PMC10814564pubmed: 30982420google scholar: lookup
  83. Tuleski G.L.R., Silveira M.F., Bastos R.F., Pscheidt M.J.G.R., Prieto W.D.S., Sousa M.G.. Behavioral and cardiovascular effects of a single dose of gabapentin or melatonin in cats: A randomized, double-blind, placebo-controlled trial.. J. Feline Med. Surg. 2022;24:e524–e534.
    doi: 10.1177/1098612X221124359pmc: PMC10812368pubmed: 36350565google scholar: lookup
  84. Reid P., Pypendop B.H., Ilkiw J.E.. The Effects of Intravenous Gabapentin Administration on the Minimum Alveolar Concentration of Isoflurane in Cats.. Anesth. Analg. 2010;111:633–637.
    doi: 10.1213/ANE.0b013e3181e51245pubmed: 20547821google scholar: lookup
  85. Gomes S.A., Garosi L.S., Behr S., Toni C., Tabanez J., Rusbridge C., Targett M., Lowrie M.. Clinical features, treatment and outcome of discospondylitis in cats.. J. Feline Med. Surg. 2022;24:311–321.
    doi: 10.1177/1098612X211020159pmc: PMC10812237pubmed: 34100660google scholar: lookup
  86. Jones E., Viñuela-Fernandez I., Eager R.A., Delaney A., Anderson H., Patel A., Robertson D.C., Allchorne A., Sirinathsinghji E.C., Milne E.M.. Neuropathic changes in equine laminitis pain.. Pain 2007;132:321–331.
    doi: 10.1016/j.pain.2007.08.035pubmed: 17935886google scholar: lookup
  87. Aleman M., Rhodes D., Williams D., Guedes A., Madigan J.. Sensory Evoked Potentials of the Trigeminal Nerve for the Diagnosis of Idiopathic Headshaking in a Horse.. J. Veter Intern. Med. 2014;28:250–253.
    doi: 10.1111/jvim.12237pmc: PMC4895556pubmed: 24428325google scholar: lookup
  88. Leise B.S., Faleiros R.R., Watts M., Johnson P.J., Black S.J., Belknap J.K.. Hindlimb laminar inflammatory response is similar to that present in forelimbs after carbohydrate overload in horses.. Equine Veter J. 2012;44:633–639.
  89. Gold J.R., Grubb T.L., Green S., Cox S., Villarino N.F.. Plasma disposition of gabapentin after the intragastric administration of escalating doses to adult horses.. J. Veter Intern. Med. 2020;34:933–940.
    doi: 10.1111/jvim.15724pmc: PMC7096665pubmed: 32034928google scholar: lookup
  90. Gold J.R., Grubb T.L., Cox S., Malavasi L., Villarino N.L.. Pharmacokinetics and pharmacodynamics of repeat dosing of gabapentin in adult horses.. J. Veter Intern. Med. 2022;36:792–797.
    doi: 10.1111/jvim.16386pmc: PMC8965223pubmed: 35150014google scholar: lookup
  91. Caldwell F.J., Taintor J., Waguespack R.W., Sellers G., Johnson J., Lin H.-C.. Effect of PO Administered Gabapentin on Chronic Lameness in Horses.. J. Equine Veter Sci. 2015;35:536–540.
  92. Terry R.L., McDONNELL S.M., Van Eps A.W., Soma L.R., Liu Y., Uboh C.E., Moate P.J., Driessen B.. Pharmacokinetic profile and behavioral effects of gabapentin in the horse.. J. Veter Pharmacol. Ther. 2010;33:485–494.
  93. Guedes A.. Pain Management in Horses.. Veter Clin. N. Am. Equine Pract. 2017;33:181–211.
    doi: 10.1016/j.cveq.2016.11.006pubmed: 28325179google scholar: lookup
  94. Siao K.T., Pypendop B.H., Ilkiw J.E.. Pharmacokinetics of gabapentin in cats.. Am. J. Veter Res. 2010;71:817–821.
    doi: 10.2460/ajvr.71.7.817pubmed: 20594085google scholar: lookup
  95. Adrian D., Papich M.G., Baynes R., Stafford E., Lascelles B.D.X.. The pharmacokinetics of gabapentin in cats.. J. Veter Intern. Med. 2018;32:1996–2002.
    doi: 10.1111/jvim.15313pmc: PMC6271300pubmed: 30307652google scholar: lookup
  96. KuKanich B., Cohen R.L.. Pharmacokinetics of oral gabapentin in greyhound dogs.. Veter J. 2011;187:133–135.
    doi: 10.1016/j.tvjl.2009.09.022pmc: PMC2891228pubmed: 19854080google scholar: lookup
  97. Golfar Y., Shayanfar A.. Prediction of Biopharmaceutical Drug Disposition Classification System (BDDCS) by Structural Parameters.. J. Pharm. Pharm. Sci. 2019;22:247–269.
    doi: 10.18433/jpps30271pubmed: 31287788google scholar: lookup
  98. Taylor C.P.. Mechanisms of analgesia by gabapentin and pregabalin—Calcium channel α2-δ [Cavα2-δ] ligands.. Pain 2009;142:13–16.
    doi: 10.1016/j.pain.2008.11.019pubmed: 19128880google scholar: lookup
  99. Shugarts S., Benet L.Z.. The Role of Transporters in the Pharmacokinetics of Orally Administered Drugs.. Pharm. Res. 2009;26:2039–2054.
    doi: 10.1007/s11095-009-9924-0pmc: PMC2719753pubmed: 19568696google scholar: lookup
  100. Vollmer K.O., von Hodenberg A., Kölle E.U.. Pharmacokinetics and Metabolism of Gabapentin in Rat, Dog and Man.. Arzneimittel-Forschung 1986;36:830–839.
    pubmed: 3730018
  101. Lockwood P.A., Cook J.A., Ewy W.E., Mandema J.W.. The use of clinical trial simulation to support dose selection: Application to development of a new treatment for chronic neuropathic pain.. Pharm. Res. 2003;20:1752–1759.
  102. Larsen M.S., Keizer R., Munro G., Mørk A., Holm R., Savic R., Kreilgaard M.. Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model.. Pharm. Res. 2016;33:1133–1143.
    doi: 10.1007/s11095-016-1859-7pubmed: 26780452google scholar: lookup
  103. Papich M.G.. Papich Handbook of Veterinary Drugs.. 5th ed. Elsevier eBook on VitalSource; Amsterdam, The Netherlands: 2021. pp. 398–400.
  104. Quimby J.M., Lorbach S.K., Saffire A., Kennedy A., Wittenburg L.A., Aarnes T.K., Creighton K.J., Jones S.E., Paschall R.E., King E.M.. Serum concentrations of gabapentin in cats with chronic kidney disease.. J. Feline Med. Surg. 2022;24:1260–1266.
    doi: 10.1177/1098612X221077017pmc: PMC9395545pubmed: 35195476google scholar: lookup
  105. Dirikolu L., Dafalla A., Ely K.J., Connerly A.L., Jones C.N., ElkHOLY H., Lehner A.F., Thompson K., Tobin T.. Pharmacokinetics of gabapentin in horses.. J. Veter-Pharmacol. Ther. 2008;31:175–177.
  106. Berry D.J., Beran R.G., Plunkeft M.J., Clarke L.A., Hung W.T.. The Absorption of Gabapentin Following High Dose Escalation.. Seizure 2003;12:28–36.
    doi: 10.1016/S1059131102001425pubmed: 12495646google scholar: lookup
  107. Del Amo E.M., Urtti A., Yliperttula M.. Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2.. Eur. J. Pharm. Sci. 2008;35:161–174.
    doi: 10.1016/j.ejps.2008.06.015pubmed: 18656534google scholar: lookup
  108. Stewart B.H., Kugler A.R., Thompson P.R., Bockbrader H.N.. 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;10:276–281.
    doi: 10.1023/A:1018951214146pubmed: 8456077google scholar: lookup