• 1.

    UK Gabapentin Study Group. Gabapentin in partial epilepsy. Lancet 1990;335:11141117.

  • 2.

    Anhut H, Ashman P, Feuerstein TJ, et alGabapentin (Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. The International Gabapentin Study Group. Epilepsia 1994;35:795801.

    • Search Google Scholar
    • Export Citation
  • 3.

    Mao J, Chen LL. Gabapentin in pain management. Anesth Analg 2000;91:680687.

  • 4.

    Al-Mujadi H, A-Refai AR, Katzarov MG, et alPreemptive gabapentin reduces postoperative pain and opioid demand following thyroid surgery. Can J Anaesth 2006;53:268273.

    • Search Google Scholar
    • Export Citation
  • 5.

    Taylor CP, Gee NS, Su TZ, et alA summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res 1998;29:233249.

  • 6.

    Maneuf YP, Luo ZD, Lee K. A2D and the mechanism of action of gabapentin in the treatment of pain. Semin Cell Dev Biol 2006;17:565570.

  • 7.

    Cheng JK, Chiou LC. Mechanisms of the antinociceptive action of gabapentin. J Pharmacol Sci 2006;100:471486.

  • 8.

    Robertson SA. Managing pain in feline patients. Vet Clin North Am Small Anim Pract 2005;35:129146.

  • 9.

    Magnus L. Nonepileptic uses of gabapentin. Epilepsia 1999;40(suppl 6):S66S72.

  • 10.

    Yamaoka K, Nakagawa T, Uno T. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm 1978;6:165175.

    • Search Google Scholar
    • Export Citation
  • 11.

    Gibaldi M, Perrier D. Multicompartment models. In: Gibaldi M, ed. Multicompartment models. 2nd ed. New York: Marcell Dekker, 1982;45109.

    • Search Google Scholar
    • Export Citation
  • 12.

    Gabrielsson J, Weiner D. Pharmacokinetic principles. In: Gabrielsson J, Weiner D, eds. Pharmacokinetic and pharmacodynamic data analysis: concepts and applications. 4th ed. Stockholm: Swedish Pharmaceutical Press, 2006;11224.

    • Search Google Scholar
    • Export Citation
  • 13.

    Lam FC, Hung CT, Perrier DG. Estimation of variance for harmonic mean half-lives. J Pharm Sci 1985;74:229231.

  • 14.

    Beydoun A, Uthman BM, Sackellares JC. Gabapentin: pharmacokinetics, efficacy, and safety. Clin Neuropharmacol 1995;18:469481.

  • 15.

    Vollmer KO, von Hodenberg A, Kölle EU. Pharmacokinetics and metabolism of gabapentin in rat, dog and man. Arzneimittelforschung 1986;36:830839.

    • Search Google Scholar
    • Export Citation
  • 16.

    Radulovic LL, Türck D, Von Hodenberg A, et alDisposition of gabapentin (Neurontin) in mice, rats, dogs, and monkeys. Drug Metab Dispos 1995;23:441448.

    • Search Google Scholar
    • Export Citation
  • 17.

    Jun JH, Yaksh TL. The effect of intrathecal gabapentin and 3-isobutyl γ-aminobutyric acid on the hyperalgesia observed after thermal injury in the rat. Anesth Analg 1998;86:348354.

    • Search Google Scholar
    • Export Citation
  • 18.

    Sutton SC. Companion animal physiology and dosage form performance. Adv Drug Deliv Rev 2004;56:13831398.

  • 19.

    Backonja M, Glanzman RL. Gabapentin dosing for neuropathic pain: evidence from randomized, placebo-controlled clinical trials. Clin Ther 2003;25:81104.

    • Search Google Scholar
    • Export Citation
  • 20.

    Sivenius J, Kälviäinen R, Ylinen A, et alDouble-blind study of gabapentin in the treatment of partial seizures. Epilepsia 1991;32:539542.

    • Search Google Scholar
    • Export Citation

Advertisement

Pharmacokinetics of gabapentin in cats

Kristine T. Siao BS1, Bruno H. Pypendop DrMedVet, DrVetSci2, and Jan E. Ilkiw BVSc, PhD3
View More View Less
  • 1 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 2 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 3 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.

Abstract

Objective—To determine the pharmacokinetics of gabapentin in cats after IV and oral administration.

Animals—6 healthy female adult domestic shorthair cats.

Procedures—Gabapentin was administered IV (4 mg/kg) or orally (10 mg/kg) in a crossover randomized design. Blood samples were obtained immediately before gabapentin administration and at various times up to 960 minutes after IV administration or up to 1,440 minutes after oral administration. Blood samples were immediately transferred to tubes that contained EDTA and were centrifuged at 4°C. Plasma was harvested and stored at −20°C until analysis. Plasma concentrations of gabapentin were determined by use of liquid chromatography-mass spectrometry. Gabapentin concentration-time data were fit to compartment models.

Results—A 3-compartment model with elimination from the central compartment best described the disposition of gabapentin administered IV to cats, but a 1-compartment model best described the disposition of gabapentin administered orally to cats. After IV administration, the mean ± SEM apparent volume of the central compartment, apparent volume of distribution at steady state, and clearance and the harmonic mean ± jackknife pseudo-SD for terminal half-life were 90.4 ± 11.3 mL/kg, 650 ± 14 mL/kg, 3 ± 0.2 mL/min/kg, and 170 ± 21 minutes, respectively. Mean ± SD systemic availability and harmonic mean ± jackknife pseudo-SD terminal half-life after oral administration were 88.7 ± 11.1% and 177 ± 25 minutes, respectively.

Conclusions and Clinical Relevance—The disposition of gabapentin in cats was characterized by a small volume of distribution and a low clearance.

Abstract

Objective—To determine the pharmacokinetics of gabapentin in cats after IV and oral administration.

Animals—6 healthy female adult domestic shorthair cats.

Procedures—Gabapentin was administered IV (4 mg/kg) or orally (10 mg/kg) in a crossover randomized design. Blood samples were obtained immediately before gabapentin administration and at various times up to 960 minutes after IV administration or up to 1,440 minutes after oral administration. Blood samples were immediately transferred to tubes that contained EDTA and were centrifuged at 4°C. Plasma was harvested and stored at −20°C until analysis. Plasma concentrations of gabapentin were determined by use of liquid chromatography-mass spectrometry. Gabapentin concentration-time data were fit to compartment models.

Results—A 3-compartment model with elimination from the central compartment best described the disposition of gabapentin administered IV to cats, but a 1-compartment model best described the disposition of gabapentin administered orally to cats. After IV administration, the mean ± SEM apparent volume of the central compartment, apparent volume of distribution at steady state, and clearance and the harmonic mean ± jackknife pseudo-SD for terminal half-life were 90.4 ± 11.3 mL/kg, 650 ± 14 mL/kg, 3 ± 0.2 mL/min/kg, and 170 ± 21 minutes, respectively. Mean ± SD systemic availability and harmonic mean ± jackknife pseudo-SD terminal half-life after oral administration were 88.7 ± 11.1% and 177 ± 25 minutes, respectively.

Conclusions and Clinical Relevance—The disposition of gabapentin in cats was characterized by a small volume of distribution and a low clearance.

Contributor Notes

Supported by the Winn Feline Foundation.

The authors thank Scott Stanley for assistance with the gabapentin assay.

Address correspondence to Dr. Pypendop (bhpypendop@ucdavis. edu).