• 1.

    Roughan JV, Flecknell PA. Evaluation of a short duration behaviour-based post-operative pain scoring system in rats. Eur J Pain 2003;7:397406.

    • Search Google Scholar
    • Export Citation
  • 2.

    Gibson TP. Pharmacokinetics, efficacy, and safety of analgesia with a focus on tramadol HCl. Am J Med 1996;101(supp 1A):47S53S.

  • 3.

    Lehman KA. Tramadol for the management of acute pain. Drugs 1994;47(suppl 1):1932.

  • 4.

    Tramadol [package insert]. Detroit: Caraco Pharmaceutical Laboratories Ltd, 2006.

  • 5.

    Tramadol PR. Compend Contin Educ Pract Vet 2004;26:800802.

  • 6.

    Wu WN, McKown LA, Gauthier AD, et al. Metabolism of the analgesic drug, tramadol hydrochloride, in rat and dog. Xenobiotica 2001;31:423441.

    • Search Google Scholar
    • Export Citation
  • 7.

    Kukanich B, Papich MG. Pharmacokinetics of tramadol and the metabolite O-desmethyltramadol in dogs. J Vet Pharmacol Ther 2004;27:239246.

    • Search Google Scholar
    • Export Citation
  • 8.

    Plumb DC. Plumb's veterinary drug handbook. 5th ed. Ames, Iowa: Blackwell Publishing, 2005;11131114.

  • 9.

    Mastrocinque S, Fantoni DT. A comparison of preoperative tramadol and morphine for the control of early postoperative pain in canine ovariohysterectomy. Vet Anaesth Analg 2003;30:220228.

    • Search Google Scholar
    • Export Citation
  • 10.

    Natalini CC, Robinson EP. Evaluation of the analgesic effects of epidurally administered morphine, alfentanil, butorphanol, tramadol, and U50488H in horses. Am J Vet Res 2000;61:15791586.

    • Search Google Scholar
    • Export Citation
  • 11.

    Teppema LJ, Nieuwenhuijs D, Olievier CN, et al. Respiratory depression by tramadol in the cat: involvement of opioid receptors. Anesthesiology 2003;98:420427.

    • Search Google Scholar
    • Export Citation
  • 12.

    Russo CI, Wynne PM. Tramadol: metabolism and excretion in the horse, in Proceedings. 13th Int Conf Racing Analysts Vet 2001;453457.

  • 13.

    Wagner DS, Johnson CE, Cichon-Hensley BK, et al. Stability of oral liquid preparations of tramadol in strawberry syrup and a sugar-free vehicle. Am J Health Syst Pharm 2003;60:12681270.

    • Search Google Scholar
    • Export Citation
  • 14.

    Scott LJ, Perry CM. Tramadol, a review of its use in perioperative pain. Drugs 2000;60:139176.

  • 15.

    Grond S, Meuser T, Uragg H, et al. Serum concentrations of tramadol enantiomers during patient-controlled analgesia. Br J Clin Pharmacol 1999;48:254257.

    • Search Google Scholar
    • Export Citation
  • 16.

    Fernandez-Varon E, Bovaira MJ, Espuny A, et al. Pharmacokinetic-pharmacodynamic integration of moxifloxicin in rabbits after intravenous, intramuscular and oral administration. J Vet Pharmacol Ther 2005;28:343348.

    • Search Google Scholar
    • Export Citation
  • 17.

    Abd El-Aty AM, Goudah A, El-Sooud KA, et al. Pharmacokinetics and bioavailability of florfenicol following intravenous, intramuscular and oral administration in rabbits. Vet Res Commun 2004;28:515524.

    • Search Google Scholar
    • Export Citation
  • 18.

    Park BK, Lim JH, Kim MS, et al. Pharmacokinetics of florfenicol and its major metabolite, florfenicol anime, in rabbits. J Vet Pharmacol Ther 2007;30:3236.

    • Search Google Scholar
    • Export Citation
  • 19.

    Toutain PL, Reymond N, Laroute V, et al. Pharmacokinetics of meloxicam in plasma and urine of horses. Am J Vet Res 2004;65:15421547.

Advertisement

Pharmacokinetics of orally administered tramadol in domestic rabbits (Oryctolagus cuniculus)

View More View Less
  • 1 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 2 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 3 Department of Comparative Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

Abstract

Objective—To determine the pharmacokinetics of an orally administered dose of tramadol in domestic rabbits (Oryctolagus cuniculus).

Animals—6 healthy adult sexually intact female New Zealand White rabbits.

Procedures—Physical examinations and plasma biochemical analyses were performed to ensure rabbits were healthy prior to the experiment. Rabbits were anesthetized with isoflurane, and IV catheters were placed in a medial saphenous or jugular vein for collection of blood samples. One blood sample was collected before treatment with tramadol. Rabbits were allowed to recover from anesthesia a minimum of 1 hour before treatment. Then, tramadol (11 mg/kg, PO) was administered once, and blood samples were collected at various time points up to 360 minutes after administration. Blood samples were analyzed with high-performance liquid chromatography to determine plasma concentrations of tramadol and its major metabolite (O-desmethyltramadol).

Results—No adverse effects were detected after oral administration of tramadol to rabbits. Mean ± SD half-life of tramadol after administration was 145.4 ± 81.0 minutes; mean ± SD maximum plasma concentration was 135.3 ± 89.1 ng/mL.

Conclusions and Clinical Relevance—Although the dose of tramadol required to provide analgesia in rabbits is unknown, the dose administered in the study reported here did not reach a plasma concentration of tramadol or O-desmethyltramadol that would provide sufficient analgesia in humans for clinically acceptable periods. Many factors may influence absorption of orally administered tramadol in rabbits.

Contributor Notes

Supported by the American Rabbit Breeders Association, the University of Tennessee College of Veterinary Medicine Companion Animal Fund, and Carolyn Bond.

The authors thank Nancy Zagaya for technical assistance and Anik Vasington for assistance with graphics.

Address correspondence to Dr. Souza.