Pharmacokinetics, intraoperative effect and postoperative analgesia of tramadol in cats.

Tramadol is a synthetic codeine analogue used as an analgesic in human and veterinary medicine, but not approved for use in cats. Tramadol (2 mg/kg) was administered intravenously (IV) as preoperative analgesic in 12 cats (6 males) undergoing surgical gonadectomy. The pharmacokinetic profile of the drug and its O-desmethyl metabolite were determined in 8 animals (4 males), while intraoperative effects and postoperative analgesia, estimated by subjective pain score (0-24), were evaluated in all. Mean intraoperative isoflurane consumption was reduced, but hypoventilation was not observed. Sex-related differences were not observed, particularly in terms of postoperative analgesia: rescue analgesic was never administered. Concentrations of the active O-desmethyl metabolite were persistently high in all the animals. Considering the results obtained in this study, tramadol, at the dose of 2 mg/kg IV, did not produce any evident intraoperative cardiorespiratory side effects and with additional investigation may prove to be an appropriate intraoperative analgesic in cats undergoing gonadectomy.

[1]  J. Besson,et al.  Evidence for a noradrenergic component in the antinociceptive effect of the analgesic agent tramadol in an animal model of clinical pain, the arthritic rat. , 1992, European journal of pharmacology.

[2]  C. Gillen,et al.  Affinity, potency and efficacy of tramadol and its metabolites at the cloned human µ-opioid receptor , 2000, Naunyn-Schmiedeberg's Archives of Pharmacology.

[3]  C T Hung,et al.  Estimation of variance for harmonic mean half-lives. , 1985, Journal of pharmaceutical sciences.

[4]  E. Welsh,et al.  Comparison of three methods used for assessment of pain in dogs. , 1998, Journal of the American Veterinary Medical Association.

[5]  A. Waterman,et al.  Analgesia in cats , 1997, In Practice.

[6]  M. Chenoweth Inhalation anesthetics. , 1978, Federation proceedings.

[7]  Lesley J. Smith,et al.  Systemic lidocaine infusion as an analgesic for intraocular surgery in dogs: a pilot study. , 2004, Veterinary anaesthesia and analgesia.

[8]  B. Wilffert,et al.  Influence of tramadol on neurotransmitter systems of the rat brain. , 1996, Arzneimittel-Forschung.

[9]  S. Robertson Managing pain in feline patients. , 2005, The Veterinary clinics of North America. Small animal practice.

[10]  A. Shih,et al.  Comparison between the analgesic effects of morphine and tramadol delivered epidurally in cats receiving a standardized noxious stimulation , 2009, Journal of feline medicine and surgery.

[11]  M. Uyar,et al.  Analysis of the antinociceptive effect of systemic administration of tramadol and dexmedetomidine combination on rat models of acute and neuropathic pain , 2007, Pharmacology Biochemistry and Behavior.

[12]  R. Houmes,et al.  Efficacy and Safety of Tramadol Versus Morphine for Moderate and Severe Postoperative Pain With Special Regard to Respiratory Depression , 1992, Anesthesia and analgesia.

[13]  D. Mayer Analgesia produced by electrical stimulation of the brain , 1984, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[14]  C. Padovani,et al.  Analgesic efficacy of perioperative use of vedaprofen, tramadol or their combination in cats undergoing ovariohysterectomy⋆ , 2009, Journal of feline medicine and surgery.

[15]  G. Blaschke,et al.  Direct determination of tramadol glucuronides in human urine by high-performance liquid chromatography with fluorescence detection. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[16]  R. Odore,et al.  Mepartricin long-term administration regulates steroid hormone and adrenergic receptor concentrations in the prostate of aged rats. , 2006, Journal of veterinary pharmacology and therapeutics.

[17]  J. Flório,et al.  Pharmacokinetics of tramadol and o-desmethyltramadol in goats after intravenous and oral administration. , 2007, Journal of veterinary pharmacology and therapeutics.

[18]  D. Tibboel,et al.  Contribution of glucuronidation to tramadol disposition in early neonatal life. , 2006, Basic & clinical pharmacology & toxicology.

[19]  P. Cagnardi,et al.  Pharmacokinetics of tramadol in cats undergoing neutering , 2006 .

[20]  L. Lindgren,et al.  Comparison of respiratory effects of tramadol and oxycodone. , 1997, Journal of clinical anesthesia.

[21]  F. Caloni,et al.  Serum protein binding of some sulphonamides, quinolones and fluoroquinolones in farm and domestic animals , 1997 .

[22]  D. Fantoni,et al.  A comparison of preoperative tramadol and morphine for the control of early postoperative pain in canine ovariohysterectomy. , 2003, Veterinary anaesthesia and analgesia.

[23]  B. Pypendop,et al.  Pharmacokinetics of tramadol, and its metabolite O-desmethyl-tramadol, in cats. , 2007, Journal of veterinary pharmacology and therapeutics.

[24]  C. Natalini,et al.  Evaluation of the analgesic effects of epidurally administered morphine, alfentanil, butorphanol, tramadol, and U50488H in horses. , 2000, American journal of veterinary research.

[25]  K. Lehmann,et al.  Postoperative Patient‐Controlled Analgesia with Tramadol: Analgesic Efficacy and Minimum Effective Concentrations , 1990 .

[26]  M. Conzemius,et al.  Correlation between subjective and objective measures used to determine severity of postoperative pain in dogs. , 1997, Journal of the American Veterinary Medical Association.

[27]  J. Schneider,et al.  Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids. , 1988, Arzneimittel-Forschung.

[28]  J. Ilkiw Veterinary Anaesthesia and Analgesia: Editorial , 2004 .

[29]  M. Payton,et al.  Effect of orally administered tramadol alone or with an intravenously administered opioid on minimum alveolar concentration of sevoflurane in cats. , 2008, Journal of the American Veterinary Medical Association.

[30]  P. Taylor,et al.  Antinociceptive effects of tramadol and acepromazine in cats , 2008, Journal of feline medicine and surgery.

[31]  P. Wouters,et al.  Effects of tramadol on minimum alveolar concentration (MAC) of isoflurane in rats. , 1999, British journal of anaesthesia.

[32]  L. Lindgren,et al.  Comparison of respiratory effects of tramadol and pethidine. , 1998, European journal of anaesthesiology.

[33]  C. Padovani,et al.  Perioperative administration of vedaprofen, tramadol or their combination does not interfere with platelet aggregation, bleeding time and biochemical variables in cats⋆ , 2009, Journal of feline medicine and surgery.

[34]  M. Shimoda,et al.  Characterization of cytochrome P450-mediated drug metabolism in cats. , 2007, Journal of veterinary pharmacology and therapeutics.

[35]  B. Kukanich,et al.  Pharmacokinetics of tramadol and the metabolite O-desmethyltramadol in dogs. , 2004, Journal of veterinary pharmacology and therapeutics.

[36]  B. Pypendop,et al.  Effects of tramadol hydrochloride on the thermal threshold in cats. , 2009, American journal of veterinary research.

[37]  P. Kamerman,et al.  Postoperative Administration of the Analgesic Tramadol, but Not the Selective Cyclooxygenase-2 Inhibitor Parecoxib, Abolishes Postoperative Hyperalgesia in a New Model of Postoperative Pain in Rats , 2007, Pharmacology.

[38]  L. Arendt-Nielsen,et al.  The hypoalgesic effect of tramadol in relation to CYP2D6 * , 1996, Clinical pharmacology and therapeutics.

[39]  P. Cagnardi,et al.  Pharmacokinetics and efficacy of intravenous and extradural tramadol in dogs. , 2010, Veterinary journal.

[40]  S. Grond,et al.  Clinical Pharmacology of Tramadol , 2004, Clinical pharmacokinetics.

[41]  M. Vickers,et al.  Tramadol: pain relief by an opioid without depression of respiration , 1992, Anaesthesia.

[42]  M. Giorgi,et al.  Pharmacokinetics of Tramadol and its Metabolites M1, M2 and M5 in Horses Following Intravenous, Immediate Release (Fasted/Fed) and Sustained Release Single Dose Administration , 2007 .

[43]  C. Perry,et al.  Tramadol , 2000, Drugs.

[44]  Kiyoshi Yamaoka,et al.  Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations , 1978, Journal of Pharmacokinetics and Biopharmaceutics.

[45]  R. Shank,et al.  Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an 'atypical' opioid analgesic. , 1992, The Journal of pharmacology and experimental therapeutics.

[46]  N. Chauret,et al.  In vitro comparison of cytochrome P450-mediated metabolic activities in human, dog, cat, and horse. , 1997, Drug metabolism and disposition: the biological fate of chemicals.

[47]  M. Britzi,et al.  Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration. , 2007, Journal of veterinary pharmacology and therapeutics.

[48]  P. Cagnardi,et al.  Bioavailability of tramadol after epidural administration in dog , 2006 .

[49]  A M Firth,et al.  Development of a scale to evaluate postoperative pain in dogs. , 1999, Journal of the American Veterinary Medical Association.

[50]  A. Nolan,et al.  Development of the short-form Glasgow Composite Measure Pain Scale (CMPS-SF) and derivation of an analgesic intervention score , 2007, Animal Welfare.

[51]  H. Boothe,et al.  Comparison of three methods for relief of pain after ear canal ablation in dogs. , 1996, Veterinary surgery : VS.