FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Toxicol Appl Pharmacol / Antinociceptive effects, metabolism and disposition of ketam...
Toxicology and applied pharmacology2006; 216(3); 373-386; doi: 10.1016/j.taap.2006.06.011

Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion.

Abstract: Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 microg/ml S-ketamine over 120 min under isoflurane anesthesia was performed in Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were determined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies. The peak-to-peak amplitude and the duration of the NWR decreased significantly during TCI and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R- and S-ketamine and R- and S-norketamine. Furthermore, biotransformation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TCI at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R- and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R- and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses).
Get Full Text
Publication Date: 2006-07-03 PubMed ID: 16919695PubMed Central: PMC2039908DOI: 10.1016/j.taap.2006.06.011Google 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.
LinkedInCopy
  • Journal Article
  • Research Support
  • N.I.H.
  • Intramural
  • Research Support
  • Non-U.S. Gov't

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 article focuses on investigating the effects of ketamine as an anesthetic in ponies. The study developed a pharmacokinetic model for monitoring ketamine use, studied its effect on pain reflexes, its metabolic process, and how it’s disseminated in the ponies’ bodies.

Study Design

  • The researchers developed a physiologically-based pharmacokinetic (PBPk) model for ketamine in ponies – a mathematical model that can predict the absorption, distribution, metabolism, and excretion of drugs in the body.
  • They conducted a target-controlled infusion (TCI) of ketamine under isoflurane anesthesia in Shetland ponies, aiming for a specific level of ketamine concentration within the plasma.
  • They aimed to understand the effect of low-dose ketamine on the nociceptive withdrawal reflex (NWR) – a protective reflex response where a body part is automatically removed from a harmful stimulus.
  • Throughout the TCI, an electromyographic assessment was performed to measure the NWR. This determines how the reflex changes in amplitude and duration during and after the anesthesia.

Findings

  • They noted a significant decrease in both the amplitude and the duration of the NWR during the TCI, which gradually returned to normal after TCI was complete.
  • The PBPk model successfully predicted plasma and tissue levels of R- and S-ketamine and R- and S-norketamine.
  • The study found that the liver and lungs carried out the first-pass metabolism (the initial metabolism that a drug undergoes in the liver and the gut wall after oral administration) of ketamine.
  • Plasma concentrations of S-norketamine (a metabolite of ketamine) were shown to be higher compared to R-norketamine at all time points during TCI.
  • The analysis suggested equal biotransformation rates from the parent compounds (ketamine) to the primary metabolites (R- and S-norketamine), but further transformation into additional metabolites showed variances.
  • The model developed in this study can provide predictions of R- and S-ketamine and norketamine concentrations in other clinical settings, like in horses, for instance.

Cite This Article

APA
Knobloch M, Portier CJ, Levionnois OL, Theurillat R, Thormann W, Spadavecchia C, Mevissen M. (2006). Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion. Toxicol Appl Pharmacol, 216(3), 373-386. https://doi.org/10.1016/j.taap.2006.06.011

Publication

Toxicology and applied pharmacology
ISSN: 0041-008X
NlmUniqueID: 0416575
Country: United States
Language: English
Volume: 216
Issue: 3
Pages: 373-386

Researcher Affiliations

Knobloch, M
  • Division Veterinary Pharmacology and Toxicology, University of Bern, 3012 Bern, Switzerland.
Portier, C J
    Levionnois, O L
      Theurillat, R
        Thormann, W
          Spadavecchia, C
            Mevissen, M

              MeSH Terms

              • Algorithms
              • Analgesics
              • Anesthesia
              • Anesthetics, Dissociative / administration & dosage
              • Anesthetics, Dissociative / pharmacology
              • Animals
              • Biotransformation
              • Drug Delivery Systems
              • Electrophysiology
              • Horses / physiology
              • Infusions, Intravenous
              • Ketamine / administration & dosage
              • Ketamine / analogs & derivatives
              • Ketamine / blood
              • Ketamine / pharmacokinetics
              • Ketamine / pharmacology
              • Male
              • Models, Statistical
              • Pain Measurement / drug effects
              • Reflex / drug effects
              • Stereoisomerism
              • Tissue Distribution

              Grant Funding

              • Wellcome Trust
              • Intramural NIH HHS
              • Z01 ES048002-18 / NIEHS NIH HHS

              References

              This article includes 69 references
              1. Arendt-Nielsen L, Petersen-Felix S. Wind-up and neuroplasticity: is there a correlation to clinical pain?. Eur J Anaesthesiol Suppl 1995 May;10:1-7.
                pubmed: 7641635
              2. Arendt-Nielsen L, Petersen-Felix S, Fischer M, Bak P, Bjerring P, Zbinden AM. The effect of N-methyl-D-aspartate antagonist (ketamine) on single and repeated nociceptive stimuli: a placebo-controlled experimental human study.. Anesth Analg 1995 Jul;81(1):63-8.
                pubmed: 7598284doi: 10.1097/00000539-199507000-00013google scholar: lookup
              3. Arendt-Nielsen L, Nielsen J, Petersen-Felix S, Schnider TW, Zbinden AM. Effect of racemic mixture and the (S+)-isomer of ketamine on temporal and spatial summation of pain.. Br J Anaesth 1996 Nov;77(5):625-31.
                pubmed: 8957979doi: 10.1093/bja/77.5.625google scholar: lookup
              4. Baggot JD. Drug distribution.. Principles of Drug Disposition in Domestic Animals: The Basis of Veterinary Clinical Pharmacology 1977;pp. 48–72.
              5. Barone R. Appareil digestif, glandes annexes de l'intestin, foie.. Anatomie comparée des mammifères domestiques; tome 3: Splanchnologie I 1984a;pp. 507–561.
              6. Barone R. Appareil respiratoire, poumons.. Anatomie comparée des mammifères domestiques; tome 3: Splanchnologie I 1984b;pp. 756–800.
              7. Barone R. Myologie, caractères généraux des muscles.. Anatomie comparée des mammifères domestiques; tome 2: Arthrologie et Myologie 1989;pp. 357–375.
              8. Barone R. Apparail uro-génital, reins.. Anatomie comparée des mammifères domestique; tome 4: Splanchnologie II 1990;pp. 19–45.
              9. Barone R. Cœur, caractères généraux et conformation extérieure.. Anatomie comparée des mammifères domestique: tome 5: Angiologie 1996;pp. 14–25.
              10. Berg R. Angewandte Anatomie der Schlachttierkörper.. Angewandte und topographische Anatomie der Haustiere 1995;pp. 475–495.
              11. Chang ML, Yang J, Kem S, Klaidman L, Sugawara T, Chan PH, Adams JD Jr. Nicotinamide and ketamine reduce infarct volume and DNA fragmentation in rats after brain ischemia and reperfusion.. Neurosci Lett 2002 Apr 12;322(3):137-40.
                pubmed: 11897157doi: 10.1016/s0304-3940(01)02520-4google scholar: lookup
              12. Cohen ML, Trevor AJ. On the cerebral accumulation of ketamine and the relationship between metabolism of the drug and its pharmacological effects.. J Pharmacol Exp Ther 1974 May;189(2):351-8.
                pubmed: 4829218
              13. Deavers S, Rosborough JP, Garner HE, Huggins RA, Amend JF. Blood volumes and total body water in the domestic pony.. J Appl Physiol 1973 Mar;34(3):341-3.
                pubmed: 4688124doi: 10.1152/jappl.1973.34.3.341google scholar: lookup
              14. Delatour P, Jaussaud P, Courtot D, Fau D. Enantioselective N-demethylation of ketamine in the horse.. J Vet Pharmacol Ther 1991 Jun;14(2):209-12.
                pubmed: 1920610doi: 10.1111/j.1365-2885.1991.tb00825.xgoogle scholar: lookup
              15. Edwards SR, Mather LE. Tissue uptake of ketamine and norketamine enantiomers in the rat: indirect evidence for extrahepatic metabolic inversion.. Life Sci 2001 Sep 14;69(17):2051-66.
                pubmed: 11589520doi: 10.1016/s0024-3205(01)01287-5google scholar: lookup
              16. Engelhardt W. Kreislauf.. Physiologie der Haustiere 2000;pp. 171–189.
              17. Geisslinger G, Hering W, Thomann P, Knoll R, Kamp HD, Brune K. Pharmacokinetics and pharmacodynamics of ketamine enantiomers in surgical patients using a stereoselective analytical method.. Br J Anaesth 1993 Jun;70(6):666-71.
                pubmed: 8329260doi: 10.1093/bja/70.6.666google scholar: lookup
              18. Guirimand F, Dupont X, Brasseur L, Chauvin M, Bouhassira D. The effects of ketamine on the temporal summation (wind-up) of the R(III) nociceptive flexion reflex and pain in humans.. Anesth Analg 2000 Feb;90(2):408-14.
                pubmed: 10648330doi: 10.1097/00000539-200002000-00031google scholar: lookup
              19. Haddad S, Poulin P, Krishnan K. Relative lipid content as the sole mechanistic determinant of the adipose tissue:blood partition coefficients of highly lipophilic organic chemicals.. Chemosphere 2000 Apr;40(8):839-43.
                pubmed: 10718576doi: 10.1016/s0045-6535(99)00279-9google scholar: lookup
              20. Hartell NA, Headley PM. Spinal effects of four injectable anaesthetics on nociceptive reflexes in rats: a comparison of electrophysiological and behavioural measurements.. Br J Pharmacol 1990 Nov;101(3):563-8.
                pmc: PMC1917747pubmed: 2076476doi: 10.1111/j.1476-5381.1990.tb14121.xgoogle scholar: lookup
              21. Headley PM, Parsons CG, West DC. The role of N-methylaspartate receptors in mediating responses of rat and cat spinal neurones to defined sensory stimuli.. J Physiol 1987 Apr;385:169-88.
                pmc: PMC1192343pubmed: 2821241doi: 10.1113/jphysiol.1987.sp016490google scholar: lookup
              22. Henthorn TK, Krejcie TC, Niemann CU, Enders-Klein C, Shanks CA, Avram MJ. Ketamine distribution described by a recirculatory pharmacokinetic model is not stereoselective.. Anesthesiology 1999 Dec;91(6):1733-43.
                pubmed: 10598617doi: 10.1097/00000542-199912000-00027google scholar: lookup
              23. Hijazi Y, Boulieu R. Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes.. Drug Metab Dispos 2002 Jul;30(7):853-8.
                pubmed: 12065445doi: 10.1124/dmd.30.7.853google scholar: lookup
              24. Hijazi Y, Bodonian C, Bolon M, Salord F, Boulieu R. Pharmacokinetics and haemodynamics of ketamine in intensive care patients with brain or spinal cord injury.. Br J Anaesth 2003 Feb;90(2):155-60.
                pubmed: 12538370doi: 10.1093/bja/aeg028google scholar: lookup
              25. Ihmsen H, Geisslinger G, Schüttler J. Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine.. Clin Pharmacol Ther 2001 Nov;70(5):431-8.
                pubmed: 11719729doi: 10.1067/mcp.2001.119722google scholar: lookup
              26. Jansen KL. A review of the nonmedical use of ketamine: use, users and consequences.. J Psychoactive Drugs 2000 Oct-Dec;32(4):419-33.
                pubmed: 11210204doi: 10.1080/02791072.2000.10400244google scholar: lookup
              27. Joubert K. Ketamine hydrochloride--an adjunct for analgesia in dogs with burn wounds.. J S Afr Vet Assoc 1998 Sep;69(3):95-7.
                pubmed: 9850513doi: 10.4102/jsava.v69i3.825google scholar: lookup
              28. Kharasch ED, Labroo R. Metabolism of ketamine stereoisomers by human liver microsomes.. Anesthesiology 1992 Dec;77(6):1201-7.
                pubmed: 1466470doi: 10.1097/00000542-199212000-00022google scholar: lookup
              29. Klepstad P, Maurset A, Moberg ER, Oye I. Evidence of a role for NMDA receptors in pain perception.. Eur J Pharmacol 1990 Oct 23;187(3):513-8.
                pubmed: 1963598doi: 10.1016/0014-2999(90)90379-kgoogle scholar: lookup
              30. Kohn MC, Melnick RL. Effects of the structure of a toxicokinetic model of butadiene inhalation exposure on computed production of carcinogenic intermediates.. Toxicology 1996 Oct 28;113(1-3):31-9.
                pubmed: 8901880doi: 10.1016/0300-483x(96)03424-5google scholar: lookup
              31. Kohrs R, Durieux ME. Ketamine: teaching an old drug new tricks.. Anesth Analg 1998 Nov;87(5):1186-93.
                pubmed: 9806706doi: 10.1097/00000539-199811000-00039google scholar: lookup
              32. Koo JW, Parham F, Kohn MC, Masten SA, Brock JW, Needham LL, Portier CJ. The association between biomarker-based exposure estimates for phthalates and demographic factors in a human reference population.. Environ Health Perspect 2002 Apr;110(4):405-10.
                pmc: PMC1240804pubmed: 11940459doi: 10.1289/ehp.02110405google scholar: lookup
              33. Larsson P, Persson E, Tydén E, Tjälve H. Cell-specific activation of aflatoxin B1 correlates with presence of some cytochrome P450 enzymes in olfactory and respiratory tissues in horse.. Res Vet Sci 2003 Jun;74(3):227-33.
                pubmed: 12726741doi: 10.1016/s0034-5288(02)00191-1google scholar: lookup
              34. Laulin JP, Maurette P, Corcuff JB, Rivat C, Chauvin M, Simonnet G. The role of ketamine in preventing fentanyl-induced hyperalgesia and subsequent acute morphine tolerance.. Anesth Analg 2002 May;94(5):1263-9, table of contents.
                pubmed: 11973202doi: 10.1097/00000539-200205000-00040google scholar: lookup
              35. Löscher W, Ganter M, Fassbender CP. Correlation between drug and metabolite concentrations in plasma and anesthetic action of ketamine in swine.. Am J Vet Res 1990 Mar;51(3):391-8.
                pubmed: 2316916
              36. Lutz RJ, Dedrick RL, Zaharko DS. Physiological pharmacokinetics: an in vivo approach to membrane transport.. Pharmacol Ther 1980;11(3):559-92.
                pubmed: 7003607doi: 10.1016/0163-7258(80)90042-xgoogle scholar: lookup
              37. Maitre PO, Shafer SL. A simple pocket calculator approach to predict anesthetic drug concentrations from pharmacokinetic data.. Anesthesiology 1990 Aug;73(2):332-6.
                pubmed: 2382854doi: 10.1097/00000542-199008000-00022google scholar: lookup
              38. Manohar M, Gustafson R, Goetz TE, Nganwa D. Systemic distribution of blood flow in ponies during 1.45%, 1.96%, and 2.39% end-tidal isoflurane-O2 anesthesia.. Am J Vet Res 1987 Oct;48(10):1504-10.
                pubmed: 3674561
              39. McConaghy FF, Hodgson DR, Rose RJ, Hales JR. Redistribution of cardiac output in response to heat exposure in the pony.. Equine Vet J Suppl 1996 Jul;(22):42-6.
                pubmed: 8894549doi: 10.1111/j.2042-3306.1996.tb05030.xgoogle scholar: lookup
              40. MENDELL LM, WALL PD. RESPONSES OF SINGLE DORSAL CORD CELLS TO PERIPHERAL CUTANEOUS UNMYELINATED FIBRES.. Nature 1965 Apr 3;206:97-9.
                pubmed: 14334366doi: 10.1038/206097a0google scholar: lookup
              41. Menigaux C, Guignard B, Fletcher D, Sessler DI, Dupont X, Chauvin M. Intraoperative small-dose ketamine enhances analgesia after outpatient knee arthroscopy.. Anesth Analg 2001 Sep;93(3):606-12.
                pubmed: 11524327doi: 10.1097/00000539-200109000-00016google scholar: lookup
              42. Muir WW 3rd, Sams R. Effects of ketamine infusion on halothane minimal alveolar concentration in horses.. Am J Vet Res 1992 Oct;53(10):1802-6.
                pubmed: 1456524
              43. Nickel R, Schummer A, Seiferle E. Lunge.. Lehrbuch der Anatomie der Haustiere; Band II: Eingeweide 1995;pp. 255–265.
              44. Oye I, Paulsen O, Maurset A. Effects of ketamine on sensory perception: evidence for a role of N-methyl-D-aspartate receptors.. J Pharmacol Exp Ther 1992 Mar;260(3):1209-13.
                pubmed: 1312163
              45. Parks CM, Manohar M. Distribution of blood flow during moderate and strenuous exercise in ponies (Equus caballus).. Am J Vet Res 1983 Oct;44(10):1861-6.
                pubmed: 6416115
              46. Pedraz JL, Lanao JM, Hernandez JM, Domínguez-Gil A. The biotransformation kinetics of ketamine "in vitro" in rabbit liver and lung microsome fractions.. Eur J Drug Metab Pharmacokinet 1986 Jan-Mar;11(1):9-16.
                pubmed: 3720798doi: 10.1007/bf03189769google scholar: lookup
              47. Persson J, Hasselström J, Maurset A, Oye I, Svensson JO, Almqvist O, Scheinin H, Gustafsson LL, Almqvist O. Pharmacokinetics and non-analgesic effects of S- and R-ketamines in healthy volunteers with normal and reduced metabolic capacity.. Eur J Clin Pharmacol 2002 Feb;57(12):869-75.
                pubmed: 11936706doi: 10.1007/s002280100353google scholar: lookup
              48. Poulin P, Krishnan K. A tissue composition-based algorithm for predicting tissue:air partition coefficients of organic chemicals.. Toxicol Appl Pharmacol 1996 Jan;136(1):126-30.
                pubmed: 8560465doi: 10.1006/taap.1996.0015google scholar: lookup
              49. Price DD, Mao J, Frenk H, Mayer DJ. The N-methyl-D-aspartate receptor antagonist dextromethorphan selectively reduces temporal summation of second pain in man.. Pain 1994 Nov;59(2):165-174.
                pubmed: 7892014doi: 10.1016/0304-3959(94)90069-8google scholar: lookup
              50. Reddy MB, Andersen ME, Morrow PE, Dobrev ID, Varaprath S, Plotzke KP, Utell MJ. Physiological modeling of inhalation kinetics of octamethylcyclotetrasiloxane in humans during rest and exercise.. Toxicol Sci 2003 Mar;72(1):3-18.
                pubmed: 12604830doi: 10.1093/toxsci/kfg001google scholar: lookup
              51. Scallet AC, Schmued LC, Slikker W Jr, Grunberg N, Faustino PJ, Davis H, Lester D, Pine PS, Sistare F, Hanig JP. Developmental neurotoxicity of ketamine: morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons.. Toxicol Sci 2004 Oct;81(2):364-70.
                pubmed: 15254342doi: 10.1093/toxsci/kfh224google scholar: lookup
              52. Schwieger IM, Szlam F, Hug CC Jr. The pharmacokinetics and pharmacodynamics of ketamine in dogs anesthetized with enflurane.. J Pharmacokinet Biopharm 1991 Apr;19(2):145-56.
                pubmed: 2013837doi: 10.1007/bf01073866google scholar: lookup
              53. Spadavecchia C, Spadavecchia L, Andersen OK, Arendt-Nielsen L, Leandri M, Schatzmann U. Quantitative assessment of nociception in horses by use of the nociceptive withdrawal reflex evoked by transcutaneous electrical stimulation.. Am J Vet Res 2002 Nov;63(11):1551-6.
                pubmed: 12428666doi: 10.2460/ajvr.2002.63.1551google scholar: lookup
              54. Spadavecchia C, Andersen OK, Arendt-Nielsen L, Spadavecchia L, Doherr M, Schatzmann U. Investigation of the facilitation of the nociceptive withdrawal reflex evoked by repeated transcutaneous electrical stimulations as a measure of temporal summation in conscious horses.. Am J Vet Res 2004 Jul;65(7):901-8.
                pubmed: 15281647doi: 10.2460/ajvr.2004.65.901google scholar: lookup
              55. Spadavecchia C, Levionnois O, Kronen PW, Leandri M, Spadavecchia L, Schatzmann U. Peri-MAC isoflurane depression of a nociceptive withdrawal reflex evoked by transcutaneous electrical stimulation in ponies.. Am. J. Vet. Res. 2005;66:1992–1998.
                pubmed: 0
              56. Theurillat R, Knobloch M, Levionnois O, Larenza P, Mevissen M, Thormann W. Characterization of the stereoselective biotransformation of ketamine to norketamine via determination of their enantiomers in equine plasma by capillary electrophoresis.. Electrophoresis 2005 Oct;26(20):3942-51.
                pubmed: 16167314doi: 10.1002/elps.200500059google scholar: lookup
              57. Trevor AJ, Woolf TF, Baillie TA, Adams JD, Castagnoli N. Stereoselective metabolism of ketamine enantiomers, phencyclidine and related arylcyclohexamines: present and future applications.. NPP Books 1983;pp. 279–289.
              58. Wagner AE, Walton JA, Hellyer PW, Gaynor JS, Mama KR. Use of low doses of ketamine administered by constant rate infusion as an adjunct for postoperative analgesia in dogs.. J Am Vet Med Assoc 2002 Jul 1;221(1):72-5.
                pubmed: 12420827doi: 10.2460/javma.2002.221.72google scholar: lookup
              59. Waterman AE. Influence of premedication with xylazine on the distribution and metabolism of intramuscularly administered ketamine in cats.. Res Vet Sci 1983 Nov;35(3):285-90.
                pubmed: 6665311
              60. Waterman AE, Robertson SA, Lane JG. Pharmacokinetics of intravenously administered ketamine in the horse.. Res Vet Sci 1987 Mar;42(2):162-6.
                pubmed: 3589163
              61. Werner C, Reeker W, Engelhard K, Lu H, Kochs E. [Ketamine racemate and S-(+)-ketamine. Cerebrovascular effects and neuroprotection following focal ischemia].. Anaesthesist 1997 Mar;46 Suppl 1:S55-60.
                pubmed: 9163280doi: 10.1007/pl00002466google scholar: lookup
              62. White PF, Pudwill CR, Johnston RR, Way WL, Trevor AJ, Marietta MP. Effects of halothane anesthesia on ketamine biotransformation.. Proc West Pharmacol Soc 1976;19:227-31.
                pubmed: 995991
              63. White PF, Way WL, Trevor AJ. Ketamine--its pharmacology and therapeutic uses.. Anesthesiology 1982 Feb;56(2):119-36.
                pubmed: 6892475doi: 10.1097/00000542-198202000-00007google scholar: lookup
              64. White PF, Schüttler J, Shafer A, Stanski DR, Horai Y, Trevor AJ. Comparative pharmacology of the ketamine isomers. Studies in volunteers.. Br J Anaesth 1985 Feb;57(2):197-203.
                pubmed: 3970799doi: 10.1093/bja/57.2.197google scholar: lookup
              65. Williams ML, Wainer IW. Role of chiral chromatography in therapeutic drug monitoring and in clinical and forensic toxicology.. Ther Drug Monit 2002 Apr;24(2):290-6.
                pubmed: 11897974doi: 10.1097/00007691-200204000-00010google scholar: lookup
              66. Woolf CJ, Thompson SWN. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states.. Pain 1991 Mar;44(3):293-299.
                pubmed: 1828878doi: 10.1016/0304-3959(91)90100-cgoogle scholar: lookup
              67. Wright M. Pharmacologic effects of ketamine and its use in veterinary medicine.. J Am Vet Med Assoc 1982 Jun 15;180(12):1462-71.
                pubmed: 6124527
              68. Yanagihara Y, Kariya S, Ohtani M, Uchino K, Aoyama T, Yamamura Y, Iga T. Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes.. Drug Metab Dispos 2001 Jun;29(6):887-90.
                pubmed: 11353758
              69. Zielmann S, Kazmaier S, Schnüll S, Weyland A. [S-(+)-Ketamine and circulation].. Anaesthesist 1997 Mar;46 Suppl 1:S43-6.
                pubmed: 9163278doi: 10.1007/pl00002464google scholar: lookup

              Citations

              This article has been cited 7 times.
              1. Sandbaumhüter FA, Aerts JT, Theurillat R, Andrén PE, Thormann W, Jansson ET. Enantioselective CE-MS analysis of ketamine metabolites in urine.. Electrophoresis 2023 Jan;44(1-2):125-134.
                doi: 10.1002/elps.202200175pubmed: 36398998google scholar: lookup
              2. Troya-Portillo L, López-Sanromán J, Villalba-Orero M, Santiago-Llorente I. Cardiorespiratory, Sedative and Antinociceptive Effects of a Medetomidine Constant Rate Infusion with Morphine, Ketamine or Both.. Animals (Basel) 2021 Jul 13;11(7).
                doi: 10.3390/ani11072081pubmed: 34359209google scholar: lookup
              3. Mathews KA. Emergency and Critical Care Medicine: An Essential Component of All Specialties and Practices.. Front Vet Sci 2017;4:165.
                doi: 10.3389/fvets.2017.00165pubmed: 29075634google scholar: lookup
              4. Giroux MC, Santamaria R, Hélie P, Burns P, Beaudry F, Vachon P. Physiological, pharmacokinetic and liver metabolism comparisons between 3-, 6-, 12- and 18-month-old male Sprague Dawley rats under ketamine-xylazine anesthesia.. Exp Anim 2016;65(1):63-75.
                doi: 10.1538/expanim.15-0039pubmed: 26489361google scholar: lookup
              5. Elfenbein JR, Robertson SA, MacKay RJ, KuKanich B, Sanchez L. Systemic and anti-nociceptive effects of prolonged lidocaine, ketamine, and butorphanol infusions alone and in combination in healthy horses.. BMC Vet Res 2014;10 Suppl 1(Suppl 1):S6.
                doi: 10.1186/1746-6148-10-S1-S6pubmed: 25238633google scholar: lookup
              6. Moaddel R, Venkata SL, Tanga MJ, Bupp JE, Green CE, Iyer L, Furimsky A, Goldberg ME, Torjman MC, Wainer IW. A parallel chiral-achiral liquid chromatographic method for the determination of the stereoisomers of ketamine and ketamine metabolites in the plasma and urine of patients with complex regional pain syndrome.. Talanta 2010 Oct 15;82(5):1892-904.
                doi: 10.1016/j.talanta.2010.08.005pubmed: 20875593google scholar: lookup
              7. Schmitz A, Portier CJ, Thormann W, Theurillat R, Mevissen M. Stereoselective biotransformation of ketamine in equine liver and lung microsomes.. J Vet Pharmacol Ther 2008 Oct;31(5):446-55.
                doi: 10.1111/j.1365-2885.2008.00972.xpubmed: 19000264google scholar: lookup
              Subscribe to our newsletter
              Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.