{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:48:49Z","timestamp":1790210929057,"version":"4.1.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Vet Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The present study aimed to collect pharmacokinetic data of a methadone continuous rate infusion (CRI) and to investigate its effect on mechanical and thermal nociceptive thresholds. Seven, 47 to 54\u2009months old beagle dogs, weighing 9.8 to 21.2\u2009kg, were used in this experimental, randomized, blinded, placebo-controlled crossover study. Each dog was treated twice with either a methadone bolus of 0.2\u2009mg\u2009kg<jats:sup>\u2212\u20091<\/jats:sup>followed by a 0.1\u2009mg\u2009kg<jats:sup>\u2212\u20091<\/jats:sup>\u2009h<jats:sup>\u2212\u20091<\/jats:sup>methadone CRI (group M) or an equivalent volume of isotonic saline solution (group P) for 72\u2009h. Mechanical and thermal thresholds, as well as vital parameters and sedation were measured during CRI and for further 24\u2009h. Blood samples for methadone plasma concentrations were collected during this 96\u2009h period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Percentage thermal excursion (%TE) increased significantly from baseline (BL) until 3\u2009h after discontinuation of CRI in M. Within P and between treatment groups differences were not significant. Mechanical threshold (MT) increased in M until 2\u2009h after CRI discontinuation. Bradycardia and hypothermia occurred in M during drug administration and dogs were mildly sedated for the first 47\u2009h. Decreased food intake and regurgitation were observed in M in five and four dogs, respectively. For methadone a volume of distribution of 10.26\u2009l\u2009kg<jats:sup>\u2212\u20091<\/jats:sup>and a terminal half-life of 2.4\u2009h were detected and a clearance of 51.44\u2009ml\u2009kg<jats:sup>\u2212\u20091<\/jats:sup>\u2009min<jats:sup>\u2212\u20091<\/jats:sup>was calculated. Effective methadone plasma concentrations for thermal and mechanical antinociception were above 17\u2009ng\u2009ml<jats:sup>\u2212\u20091<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A methadone CRI of 0.1\u2009mg\u2009kg<jats:sup>\u2212\u20091<\/jats:sup>\u2009h<jats:sup>\u2212\u20091<\/jats:sup>for 3\u2009days after a loading dose results in steady anti-nociceptive effects in an acute pain model in healthy dogs. Main side effects were related to gastrointestinal tract, hypothermia, bradycardia and sedation.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12917-020-02735-3","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T18:02:40Z","timestamp":1610992960000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs"],"prefix":"10.1186","volume":"17","author":[{"given":"T.","family":"Amon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. B. R.","family":"K\u00e4stner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kietzmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"T\u00fcnsmeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,18]]},"reference":[{"issue":"3","key":"2735_CR1","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1111\/j.1467-2987.2004.00148.x","volume":"31","author":"CR Bley","year":"2004","unstructured":"Bley CR, Neiger-Aeschbacher G, Busato A, Schatzmann U. Comparison of perioperative racemic methadone, levo-methadone and dextromoramide in cats using indicators of post-operative pain. Vet Anaesth Analg. 2004;31(3):175\u201382.","journal-title":"Vet Anaesth Analg"},{"issue":"1","key":"2735_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12917-014-0194-7","volume":"10","author":"LB Cardozo","year":"2014","unstructured":"Cardozo LB, Cotes LC, Kahvegian MA, Rizzo MFC, Otsuki DA, Ferrigno CR, et al. Evaluation of the effects of methadone and tramadol on postoperative analgesia and serum interleukin-6 in dogs undergoing orthopaedic surgery. BMC Vet Res. 2014;10(1):1\u20137.","journal-title":"BMC Vet Res"},{"issue":"9","key":"2735_CR3","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1111\/jsap.12859","volume":"59","author":"M Shah","year":"2018","unstructured":"Shah M, Yates D, Hunt J, Murrell J. A comparison between methadone and buprenorphine for perioperative analgesia in dogs undergoing ovariohysterectomy. J Small Anim Pract. 2018;59(9):539\u201346.","journal-title":"J Small Anim Pract"},{"issue":"1","key":"2735_CR4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/S0304-3940(97)13391-2","volume":"223","author":"AL Gorman","year":"1997","unstructured":"Gorman AL, Elliott KJ, Inturrisi CE. The d- and l-isomers of methadone bind to the non-competitive site on the N-methyl-D-aspartate (NMDA) receptor in rat forebrain and spinal cord. Neurosci Lett. 1997;223(1):5\u20138.","journal-title":"Neurosci Lett"},{"issue":"3","key":"2735_CR5","first-page":"1263","volume":"274","author":"EE Codd","year":"1995","unstructured":"Codd EE, Shank RP, Schupsky JJ, Raffa RB. Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics - structural determinants and role in antinociception. J Pharmacol Exp Ther. 1995;274(3):1263\u201370.","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"2735_CR6","first-page":"366","volume":"299","author":"YX Xiao","year":"2001","unstructured":"Xiao YX, Smith RD, Caruso FS, Kellar KJ. Blockade of rat alpha 3 beta 4 nicotinic receptor function by methadone, its metabolites, and structural analogs. J Pharmacol Exp Ther. 2001;299(1):366\u201371.","journal-title":"J Pharmacol Exp Ther"},{"issue":"7","key":"2735_CR7","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1191\/0269216303pm815oa","volume":"17","author":"JS Morley","year":"2003","unstructured":"Morley JS, Bridson J, Nash TP, Miles JB, White S, Makin MK. Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial. Palliat Med. 2003;17(7):576\u201387.","journal-title":"Palliat Med"},{"issue":"3","key":"2735_CR8","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1017\/S0317167100004236","volume":"32","author":"D Moulin","year":"2005","unstructured":"Moulin D, Palma D, Watling C, Schulz V. Methadone in the management of intractable neuropathic noncancer pain. Can J Neurol Sci. 2005;32(3):340\u20133.","journal-title":"Can J Neurol Sci"},{"issue":"2","key":"2735_CR9","first-page":"1048","volume":"289","author":"AM Davis","year":"1999","unstructured":"Davis AM, Inturrisi CE. D-methadone blocks morphine tolerance and N-methyl-D-aspartate-induced hyperalgesia. J Pharmacol Exp Ther. 1999;289(2):1048\u201353.","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"2735_CR10","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1007\/BF03006849","volume":"27","author":"TH Stanley","year":"1980","unstructured":"Stanley TH, Liu WS, Webster LR, Johansen RK. Haemodynamic effects of intravenous methadone anaesthesia in dogs. Can Anaesth Soc J. 1980;27(1):52\u20137.","journal-title":"Can Anaesth Soc J"},{"issue":"3","key":"2735_CR11","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.tvjl.2012.03.019","volume":"194","author":"NA Garofalo","year":"2012","unstructured":"Garofalo NA, Teixeira Neto FJ, Pereira CD, Pignaton W, Vicente F, Alvaides RK. Cardiorespiratory and neuroendocrine changes induced by methadone in conscious and in isoflurane anaesthetised dogs. Vet J. 2012;194(3):398\u2013404.","journal-title":"Vet J"},{"issue":"4","key":"2735_CR12","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1111\/j.1365-2885.2008.01042.x","volume":"32","author":"AA Maiante","year":"2009","unstructured":"Maiante AA, Neto FJT, Beier SL, Corrente JE, Pedroso CEBP. Comparison of the cardio-respiratory effects of methadone and morphine in conscious dogs. J Vet Pharmacol Ther. 2009;32(4):317\u201328.","journal-title":"J Vet Pharmacol Ther"},{"issue":"6","key":"2735_CR13","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1111\/j.1467-2995.2008.00412.x","volume":"35","author":"ER Monteiro","year":"2008","unstructured":"Monteiro ER, Figueroa CD, Choma JC, Campagnol D, Bettini CM. Effects of methadone, alone or in combination with acepromazine or xylazine, on sedation and physiologic values in dogs. Vet Anaesth Analg. 2008;35(6):519\u201327.","journal-title":"Vet Anaesth Analg"},{"issue":"5","key":"2735_CR14","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1111\/j.1467-2995.2012.00757.x","volume":"39","author":"J Tunsmeyer","year":"2012","unstructured":"Tunsmeyer J, Vaske B, Bosing B, Kastner SB. Cardiovascular effects of a proprietary l-methadone\/fenpipramide combination (Polamivet) alone and in addition to acepromazine in healthy Beagle dogs. Vet Anaesth Analg. 2012;39(5):451\u201363.","journal-title":"Vet Anaesth Analg"},{"issue":"1","key":"2735_CR15","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/vaa.12086","volume":"41","author":"TM Menegheti","year":"2014","unstructured":"Menegheti TM, Wagatsuma JT, Pacheco AD, Perez B, Pacheco CM, Abimussi CJ, et al. Electrocardiographic evaluation and degree of sedation with three doses of methadone in healthy dogs [corrected]. Vet Anaesth Analg. 2014;41(1):97\u2013104.","journal-title":"Vet Anaesth Analg"},{"issue":"6","key":"2735_CR16","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/j.cvsm.2008.06.006","volume":"38","author":"DH Dyson","year":"2008","unstructured":"Dyson DH. Perioperative pain management in veterinary patients. Vet Clin North Am Small Anim Pract. 2008;38(6):1309\u201327.","journal-title":"Vet Clin North Am Small Anim Pract"},{"issue":"2","key":"2735_CR17","doi-asserted-by":"publisher","first-page":"183","DOI":"10.2460\/ajvr.2001.62.183","volume":"62","author":"DC Sellon","year":"2001","unstructured":"Sellon DC, Monroe VL, Roberts MC, Papich MG. Pharmacokinetics and adverse effects of butorphanol administered by single intravenous injection or continuous intravenous infusion in horses. Am J Vet Res. 2001;62(2):183\u20139.","journal-title":"Am J Vet Res"},{"key":"2735_CR18","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/1746-6148-8-206","volume":"8","author":"MV Hoffmann","year":"2012","unstructured":"Hoffmann MV, Kastner SB, Kietzmann M, Kramer S. Contact heat thermal threshold testing in beagle dogs: baseline reproducibility and the effect of acepromazine, levomethadone and fenpipramide. BMC Vet Res. 2012;8:206.","journal-title":"BMC Vet Res"},{"issue":"1","key":"2735_CR19","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1111\/j.1467-2995.2009.00476.x","volume":"37","author":"C Ingvast-Larsson","year":"2010","unstructured":"Ingvast-Larsson C, Holgersson A, Bondesson U, Lagerstedt AS, Olsson K. Clinical pharmacology of methadone in dogs. Vet Anaesth Analg. 2010;37(1):48\u201356.","journal-title":"Vet Anaesth Analg"},{"issue":"2","key":"2735_CR20","doi-asserted-by":"publisher","first-page":"Pl45","DOI":"10.1016\/0024-3205(94)00937-6","volume":"56","author":"K Kristensen","year":"1995","unstructured":"Kristensen K, Christensen CB, Christrup LL. The Mu(1), Mu(2), Delta, Kappa-Opioid receptor-binding profiles of methadone stereoisomers and morphine. Life Sci. 1995;56(2):Pl45\u201350.","journal-title":"Life Sci"},{"key":"2735_CR21","unstructured":"Noll M. Vergleich von Methadon und Levomethadon bez\u00fcglich ihrer Effekte auf die Minimale Alveol\u00e4re Konzentration (MAC) von Sevofluran sowie deren kutaner, thermischer und mechanischer Anti-Nozizeption beim Beagle. Hannover: Tier\u00e4rztliche Hochschule Hannover; 2018."},{"issue":"15","key":"2735_CR22","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1136\/vr.153.15.462","volume":"153","author":"SA Robertson","year":"2003","unstructured":"Robertson SA, Taylor PM, Lascelles BD, Dixon MJ. Changes in thermal threshold response in eight cats after administration of buprenorphine, butorphanol and morphine. Vet Rec. 2003;153(15):462\u20135.","journal-title":"Vet Rec"},{"issue":"6","key":"2735_CR23","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1111\/j.1365-2885.2006.00800.x","volume":"29","author":"PV Steagall","year":"2006","unstructured":"Steagall PV, Carnicelli P, Taylor PM, Luna SP, Dixon M, Ferreira TH. Effects of subcutaneous methadone, morphine, buprenorphine or saline on thermal and pressure thresholds in cats. J Vet Pharmacol Ther. 2006;29(6):531\u20137.","journal-title":"J Vet Pharmacol Ther"},{"issue":"5","key":"2735_CR24","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1111\/j.1467-2995.2006.00331.x","volume":"34","author":"PV Steagall","year":"2007","unstructured":"Steagall PV, Taylor PM, Brondani JT, Luna SP, Dixon MJ, Ferreira TH. Effects of buprenorphine, carprofen and saline on thermal and mechanical nociceptive thresholds in cats. Vet Anaesth Analg. 2007;34(5):344\u201350.","journal-title":"Vet Anaesth Analg"},{"issue":"2","key":"2735_CR25","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.tvjl.2008.06.017","volume":"182","author":"PV Steagall","year":"2009","unstructured":"Steagall PV, Mantovani FB, Taylor PM, Dixon MJ, Luna SP. Dose-related antinociceptive effects of intravenous buprenorphine in cats. Vet J. 2009;182(2):203\u20139.","journal-title":"Vet J"},{"issue":"1","key":"2735_CR26","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jfms.2007.06.009","volume":"10","author":"PV Steagall","year":"2008","unstructured":"Steagall PV, Taylor PM, Brondani JT, Luna SP, Dixon MJ. Antinociceptive effects of tramadol and acepromazine in cats. J Feline Med Surg. 2008;10(1):24\u201331.","journal-title":"J Feline Med Surg"},{"issue":"2","key":"2735_CR27","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/0006-8993(75)90005-0","volume":"98","author":"D Le Bars","year":"1975","unstructured":"Le Bars D, Mene D, Conseiller C, Besson J. Depressive effects of morphine upon lamina V cells activities in the dorsal horn of the spinal cat. Brain Res. 1975;98(2):261\u201377.","journal-title":"Brain Res"},{"issue":"1","key":"2735_CR28","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/S0304-3959(96)03177-6","volume":"68","author":"DC Yeomans","year":"1996","unstructured":"Yeomans DC, Proudfit HK. Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat: electrophysiological evidence. Pain. 1996;68(1):141\u201350.","journal-title":"Pain"},{"issue":"4","key":"2735_CR29","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1152\/jn.2000.83.4.2179","volume":"83","author":"R Slugg","year":"2000","unstructured":"Slugg R, Meyer R, Campbell JN. Response of cutaneous A-and C-fiber nociceptors in the monkey to controlled-force stimuli. J Neurophysiol. 2000;83(4):2179\u201391.","journal-title":"J Neurophysiol"},{"issue":"4","key":"2735_CR30","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/S0195-5616(08)70009-3","volume":"30","author":"MG Papich","year":"2000","unstructured":"Papich MG. Pharmacologic considerations for opiate analgesic and nonsteroidal anti-inflammatory drugs. Vet Clin North Am Small Anim Pract. 2000;30(4):815\u201337.","journal-title":"Vet Clin North Am Small Anim Pract"},{"issue":"1","key":"2735_CR31","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1146\/annurev.pa.28.040188.002241","volume":"28","author":"M Adler","year":"1988","unstructured":"Adler M, Geller E, Rosow C, Cochin J. The opioid system and temperature regulation. Annu Rev Pharmacol Toxicol. 1988;28(1):429\u201349.","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"8","key":"2735_CR32","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1292\/jvms.65.935","volume":"65","author":"R Refinetti","year":"2003","unstructured":"Refinetti R, Piccione G. Daily rhythmicity of body temperature in the dog. J Vet Med Sci. 2003;65(8):935\u20137.","journal-title":"J Vet Med Sci"},{"issue":"1","key":"2735_CR33","first-page":"329","volume":"248","author":"LJ Hellebrekers","year":"1989","unstructured":"Hellebrekers LJ, Vandenbrom WE, Mol JA. Plasma arginine vasopressin response to intravenous methadone and naloxone in conscious dogs. J Pharmacol Exp Ther. 1989;248(1):329\u201333.","journal-title":"J Pharmacol Exp Ther"},{"issue":"5","key":"2735_CR34","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1111\/j.1532-950X.1992.tb01719.x","volume":"21","author":"VS Copland","year":"1992","unstructured":"Copland VS, Haskins SC, Patz JD. Cardiovascular and pulmonary effects of atropine reversal of oxymorphone-induced bradycardia in dogs. Vet Surg. 1992;21(5):414\u20137.","journal-title":"Vet Surg"},{"issue":"1","key":"2735_CR35","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/BF00502575","volume":"312","author":"K Inoue","year":"1980","unstructured":"Inoue K, Samodelov L, Arndt J. Fentanyl activates a particular population of vagal efferents which are cardioinhibitory. Naunyn Schmiedeberg's Arch Pharmacol. 1980;312(1):57\u201361.","journal-title":"Naunyn Schmiedeberg's Arch Pharmacol"},{"issue":"6","key":"2735_CR36","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1111\/vaa.12257","volume":"42","author":"B KuKanich","year":"2015","unstructured":"KuKanich B, KuKanich K. Chloramphenicol significantly affects the pharmacokinetics of oral methadone in Greyhound dogs. Vet Anaesth Analg. 2015;42(6):597\u2013607.","journal-title":"Vet Anaesth Analg"},{"issue":"1","key":"2735_CR37","first-page":"109","volume":"207","author":"SC Schlitt","year":"1978","unstructured":"Schlitt SC, Schroeter LM, Wilson JE, Olsen GD. Methadone-induced respiratory depression in dog - comparison of steady-state and rebreathing techniques and correlation with serum drug concentration. J Pharmacol Exp Ther. 1978;207(1):109\u201322.","journal-title":"J Pharmacol Exp Ther"},{"key":"2735_CR38","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/9781119421375.ch11","volume-title":"Veterinary anesthesia and analgesia","author":"B KuKanich","year":"2015","unstructured":"KuKanich B, Wiese AJ. Opioids. In: Grimm KA, Lamont LA, Tranquilli WJ, Greene SA, Robertson SA, editors. Veterinary anesthesia and analgesia. 5th ed. Iowa: Wiley; 2015. p. 207\u201326.","edition":"5"},{"issue":"4","key":"2735_CR39","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/S0195-5616(08)70005-6","volume":"30","author":"PJ Pascoe","year":"2000","unstructured":"Pascoe PJ. Opioid analgesics. Vet Clin North Am Small Anim Pract. 2000;30(4):757\u201372.","journal-title":"Vet Clin North Am Small Anim Pract"},{"issue":"1","key":"2735_CR40","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.pharmthera.2007.09.007","volume":"117","author":"DL DeHaven-Hudkins","year":"2008","unstructured":"DeHaven-Hudkins DL, DeHaven RN, Little PJ, Techner LM. The involvement of the mu-opioid receptor in gastrointestinal pathophysiology: therapeutic opportunities for antagonism at this receptor. Pharmacol Ther. 2008;117(1):162\u201387.","journal-title":"Pharmacol Ther"},{"issue":"1","key":"2735_CR41","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1053\/j.gastro.2004.09.079","volume":"128","author":"X Xu","year":"2005","unstructured":"Xu X, Zhu H, Chen JD. Pyloric electrical stimulation reduces food intake by inhibiting gastric motility in dogs. Gastroenterology. 2005;128(1):43\u201350.","journal-title":"Gastroenterology"},{"issue":"3","key":"2735_CR42","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/0014-2999(86)90760-0","volume":"128","author":"JP Blancquaert","year":"1986","unstructured":"Blancquaert JP, Lefebvre RA, Willems JL. Emetic and antiemetic effects of opioids in the dog. Eur J Pharmacol. 1986;128(3):143\u201350.","journal-title":"Eur J Pharmacol"},{"issue":"4","key":"2735_CR43","first-page":"556","volume":"48","author":"JA Hall","year":"1987","unstructured":"Hall JA, Magne ML, Twedt DC. Effect of acepromazine, diazepam, fentanyl-droperidol, and oxymorphone on gastroesophageal sphincter pressure in healthy dogs. Am J Vet Res. 1987;48(4):556\u20137.","journal-title":"Am J Vet Res"},{"issue":"2","key":"2735_CR44","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1213\/00000539-199808000-00040","volume":"87","author":"IM Crighton","year":"1998","unstructured":"Crighton IM, Martin PH, Hobbs GJ, Cobby TF, Fletcher AJ, Stewart PD. A comparison of the effects of intravenous tramadol, codeine, and morphine on gastric emptying in human volunteers. Anesth Analg. 1998;87(2):445\u20139.","journal-title":"Anesth Analg"},{"issue":"1","key":"2735_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/ddr.430010102","volume":"1","author":"C Niemegeers","year":"1981","unstructured":"Niemegeers C, Colpaert F, Awouters F. Pharmacology and antidiarrheal effect of loperamide. Drug Dev Res. 1981;1(1):1\u201320.","journal-title":"Drug Dev Res"},{"issue":"5","key":"2735_CR46","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1111\/j.1365-2885.2005.00681.x","volume":"28","author":"B Kukanich","year":"2005","unstructured":"Kukanich B, Lascelles BD, Aman AM, Mealey KL, Papich MG. The effects of inhibiting cytochrome P450 3A, p-glycoprotein, and gastric acid secretion on the oral bioavailability of methadone in dogs. J Vet Pharmacol Ther. 2005;28(5):461\u20136.","journal-title":"J Vet Pharmacol Ther"},{"issue":"3","key":"2735_CR47","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1111\/j.1467-2995.2007.00369.x","volume":"35","author":"B KuKanich","year":"2008","unstructured":"KuKanich B, Borum SL. The disposition and behavioral effects of methadone in greyhounds. Vet Anaesth Analg. 2008;35(3):242\u20138.","journal-title":"Vet Anaesth Analg"},{"issue":"11","key":"2735_CR48","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1002\/jps.2600741114","volume":"74","author":"ER Garrett","year":"1985","unstructured":"Garrett ER, Derendorf H, Mattha AG. Pharmacokinetics of morphine and its surrogates. VII: high-performance liquid chromatographic analyses and pharmacokinetics of methadone and its derived metabolites in dogs. J Pharm Sci. 1985;74(11):1203\u201314.","journal-title":"J Pharm Sci"},{"issue":"7","key":"2735_CR49","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1023\/A:1018943613122","volume":"10","author":"B Davies","year":"1993","unstructured":"Davies B, Morris T. Physiological parameters in laboratory animals and humans. Pharm Res. 1993;10(7):1093\u20135.","journal-title":"Pharm Res"},{"issue":"4","key":"2735_CR50","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1111\/j.1467-2995.2005.00266.x","volume":"33","author":"T Sano","year":"2006","unstructured":"Sano T, Nishimura R, Kanazawa H, Igarashi E, Nagata Y, Mochizuki M, et al. Pharmacokinetics of fentanyl after single intravenous injection and constant rate infusion in dogs. Vet Anaesth Analg. 2006;33(4):266\u201373.","journal-title":"Vet Anaesth Analg"},{"issue":"3","key":"2735_CR51","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1258\/la.2010.009080","volume":"44","author":"MJ Dixon","year":"2010","unstructured":"Dixon MJ, Taylor PM, Slingsby L, Hoffmann MV, Kastner SB, Murrell J. A small, silent, low friction, linear actuator for mechanical nociceptive testing in veterinary research. Lab Anim. 2010;44(3):247\u201353.","journal-title":"Lab Anim"},{"issue":"9","key":"2735_CR52","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.2460\/ajvr.70.9.1065","volume":"70","author":"RJ Brosnan","year":"2009","unstructured":"Brosnan RJ, Pypendop BH, Siao KT, Stanley SD. Effects of remifentanil on measures of anesthetic immobility and analgesia in cats. Am J Vet Res. 2009;70(9):1065\u201371.","journal-title":"Am J Vet Res"},{"issue":"10","key":"2735_CR53","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.2460\/javma.237.10.1155","volume":"237","author":"EH Hofmeister","year":"2010","unstructured":"Hofmeister EH, Chandler MJ, Read MR. Effects of acepromazine, hydromorphone, or an acepromazine-hydromorphone combination on the degree of sedation in clinically normal dogs. J Am Vet Med Assoc. 2010;237(10):1155\u20139.","journal-title":"J Am Vet Med Assoc"},{"key":"2735_CR54","unstructured":"Gabrielsson J, Weiner D. Pharmacokinetic and pharmacodynamic data analysis: concepts and applications. 3rd ed. Stockholm: CRC Press; 2001."}],"container-title":["BMC Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-020-02735-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12917-020-02735-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-020-02735-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T23:15:13Z","timestamp":1697584513000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcvetres.biomedcentral.com\/articles\/10.1186\/s12917-020-02735-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,18]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["2735"],"URL":"https:\/\/doi.org\/10.1186\/s12917-020-02735-3","relation":{},"ISSN":["1746-6148"],"issn-type":[{"value":"1746-6148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,18]]},"assertion":[{"value":"10 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Approved by the ethical committee of the Lower Saxony State Office for Consumer Protection and Food Safety according to the German animal welfare act (approval number 33.12-42502-04-14\/1733).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"35"}}