{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:19:24Z","timestamp":1784697564691,"version":"3.55.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T00:00:00Z","timestamp":1628380800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T00:00:00Z","timestamp":1628380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Drug Investig"],"published-print":{"date-parts":[[2021,9]]},"DOI":"10.1007\/s40261-021-01066-x","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T17:07:26Z","timestamp":1628615246000},"page":"817-823","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Efficacy and Tolerability of Oral Compared with Sublingual Ketamine Lozenges as Rescue Analgesics in Adults for Acute Pain: The OSKet Trial"],"prefix":"10.1007","volume":"41","clinical-trial-number":[{"clinical-trial-number":"actrn12621000240842","registry":"10.18810\/anzctr"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7465-538X","authenticated-orcid":false,"given":"Chui C.","family":"Chong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0302-2315","authenticated-orcid":false,"given":"Stephan A.","family":"Schug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,8]]},"reference":[{"key":"1066_CR1","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1111\/cns.12111","volume":"19","author":"J Persson","year":"2013","unstructured":"Persson J. Ketamine in pain management. CNS Neurosci Ther. 2013;19:396\u2013402.","journal-title":"CNS Neurosci Ther"},{"key":"1066_CR2","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.pain.2008.12.003","volume":"141","author":"RF Bell","year":"2009","unstructured":"Bell RF. Ketamine for chronic non-cancer pain. Pain. 2009;141:210\u20134.","journal-title":"Pain"},{"key":"1066_CR3","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1111\/bcp.12094","volume":"77\u20132","author":"M Niesters","year":"2014","unstructured":"Niesters M, Martini C, Dahan A. Ketamine for chronic pain: risks and benefits. Br J of Clin Pharmacol. 2014;77\u20132:357\u201367.","journal-title":"Br J of Clin Pharmacol"},{"key":"1066_CR4","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1517\/14656566.2010.515978","volume":"11","author":"I Noppers","year":"2010","unstructured":"Noppers I, Niesters M, Aarts L, Smith T, Sarton E, Dahan A. Ketamine for the treatment of chronic non-cancer pain. Expert Opin Pharmacother. 2010;11:2417\u201329.","journal-title":"Expert Opin Pharmacother"},{"key":"1066_CR5","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1111\/pme.12619","volume":"16","author":"J Jouguelet-Lacoste","year":"2015","unstructured":"Jouguelet-Lacoste J, La Colla L, Chelly J. The use of intravenous infusion or single dose of low-dose ketamine for postoperative analgesia: a review of current literature. Pain Med. 2015;16:383\u2013403.","journal-title":"Pain Med"},{"key":"1066_CR6","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1007\/s12630-011-9560-0","volume":"58","author":"K Laskowski","year":"2011","unstructured":"Laskowski K, Stirling A, McKay WP, Lim HJ. A systematic review of intravenous ketamine for postoperative analgesia. Can J Anaesth. 2011;58:911\u201323.","journal-title":"Can J Anaesth"},{"key":"1066_CR7","doi-asserted-by":"crossref","unstructured":"Chaparro LE, Smith SA, Moore RA, Wiffen PJ, Gilron I. Pharmacotherapy for the prevention of chronic pain after surgery in adults. Cochrane Database of Systematic Reviews 2013;(7). Art. No.: CD008307.","DOI":"10.1002\/14651858.CD008307.pub2"},{"key":"1066_CR8","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.jpainsymman.2005.04.014","volume":"30","author":"S Mercandante","year":"2005","unstructured":"Mercandante S, Arcure E, Ferrera P, Villari P, Mangione S. Alternative treatments of breakthrough pain in patients receiving spinal analgesics for Cancer pain. J Pain Symptom Manag. 2005;30:485\u201391.","journal-title":"J Pain Symptom Manag"},{"key":"1066_CR9","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1111\/pme.12182","volume":"14","author":"AL Bredlau","year":"2013","unstructured":"Bredlau AL, Tahnku R, Korones DN, Dworkin RH. Ketamine for pain in adults and children with cancer: a systematic review and synthesis of the literature. Pain Med. 2013;14:1505\u201317.","journal-title":"Pain Med"},{"key":"1066_CR10","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1111\/j.1526-4637.2007.00314.x","volume":"9","author":"P Cvrcek","year":"2008","unstructured":"Cvrcek P. Side effects of ketamine in long-term treatment of neuropathic pain. Pain Med. 2008;9:253\u20137.","journal-title":"Pain Med"},{"issue":"2","key":"1066_CR11","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s11916-018-0664-x","volume":"22","author":"J Zhao","year":"2018","unstructured":"Zhao J, Wang Y, Wang D. The effect of ketamine infusion in the treatment of complex regional pain syndrome: a systemic review and meta-analysis. Curr Pain Headache Rep. 2018;22(2):12.","journal-title":"Curr Pain Headache Rep"},{"issue":"5","key":"1066_CR12","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1111\/pme.12675","volume":"16","author":"SB Connolly","year":"2015","unstructured":"Connolly SB, Prager JP, Harden RN. A systematic review of ketamine for complex regional pain syndrome. Pain Med. 2015;16(5):943\u201369.","journal-title":"Pain Med"},{"key":"1066_CR13","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1177\/1049909111416345","volume":"29","author":"E Soto","year":"2012","unstructured":"Soto E, Stewart DR, Mannes AJ, Ruppert SL, Baker K, Zlott D, Handel D, Berger AH. Oral ketamine in the palliative care setting: a review of the literature and case report of a patient with neurofibromatosis type 1 and glomus tumor-associated complex regional pain syndrome. Am J Hosp Palliat Care. 2012;29:308\u201317.","journal-title":"Am J Hosp Palliat Care"},{"issue":"7","key":"1066_CR14","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1002\/ejp.624","volume":"19","author":"F Marchetti","year":"2015","unstructured":"Marchetti F, Coutaux A, Bellanger A, Magneux C, Bourgeois P, Mion G. Efficacy and safety of oral ketamine for the relief of intractable chronic pain: a retrospective 5-year study of 51 patients. Eur J Pain. 2015;19(7):984\u201393.","journal-title":"Eur J Pain."},{"issue":"5","key":"1066_CR15","doi-asserted-by":"publisher","first-page":"379","DOI":"10.5055\/jom.2013.0180","volume":"9","author":"QA Tawfic","year":"2013","unstructured":"Tawfic QA. A review of the use of ketamine in pain management. J Opioid Manag. 2013;9(5):379\u201388.","journal-title":"J Opioid Manag."},{"issue":"5","key":"1066_CR16","doi-asserted-by":"publisher","first-page":"e674","DOI":"10.1097\/PR9.0000000000000674","volume":"3","author":"RF Bell","year":"2018","unstructured":"Bell RF, Kalso EA. Ketamine for pain management. Pain Rep. 2018;3(5):e674.","journal-title":"Pain Rep"},{"key":"1066_CR17","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.tacc.2014.03.002","volume":"4","author":"J Sleigh","year":"2014","unstructured":"Sleigh J, Harvey M, Voss L, Denny B. Ketamine\u2014more mechanisms of action than just NMDA blockade. Trends Anaesth Crit Care. 2014;4:76\u201381.","journal-title":"Trends Anaesth Crit Care"},{"key":"1066_CR18","doi-asserted-by":"publisher","first-page":"317","DOI":"10.2165\/00044011-200929050-00004","volume":"29","author":"C Chong","year":"2009","unstructured":"Chong C, Schug SA, Page-Sharp M, Jenkins B, Illett KF. Development of sublingual\/oral formulation of ketamine for use in neuropathic pain: preliminary findings from a three-way randomized, crossover study. Clin Drug Investig. 2009;29:317\u201324.","journal-title":"Clin Drug Investig"},{"key":"1066_CR19","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1111\/bcp.12264","volume":"77","author":"P Rolan","year":"2014","unstructured":"Rolan P, Lim S, Sunderland V, Liu Y, Molnar V. The absolute bioavailability of racemic ketamine from a novel sublingual formulation. Br J Clin Pharmacol. 2014;77:1011\u20136.","journal-title":"Br J Clin Pharmacol"},{"key":"1066_CR20","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1002\/bdd.336","volume":"24","author":"Y Yanagihara","year":"2003","unstructured":"Yanagihara Y, Ohtani M, Kariya S, Uchino K, Hiraishi T, Ashizawa N, Aoyama T, Yamamura Y, Yamada Y, Iga T. Plasma concentration profiles of ketamine and norketamine after administration of various ketamine preparations to healthy Japanese volunteers. Biopharm Drug Dispos. 2003;24:37\u201343.","journal-title":"Biopharm Drug Dispos"},{"key":"1066_CR21","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1007\/s40262-016-0383-6","volume":"55","author":"MA Peltoniemi","year":"2016","unstructured":"Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: a review of clinical pharmacokinetics and pharmacodynamics in anesthesia and pain therapy. Clin Pharmacokinet. 2016;55:1059\u201377.","journal-title":"Clin Pharmacokinet"},{"key":"1066_CR22","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S0014-2999(97)01116-3","volume":"333","author":"B Ebert","year":"1997","unstructured":"Ebert B, Mikkelsen S, Thorkildsen C, Borgbjerg FM. Norketamine, the main metabolite of ketamine, is a non-competitive NMDA receptor antagonist in the rat cortex and spinal cord. Eur J Pharmacol. 1997;333:99\u2013104.","journal-title":"Eur J Pharmacol"},{"key":"1066_CR23","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0304-3959(98)00269-3","volume":"81","author":"M Shimoyama","year":"1999","unstructured":"Shimoyama M, Shimoyama N, Gorman AL, Elliott KJ, Inturrisi CE. Oral ketamine is antinociceptive in the rat formalin test: role of the metabolite, norketamine. Pain. 1999;81:85\u201393.","journal-title":"Pain"},{"key":"1066_CR24","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1097\/ALN.0b013e31825b6c91","volume":"117","author":"E Olefsen","year":"2012","unstructured":"Olefsen E, Noppers I, Niesters M, Kharasch E, Aarts L, Sarton E, Dahan A. Estimation of the contribution of norketamine to ketamine-induced acute pain relief and neurocognitive impairment in healthy volunteers. Anaesthesiology. 2012;117:353\u201364.","journal-title":"Anaesthesiology"},{"key":"1066_CR25","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1586\/14737175.2014.971760","volume":"14","author":"NS Singh","year":"2014","unstructured":"Singh NS, Zarate CA Jr, Moaddel R, Bernier M, Wainer IW. What is hydroxynorketamine and what can it bring to neurotherapeutics? Expert Rev Neurother. 2014;14:1239\u201342.","journal-title":"Expert Rev Neurother"},{"key":"1066_CR26","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature17998","volume":"533","author":"P Zanos","year":"2016","unstructured":"Zanos P, Moaddel R, Morris PJ, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature. 2016;533:481\u20136.","journal-title":"Nature"},{"issue":"5","key":"1066_CR27","first-page":"521","volume":"43","author":"SP Cohen","year":"2018","unstructured":"Cohen SP, Bhatia A, Buvanendran A, Schwenk ES, Wasan AD, Hurley RW, Viscusi ER, Narouze S, Davis FN, Ritchie EC, Lubenow TR, Hooten WM. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018;43(5):521\u201346.","journal-title":"Reg Anesth Pain Med."},{"key":"1066_CR28","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1002\/jps.2600710516","volume":"71","author":"JA Clements","year":"1982","unstructured":"Clements JA, Nimmo WA, Grant IS. Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. J Pharm Sci. 1982;71:539\u201342.","journal-title":"J Pharm Sci"},{"key":"1066_CR29","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1124\/pr.117.015198","volume":"70","author":"P Zanos","year":"2018","unstructured":"Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgious P, Perreira EFR, Albuquerque EX, Thomas CJ, Zarate CA, Gould TD. Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms. Pharmacol Rev. 2018;70:621\u201360.","journal-title":"Pharmacol Rev"},{"key":"1066_CR30","first-page":"456","volume":"43","author":"ES Schewenk","year":"2018","unstructured":"Schewenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP. Consensus guidelines on the use of intravenous ketamine infusions for acute pain management and pain medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018;43:456\u201366.","journal-title":"Reg Anesth Pain Med"}],"container-title":["Clinical Drug Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40261-021-01066-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40261-021-01066-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40261-021-01066-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T11:28:06Z","timestamp":1629977286000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40261-021-01066-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,8]]},"references-count":30,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["1066"],"URL":"https:\/\/doi.org\/10.1007\/s40261-021-01066-x","relation":{},"ISSN":["1173-2563","1179-1918"],"issn-type":[{"value":"1173-2563","type":"print"},{"value":"1179-1918","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,8]]},"assertion":[{"value":"20 July 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"University of Western Australia, Discipline of Anaesthesiology and Pain Medicine, Level 4 MRF Building, Royal Perth Hospital, GPO BOX X2213 Perth WA 6847 Australia.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Dr. Chui Chong: None. Prof S. Schug: The Anaesthesiology Unit of the University of Western Australia (and Professor Schug personally since his retirement in October 2019) has received research and travel funding, speaking and consulting honoraria from Eli Lilly, Grunenthal, Indivior, Jansseen, Mundipharma, Pfizer, Phosphagenics, iXBiopharma, Seqirus, Xgene, Biogen, Luye Pharma and Foundry within the last 5 years. None of this funding was related to this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures in this study were in accordance with the 1964 Helsinki Declaration (and its amendments), and overseen by Royal Perth Hospital Human Research Ethic Committee","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethic approval"}},{"value":"Informed consent was obtained from all individual participants included in this study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The datasets generated during and\/or analysed during the current study can be made available from the corresponding author on reasonable request within 5 years of publication.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data transparency"}},{"value":"All data generated or analysed during the current study are included in this published article.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"Study design and ethics approval obtained by SS. CC recruited subjects and collected data. Data analysed and paper written by CC and SS.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 contributions"}}]}}