{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:44:31Z","timestamp":1782362671917,"version":"3.54.5"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,2,17]],"date-time":"2020-02-17T00:00:00Z","timestamp":1581897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Douglas Pharmaceuticals Ltd"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Parenteral ketamine has fast\u2010onset antidepressant and antianxiety effects; however, it causes dissociation, hypertension, and tachycardia shortly after dosing. Ketamine's antidepressant effects may be due to active metabolites rather than to ketamine itself. We hypothesized that oral controlled\u2010release ketamine tablets would improve safety and tolerability compared with injected ketamine by reducing peak ketamine exposures compared with dosing by injection. In this randomized, placebo\u2010controlled ascending\u2010dose study, ketamine doses of 60, 120, or 240 mg or matching placebo (single dose followed by every\u201012\u2010hours dosing for 5 doses) were given to 24 healthy volunteers. Pharmacokinetics, pharmacodynamics (brain\u2010derived neurotropic factor), adverse events, and vital signs were assessed up to 72\u00a0hours. Drug release occurred over \u223c10 hours, with most drug substance present as norketamine (\u223c90%). Area under the concentration\u2010time curve and peak concentration were dose proportional. Elimination half\u2010life was prolonged (7\u20109 hours) compared with published data from immediate\u2010release oral formulations. There were no changes in blood pressure or heart rate after any dose. Mild dissociation was reported after 240 mg but not lower doses; mean dissociation ratings in this group were minimal (1\u20102\/76). There were no clinically significant changes in ECGs or safety laboratory tests at any time. Compared with injected ketamine, oral controlled\u2010release ketamine tablets did not increase blood pressure or heart rate, and only at doses of 240 mg was dissociation of mild intensity reported. Reducing and delaying ketamine peak concentration by oral dosing with controlled\u2010release ketamine tablets improve this drug's tolerability for patients with depression\/anxiety.<\/jats:p>","DOI":"10.1002\/jcph.1573","type":"journal-article","created":{"date-parts":[[2020,2,17]],"date-time":"2020-02-17T12:39:50Z","timestamp":1581943190000},"page":"751-757","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Ascending\u2010Dose Study of Controlled\u2010Release Ketamine Tablets in Healthy Volunteers: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability"],"prefix":"10.1002","volume":"60","author":[{"given":"Paul","family":"Glue","sequence":"first","affiliation":[{"name":"Psychological Medicine University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie J.","family":"Medlicott","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Surman","sequence":"additional","affiliation":[{"name":"Douglas Pharmaceuticals  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Lam","sequence":"additional","affiliation":[{"name":"Zenith Technology Ltd  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelyn","family":"Hung","sequence":"additional","affiliation":[{"name":"Zenith Technology Ltd  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Tak","family":"Hung","sequence":"additional","affiliation":[{"name":"Zenith Technology Ltd  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyv124"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1903305"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/acps.12572"},{"key":"e_1_2_9_5_1","article-title":"Effects of ketamine in patients with treatment\u2010refractory generalized anxiety and social anxiety disorders: exploratory double\u2010blind psychoactive\u2010controlled replication study","author":"Glue P","journal-title":"J Psychopharmacol."},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000000285"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17998"},{"key":"e_1_2_9_8_1","unstructured":"GluePW MedlicottNJ SurmanP.Extended release pharmaceutical formulation.U.S. Patent US2019\/10441544 B2 (2019)."},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145713001119"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1024465317902"},{"key":"e_1_2_9_11_1","volume-title":"Columbia\u2010Suicide Severity Rating Scale (C\u2010SSRS)","author":"Posner K","year":"2008"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1994.03950030035004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.115.165498"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.2018.196"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.336"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12264"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2165\/00044011-200929050-00004"},{"issue":"3","key":"e_1_2_9_18_1","first-page":"4335","article-title":"Assessment of the effect of ketamine on cytochrome P450 isoforms activity in rats by cocktail method","volume":"8","author":"Lin F","year":"2015","journal-title":"Int J Clin Exp Med"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.255"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4786-3"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2018.02.056"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.1573","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1573","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.1573","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1573","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T02:19:38Z","timestamp":1693966778000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,17]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1002\/jcph.1573"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1573","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,17]]},"assertion":[{"value":"2019-10-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}