{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:14:32Z","timestamp":1791317672791,"version":"4.3.1"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Daily oral cyclobenzaprine hydrochloride (HCl) has provided transient benefits in fibromyalgia, a chronic pain condition. To improve this effect, we evaluated sublingual formulations designed to drive transmucosal absorption. Two open\u2010label studies evaluated the pharmacokinetics (PK), tolerability, and relative bioavailability of sublingual cyclobenzaprine HCl in healthy adults. In Study 1 (n = 24), three 2.8\u00a0mg sublingual formulations of cyclobenzaprine HCl containing potassium phosphate dibasic (A), sodium phosphate dibasic (B), or trisodium citrate (C) were compared to immediate release (IR) cyclobenzaprine HCl 5\u00a0mg. All sublingual formulations showed increased bioavailability (154% [A], 126% [B], and 125% [C]) and rapid absorption. Formulation A demonstrated the most favorable PK, with a \u223c3\u00a0min absorption lag versus \u223c37\u00a0min for oral IR, and a 783% higher dose\u2010normalized AUC\n                    <jats:sub>0\u20101<\/jats:sub>\n                    . Formulation A was designated TNX\u2010102 SL for further development. In Study 2 (n = 16), TNX\u2010102 SL 2.8 and 5.6\u00a0mg exhibited dose proportionality and no food effect. Furthermore, this is the first report describing the active metabolite norcyclobenzaprine in clinical studies, showing an elimination half\u2010life of \u223c60 h. Oral hypoesthesia and abnormal taste were the most common adverse events. These findings support TNX\u2010102 SL as a rapidly absorbed and efficient sublingual tablet formulation of cyclobenzaprine HCl, providing effective transmucosal delivery.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.70034","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:25:47Z","timestamp":1772969147000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010Dose Pharmacokinetic Assessment of TNX\u2010102 SL (Cyclobenzaprine HCl Sublingual Tablets): Results From Randomized, Open\u2010Label Studies in Healthy Volunteers"],"prefix":"10.1002","volume":"15","author":[{"given":"Bruce L","family":"Daugherty","sequence":"first","affiliation":[{"name":"Tonix Pharmaceuticals Inc. Berkeley Heights NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Meibohm","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Science Center  Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Tonix Pharmaceuticals Inc. Berkeley Heights NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Errol M","family":"Gould","sequence":"additional","affiliation":[{"name":"Tonix Medicines, Inc  Berkeley Heights NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Lederman","sequence":"additional","affiliation":[{"name":"Tonix Pharmaceuticals Inc. Berkeley Heights NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21896"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2016.08.012"},{"key":"e_1_2_10_4_1","unstructured":"Tonix Pharmaceuticals Holding Corp.Tonix pharmaceuticals announces FDA approval of Tonmya\u2122 (cyclobenzaprine HCl sublingual tablets) for the treatment of fibromyalgia. Tonix Pharmaceuticals. Accessed September 3 2025.https:\/\/ir.tonixpharma.com\/news\u2010events\/press\u2010releases\/detail\/1585\/tonix\u2010pharmaceuticals\u2010announces\u2010fda\u2010approval\u2010of."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/pme.12168"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.5055\/jom.2019.0537"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102011\u2010201249"},{"key":"e_1_2_10_8_1","unstructured":"Pharmascience Inc.Cyclobenzaprine hydrochloride (cyclobenzaprine HCL). Full Prescribing Information. Pharmascience Inc; 2023."},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780370106"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780311210"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.110194"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-9556(25)07430-6"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13091409"},{"key":"e_1_2_10_14_1","volume-title":"StatPearls","author":"Khan I","year":"2024"},{"key":"e_1_2_10_15_1","unstructured":"SullivanG KiuR StillwellH MeibohmB LedermanS.Steady\u2010state pharmacokinetic properties of a sublingual formulation of cyclobenzaprine (CBP) HCl (TNX\u2010102 SL*): comparison to simulations of oral immediate release CBP. Paper presented at: American Society of Clinical Psychopharmacology; May 28\u201031 2019; Scottsdale AZ."},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.25142"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/pm\/pnaf089"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2011.12.003"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2012.08.001"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386\u2010020\u201000812\u20107"},{"key":"e_1_2_10_21_1","unstructured":"DaughertyB GershellL LedermanS.Cyclobenzaprine (CBP) and its major metabolite norcyclobenzaprine (nCBP) are potent antagonists of human serotonin receptor 2a (5HT2a) histamine receptor H\u20101 and alpha\u2010adrenergic receptors: mechanistic and safety implications for treating fibromyalgia syndrome by improving sleep quality [abstract 960]. Paper presented at: ACR\/ARHP Annual Meeting; November 9\u201314 2012; Washington DC."},{"key":"e_1_2_10_22_1","unstructured":"DaughertyB SullivanG GershellL LedermanS.Serotonin receptor profiles of bedtime pharmacotherapies targeting posttraumatic stress disorder (PTSD) [abstract #728]. Paper presented at: Society of Biological Psychiatry 70th Annual Scientific Convention; May 14\u201016 2015; Toronto ON Canada."},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)10356-X"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(89)91546\u20101"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)30185-0"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1098\u20107339(03)00194\u20109"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13004"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70034","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.70034","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T13:48:54Z","timestamp":1774360134000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.70034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/cpdd.70034"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.70034","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]},"assertion":[{"value":"2025-10-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70034"}}