{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:57:21Z","timestamp":1791619041587,"version":"4.3.4"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T00:00:00Z","timestamp":1562544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>TRV734 is an orally bioavailable G\u2010protein\u2013biased ligand at the \u03bc\u2010opioid receptor. In nonclinical studies it was potently analgesic while causing less gastrointestinal dysfunction than morphine, suggesting unique benefits in acute pain management. A 2\u2010part, first\u2010in\u2010human study was conducted with ascending doses of TRV734 to explore its tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers. TRV734 was well tolerated over the dose range 2 to 250\u00a0mg when administered orally. Plasma TRV734 maximum concentration and area under the plasma concentration\u2013time curve generally increased with dose, while time to maximum concentration was similar across doses (0.5\u20131.3\u00a0h). The half\u2010life increased with dose from 10\u00a0mg through 150\u00a0mg (0.75\u20132.28\u00a0h) but was similar from 150\u00a0mg through 250\u00a0mg. Pupil constriction, confirming central nervous system \u03bc\u2010opioid receptor engagement, correlated with higher plasma TRV734 concentrations; the greatest reductions in pupil diameter occurring between 0 and 4 hours after dosing (\u20132.9\u00a0mm\/h, with reduction peaking at 1 hour, and returning to baseline by 8 hours). Following administration of TRV734 125\u00a0mg under fasted or fed conditions, there was no significant difference in bioavailability when given as a solution or drug in capsule to fasted subjects. When drug in capsule was given to subjects following a high\u2010fat meal, absorption was slowed, resulting in decreased peak concentrations, but area under the plasma concentration\u2013time curve was not affected.<\/jats:p>","DOI":"10.1002\/cpdd.721","type":"journal-article","created":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T06:38:49Z","timestamp":1562654329000},"page":"256-266","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["A First\u2010in\u2010Human Clinical Study With TRV734, an Orally Bioavailable G\u2010Protein\u2013Biased Ligand at the \u03bc\u2010Opioid Receptor"],"prefix":"10.1002","volume":"9","author":[{"given":"Ian E.","family":"James","sequence":"first","affiliation":[{"name":"Trevena, Inc  Chesterbrook PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Skobieranda","sequence":"additional","affiliation":[{"name":"Trevena, Inc  Chesterbrook PA USA"},{"name":"Flourtown  PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Soergel","sequence":"additional","affiliation":[{"name":"Trevena, Inc  Chesterbrook PA USA"},{"name":"Novartis  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Trevena, Inc  Chesterbrook PA USA"},{"name":"Intact Vascular  Wayne PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Ruff","sequence":"additional","affiliation":[{"name":"ICON Early Phase Services  San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Fossler","sequence":"additional","affiliation":[{"name":"Trevena, Inc  Chesterbrook PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1054\/jpai.2002.123652"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2009.09.028"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.36076\/ppj.2008\/11\/S105"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0885-3924(90)90031-E"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000068822.10113.9E"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5449.2495"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms10030954"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.087254"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.201616"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.06.011"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S137952"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.040352"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.06.006"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.69.022405.154749"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011407496"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(85)90232-5"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-6576.2000.440420.x"},{"issue":"1","key":"e_1_2_7_19_1","first-page":"150","article-title":"The development and use of the Stanford Sleepiness Scale (SSS)","volume":"9","author":"Hoddes E","year":"1972","journal-title":"Psychophysiology."},{"key":"e_1_2_7_20_1","article-title":"Public health responses to the opioid crisis in North America","author":"Kerr T","journal-title":"J Epidemiol Comm Health."},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.1997.tb02866.x"},{"key":"e_1_2_7_22_1","unstructured":"BossertJM HootsJK NegusSS et\u00a0al.Modeling opioid maintenance therapy in rats: Effects of chronic buprenorphine and the biased mu opioid receptor agonist TRV130 on relapse to oxycodone seeking. 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