{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:10:42Z","timestamp":1779253842507,"version":"3.51.4"},"reference-count":17,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2016,4,5]],"date-time":"2016-04-05T00:00:00Z","timestamp":1459814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2016,4,5]],"date-time":"2016-04-05T00:00:00Z","timestamp":1459814400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2016,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>\n                      To investigate the safety, tolerability, and pharmacokinetics of trabodenoson, a highly selective adenosine mimetic targeting the adenosine A\n                      <jats:sub>1<\/jats:sub>\n                      receptor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In Part 1, 60 healthy adult volunteers were randomized to 14 days of twice-daily topical monocular application of placebo or trabodenoson (200, 400, 800, 1,600, 2,400, or 3,200\u2009\u03bcg). In Part 2, 10 subjects were randomized to placebo or 8 escalating doses of bilateral trabodenoson (total daily doses: 1,800\u20136,400\u2009\u03bcg).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The incidence of treatment-related adverse events in Part 1 was similar in the trabodenoson (27.8%) and placebo (25.0%) groups. Most were mild in intensity. The most common adverse events (AEs) for trabodenoson and placebo were headache (25.0% vs. 33%, respectively) and eye pain (11.1% vs. 4.2%, respectively). Ocular AEs were infrequent (16.7% and 17.9%, respectively), were self-limited, lasted &lt;24\u2009h, and were typically mild in intensity. The most common ocular AE was eye pain (9.5% and 3.6%, respectively), with a single observation of ocular hyperemia (200\u2009\u03bcg trabodenoson). Trabodenoson was rapidly absorbed [median time to maximum concentration (t\n                      <jats:sub>max<\/jats:sub>\n                      ): \u223c0.08 to 0.27\u2009h] and eliminated (t\n                      <jats:sub>\u00bd<\/jats:sub>\n                      : 0.48\u20132.0\u2009h), with no evidence of drug accumulation. Systemic exposure to topical trabodenoson was dose related but not dose proportional, with a plateau effect at doses \u22652,400\u2009mg per eye. No clinically significant treatment-related systemic AEs were observed, and increasing systemic exposure had no effect on heart rate or blood pressure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Ocular doses of trabodenoson up to 3,200\u2009\u03bcg per eye were safe and well tolerated in the eye and resulted in no detectable systemic effects in healthy adult volunteers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2015.0147","type":"journal-article","created":{"date-parts":[[2016,4,5]],"date-time":"2016-04-05T16:16:02Z","timestamp":1459872962000},"page":"548-554","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["A Randomized Phase 1 Dose Escalation Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Trabodenoson in Healthy Adult Volunteers"],"prefix":"10.1177","volume":"32","author":[{"given":"Alan","family":"Laties","sequence":"first","affiliation":[{"name":"Scheie Eye Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cadmus C.","family":"Rich","sequence":"additional","affiliation":[{"name":"Inotek Pharmaceuticals Corporation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randall","family":"Stoltz","sequence":"additional","affiliation":[{"name":"Covance Global Clinical Pharmacology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vernon","family":"Humbert","sequence":"additional","affiliation":[{"name":"Evansville Heart Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaim","family":"Brickman","sequence":"additional","affiliation":[{"name":"Inotek Pharmaceuticals Corporation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"McVicar","sequence":"additional","affiliation":[{"name":"Inotek Pharmaceuticals Corporation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudolf A.","family":"Baumgartner","sequence":"additional","affiliation":[{"name":"Inotek Pharmaceuticals Corporation"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,4,5]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.120.6.714"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.120.6.701"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.121.1.48"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.120.10.1268"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2010.20"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2014.08.009"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704267"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1997.0296"},{"key":"e_1_3_2_10_2","first-page":"1833","article-title":"Characterization of ocular hypertension induced by adenosine agonists","volume":"37","author":"Crosson C.E.","year":"1996","unstructured":"Crosson C.E., , and Gray T. 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