{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:48:58Z","timestamp":1777909738724,"version":"3.51.4"},"reference-count":44,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T00:00:00Z","timestamp":1386633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T00:00:00Z","timestamp":1386633600000},"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":[[2014,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>A new gel formulation containing loteprednol etabonate (LE), a C-20 ester corticosteroid used to treat ocular inflammation, was developed to provide increased retention on the ocular surface for improved drug delivery to intraocular tissues. This investigation evaluated concentrations of LE in tear fluid following topical instillation of LE gel to humans and the ocular and systemic pharmacokinetics of LE following administration to rabbits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      LE ophthalmic gel 0.5% was administered as a single topical dose to human volunteers (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =12) and Dutch Belted rabbits (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =40). In the human study, tear sampling was performed at 6, 9, 12, and 24\u2009h after instillation. In the rabbit study, tears and ocular tissues were collected from 5\u2009min through 24\u2009h postdose. Serial blood samples were collected from one cohort of rabbits for plasma analysis. Concentrations of LE were determined by high performance liquid chromatography tandem mass spectrometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In humans, LE was detected in tears at all the time points assessed with mean concentrations of 114\u2009\u03bcg\/g at 6\u2009h declining to 2.41\u2009\u03bcg\/g at 24\u2009h postdose. In rabbits, LE was detected in all ocular tissues within 5\u2009min after dosing. Maximum concentrations of LE were achieved within 0.5\u2009h and were highest in tear fluid (1560\u2009\u03bcg\/g), followed by bulbar conjunctiva (4.03\u2009\u03bcg\/g), cornea, (2.18\u2009\u03bcg\/g), iris\/ciliary body (0.162\u2009\u03bcg\/g), and aqueous humor (0.0138\u2009\u03bcg\/mL). LE remained measurable in all ocular tissues through 24\u2009h with the exception of aqueous humor. In contrast, plasma levels of LE were low with no detectable levels after 4\u2009h.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The gel formulation of LE provided prolonged exposure to LE on the ocular surface, with measurable levels in tears through 24\u2009h in both humans and rabbits, for delivery of LE to anterior segment tissues, as evidenced by sustained levels of LE in rabbit conjunctiva, cornea, and iris\/ciliary body.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2013.0142","type":"journal-article","created":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T09:32:30Z","timestamp":1386667950000},"page":"66-73","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Prolonged Exposure to Loteprednol Etabonate in Human Tear Fluid and Rabbit Ocular Tissues Following Topical Ocular Administration of Lotemax Gel, 0.5%"],"prefix":"10.1177","volume":"30","author":[{"given":"Shellise","family":"Glogowski","sequence":"first","affiliation":[{"name":"Bausch & Lomb, Inc.,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ezra","family":"Lowe","sequence":"additional","affiliation":[{"name":"Bausch & Lomb, Inc.,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphaele","family":"Siou-Mermet","sequence":"additional","affiliation":[{"name":"Bausch & Lomb, Inc.","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuyen","family":"Ong","sequence":"additional","affiliation":[{"name":"Bausch & Lomb, Inc."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Richardson","sequence":"additional","affiliation":[{"name":"Bausch & Lomb, Inc."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2013,12,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00188"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0039-6257(93)90141-S"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-010-9183-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/IJG.0b013e31814b990d"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/0192623307310955"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389200033489488"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/jop.1995.11.297"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2000.03288.x"},{"key":"e_1_3_3_10_2","first-page":"264","article-title":"Determination of tear volume and tear flow","volume":"5","author":"Mishima S.","year":"1966","unstructured":"Mishima S., , Gasset A., , Klyce S.D., , and Baum J.L., Determination of tear volume and tear flow. 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