{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:20:57Z","timestamp":1784546457760,"version":"3.55.0"},"reference-count":15,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"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":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>Evaluate the ocular distribution, tolerability, and systemic exposure of cyclosporine (CsA) in New Zealand white rabbits following topical administration of OTX-101, a novel, clear aqueous nanomicellar solution developed for the treatment of dry eye disease (DED).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      The study design included single- and repeat-dose phases. In the single-dose phase, rabbits received a single instillation of OTX-101 0.05% or CsA ophthalmic emulsion 0.05% (Restasis\n                      <jats:sup>\u00ae<\/jats:sup>\n                      ; Allergan, Irvine, CA) as a comparator. In the repeat-dosing phase, OTX-101 (0.01%, 0.05%, or 0.1% CsA) or comparator was instilled 4 times per day for 7 days. Samples collected included whole blood, tears, and ocular tissues\/fluids (aqueous humor, choroid-retina, conjunctiva, cornea, superior eyelid, third eyelid, iris\/ciliary body, lacrimal gland, lens, sclera, and vitreous humor). CsA concentrations were analyzed using liquid chromatography-tandem mass spectrometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Analysis included samples from 112 rabbits. The highest concentration of CsA following a single OTX-101 0.05% instillation occurred in the third eyelid (C\n                      <jats:sub>max<\/jats:sub>\n                      \u2009=\u20091,200\u2009ng\/g). Concentrations of CsA in the cornea and superior bulbar conjunctiva increased in a dose-related manner following repeated administration of OTX-101 formulations; C\n                      <jats:sub>max<\/jats:sub>\n                      [T\n                      <jats:sub>max<\/jats:sub>\n                      (h)] for cornea was 1,543\u2009ng\/g (6.50), 5,410\u2009ng\/g (7.0), and 8,123\u2009ng\/g (6.50), for 0.01%, 0.05%, and 0.1% CsA concentrations, respectively; for superior bulbar conjunctiva was 726\u2009ng\/g (6.50), 1,468\u2009ng\/g (6.50), and 2,080\u2009ng\/g (6.25), respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>OTX-101 topical ophthalmic instillation resulted in extensive distribution of CsA in ocular tissues, particularly in target tissues for DED (cornea and conjunctiva), while systemic exposure was negligible.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2018.0106","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T11:03:22Z","timestamp":1564398202000},"page":"395-402","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":37,"title":["Ocular Distribution of Cyclosporine Following Topical Administration of OTX-101 in New Zealand White Rabbits"],"prefix":"10.1177","volume":"35","author":[{"given":"Sidney L.","family":"Weiss","sequence":"first","affiliation":[{"name":"Auven Therapeutics, Delray Beach, Florida."},{"name":"i-novion, Inc., Randolph, New Jersey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Kramer Consulting LLC, North Potomac, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,9,5]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2003.10.036"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.9.3686"},{"key":"e_1_3_3_4_2","first-page":"653","article-title":"Effect of cyclosporine on conjunctival mucin in a canine keratoconjunctivitis sicca model","volume":"42","author":"Moore C.P.","year":"2001","unstructured":"Moore C.P., , McHugh J.B., , Thorne J.G., , and Phillips T.E. Effect of cyclosporine on conjunctival mucin in a canine keratoconjunctivitis sicca model. Invest. Ophthalmol. Vis. Sci. 42:653\u2013659, 2001.","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.011"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2012.748052"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-0124(12)70081-2"},{"key":"e_1_3_3_8_2","volume-title":"(cyclosporine ophthalmic emulsion) 0.05%, for topical ophthalmic use. Full prescribing information","author":"Restasis\u00ae","year":"2017","unstructured":"Restasis\u00ae. (cyclosporine ophthalmic emulsion) 0.05%, for topical ophthalmic use. Full prescribing information. 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