{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:12:05Z","timestamp":1789996325653,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003661","name":"Korea Institute for Advancement of Technology","doi-asserted-by":"publisher","award":["RS\u20102024\u201000434342"],"award-info":[{"award-number":["RS\u20102024\u201000434342"]}],"id":[{"id":"10.13039\/501100003661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009950","name":"Ministry of Education","doi-asserted-by":"publisher","award":["RS\u20102025\u201025397599"],"award-info":[{"award-number":["RS\u20102025\u201025397599"]}],"id":[{"id":"10.13039\/100009950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Wet age\u2010related macular degeneration (wAMD) is a leading cause of vision loss, and human dose selection for ocular therapeutics remains a key translational challenge. We developed a physiologically based pharmacokinetic (PBPK) model for EB\u2010203 to guide dose selection by translating preclinical ocular tissue exposure to human. PK data were obtained from mouse and rabbit studies and human plasma PK from a phase I trial. The model incorporated species\u2010specific ocular physiology, drug permeability, and pharmacokinetics, and was implemented using an open\u2010source PBPK modeling software (MoBi, version 12.2, Open Systems Pharmacology). Drug\u2010specific model parameters were estimated using mouse and rabbit plasma and ocular tissue concentration data. Human plasma PK data from a Phase I clinical trial were then used to estimate human\u2010specific systemic clearance, and human ocular tissue concentrations were subsequently predicted by the model. Simulated human retinal drug concentrations (AUC,\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    , and\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>avr<\/jats:sub>\n                    ) under multiple dosing regimens were evaluated against preclinical efficacy thresholds to determine the optimal dosing strategy. The model adequately described drug disposition across species, with most predicted PK parameters falling within a 2\u2010fold error of the observed data. Simulations suggested that a 4% four\u2010times\u2010daily dosing regimen in humans achieves retinal exposure comparable to the efficacious mouse concentrations. No significant systemic accumulation was observed, indicating a favorable safety profile. This PBPK framework provides a practical approach for predicting human ocular drug exposure and can be adapted to other compounds or ocular indications in the absence of direct tissue sampling. These results support further clinical evaluation of EB\u2010203 for the treatment of wAMD.\n                  <\/jats:p>","DOI":"10.1111\/cts.70717","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:23:19Z","timestamp":1788495799000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Determination of Human Effective Dose via Translational Ocular Modeling: Clinical Translation of a Novel Topical Agent Using\n                    <scp>PBPK<\/scp>"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-597X","authenticated-orcid":false,"given":"Woojin","family":"Jung","sequence":"first","affiliation":[{"name":"Graduate School of Clinical Pharmacy CHA University  Pocheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie Jaeheung","family":"Lee","sequence":"additional","affiliation":[{"name":"EyeBioKorea Inc.  Busan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunseok","family":"Cho","sequence":"additional","affiliation":[{"name":"EyeBioKorea Inc.  Busan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung Ah","family":"Min","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research Inje University  Gimhae\u2010si Gyeongsangnam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8793-2449","authenticated-orcid":false,"given":"Hwi\u2010yeol","family":"Yun","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungnam National University  Daejeon Republic of Korea"},{"name":"Senior Health Convergence Research Center Chungnam National University  Daejeon Republic of Korea"},{"name":"Department of Bio\u2010AI Convergence Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5799-4489","authenticated-orcid":false,"given":"Soyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4121-9757","authenticated-orcid":false,"given":"Jaewook","family":"Yang","sequence":"additional","affiliation":[{"name":"EyeBioKorea Inc.  Busan Republic of Korea"},{"name":"Department of Ophthalmology Inje University Busan Paik Hospital  Busan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6026-7063","authenticated-orcid":false,"given":"Jung\u2010woo","family":"Chae","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungnam National University  Daejeon Republic of Korea"},{"name":"Senior Health Convergence Research Center Chungnam National University  Daejeon Republic of Korea"},{"name":"Department of Bio\u2010AI Convergence Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","unstructured":"N.Galloway W.Amoaku andP.Galloway Common Eye Diseases and Their Management \u201d (1999 https:\/\/link.springer.com\/content\/pdf\/10.1007\/978\u20103\u2010319\u201032869\u20100.pdf.","DOI":"10.1007\/978-1-4471-3625-5_1"},{"key":"e_1_2_11_3_1","volume-title":"Global Initiative for the Elimination of Avoidable Blindness: Action Plan 2006\u20132011","author":"World Health Organization","year":"2007"},{"key":"e_1_2_11_4_1","unstructured":"National Institute for Health and Care Excellence \u201cAge\u2010Related Macular Degeneration: Diagnosis and Management \u201d (2018)."},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495\u2010200767080\u201000007\/METRICS"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2006.10.004"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.OPHTHA.2012.09.006"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/EYE.2011.66"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.ADDR.2006.07.027"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/PSP.2013.41"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS242316661"},{"key":"e_1_2_11_12_1","unstructured":"D.Williams Rabbit and Rodent Ophthalmology \u201d (2007 https:\/\/www.researchgate.net\/publication\/236623251."},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPS.20217"},{"key":"e_1_2_11_14_1","first-page":"43","volume-title":"Tested Studies for Laboratory Teaching","author":"Goldman C. 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