{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:50:55Z","timestamp":1776819055642,"version":"3.51.2"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,1,7]],"date-time":"2024-01-07T00:00:00Z","timestamp":1704585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tirbanibulin ointment 1% is approved in the United States and Europe for the treatment of actinic keratosis with demonstrated efficacy, safety, and tolerability when applied over a field up to 25\u00a0cm<jats:sup>2<\/jats:sup>. This Phase 1 maximal\u2010use trial determines the plasma pharmacokinetics, safety, and tolerability of tirbanibulin ointment 1% applied to 100\u00a0cm<jats:sup>2<\/jats:sup> of the face or balding scalp in adults with actinic keratosis. Twenty\u2010eight patients self\u2010applied tirbanibulin once daily for a single 5\u2010day treatment course. On Day 5, the mean maximum plasma concentration was 1.06\u00a0ng\/mL and area under the plasma concentration\u2010time curve during a dosing interval was 16.2\u00a0ng\u00a0\u2022\u00a0h\/mL. Systemic exposure was approximately 4\u2010fold higher than in a previous pharmacokinetic study with a 25\u00a0cm<jats:sup>2<\/jats:sup> field, consistent with the increase in the treated area. Tirbanibulin applied to a 100\u2010cm<jats:sup>2<\/jats:sup> treatment field showed favorable safety and tolerability. The most common treatment\u2010emergent adverse events were application site reactions (in 35.7% of patients). All treatment\u2010emergent adverse events and most of the tolerability signs were mild\/moderate and resolved or returned to baseline by Day 29. In summary, under maximal\u2010use conditions, tirbanibulin ointment 1% was safe and well tolerated supporting its potential use over a field up to 100\u00a0cm<jats:sup>2<\/jats:sup>.<\/jats:p>","DOI":"10.1002\/cpdd.1368","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T06:40:20Z","timestamp":1704696020000},"page":"208-218","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Pharmacokinetics, Safety, and Tolerability of a Single 5\u2010Day Treatment of Tirbanibulin Ointment 1% in 100\u00a0cm<sup>2<\/sup>: A Phase 1 Maximal\u2010Use Trial in Patients with Actinic Keratosis"],"prefix":"10.1002","volume":"13","author":[{"given":"Janet","family":"DuBois","sequence":"first","affiliation":[{"name":"DermResearch, Inc. Austin TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry M.","family":"Jones","sequence":"additional","affiliation":[{"name":"J&amp;S Studies, Inc. College Station TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Progressive Clinical Research San Antonio TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meritxell","family":"Falqu\u00e9s","sequence":"additional","affiliation":[{"name":"Almirall  Sant Feliu de Llobregat Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Kiyasova","sequence":"additional","affiliation":[{"name":"Almirall  Sant Feliu de Llobregat Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Almirall  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Otero","sequence":"additional","affiliation":[{"name":"Almirall  Sant Feliu de Llobregat Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep\u2010M.","family":"Jansat","sequence":"additional","affiliation":[{"name":"Almirall  Sant Feliu de Llobregat Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Aubets","sequence":"additional","affiliation":[{"name":"Almirall  Sant Feliu de Llobregat Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rion James","family":"Forconi","sequence":"additional","affiliation":[{"name":"International Clinical Research \u2013 US LLC Sanford FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656560903382622"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14092"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14152"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-018-0348-7"},{"issue":"6","key":"e_1_2_7_6_1","first-page":"294","article-title":"What is the role of field\u2010directed therapy in the treatment of actinic keratosis? Part 2: commonly used field\u2010directed and lesion\u2010directed therapies","volume":"89","author":"Berman B","year":"2012","journal-title":"Cutis"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2011.04432.x"},{"key":"e_1_2_7_8_1","first-page":"35","article-title":"Non\u2010adherence to topical treatments for actinic keratosis","volume":"8","author":"Shergill B","year":"2013","journal-title":"Patient Prefer Adherence"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina55040092"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2016.1178372"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1024"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1041"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ad.2021.07.006"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.010732"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024040"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2021.02.082"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2022.04.013"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-022-00674-3"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-021-01068-9"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.36849\/JDD.2020.5576"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-013-9929-8"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.12833"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/2168479014539157"},{"issue":"12","key":"e_1_2_7_24_1","article-title":"Interventions for actinic keratoses","volume":"12","author":"Gupta AK","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-004-0465-4"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S121323"},{"issue":"7","key":"e_1_2_7_27_1","first-page":"43","article-title":"Actinic keratoses: a comprehensive update","volume":"2","author":"Ibrahim SF","year":"2009","journal-title":"J Clin Aesthet Dermatol"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2011.04005.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.12702"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(99)70114-3"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.2310\/7750.2008.07045"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.07942.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1111170"},{"issue":"2","key":"e_1_2_7_34_1","first-page":"22","article-title":"Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks","volume":"70","author":"Weiss J","year":"2002","journal-title":"Cutis"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1368","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T04:10:14Z","timestamp":1706847014000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,7]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/cpdd.1368"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1368","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,7]]},"assertion":[{"value":"2023-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}