{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:01:58Z","timestamp":1782975718408,"version":"3.54.5"},"reference-count":11,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"\n Objective<\/jats:title>\n To evaluate the effects of mild and moderate hepatic impairment on the pharmacokinetics and safety of SHR0302.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This open-label, parallel-group study enrolled 24 Chinese subjects, including subjects with normal hepatic function and those with mild or moderate hepatic impairment (8 per group). All subjects received a single oral dose of SHR0302 (8\u00a0mg). Plasma PK parameters of SHR0302 and its metabolite, SHR161279, were assessed and compared across groups. Safety was evaluated throughout the study.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Mild hepatic impairment had minimal effect on the exposure of SHR0302. In subjects with moderate hepatic impairment, the C\n max<\/jats:sub>\n of SHR0302 was approximately 17% lower than that in subjects with normal hepatic function, whereas AUC\n 0-t<\/jats:sub>\n and\n \n \n \n \n AUC<\/mml:mtext>\n \n 0<\/mml:mn>\n \u2010<\/mml:mo>\n \u221e<\/mml:mi>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n remained generally unchanged. Meanwhile, exposure to SHR161279 decreased in both hepatic impairment groups, with reductions of approximately 21%\u201338%. SHR0302 was generally safe after single-dose administration. Eight subjects (8\/24, 33.3%) experienced treatment-emergent adverse events (TEAEs). No serious adverse events were reported.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Mild and moderate hepatic impairment had minimal effect on SHR0302 exposure. Based on the single-dose pharmacokinetic and safety data, dose adjustment of SHR0302 may not be necessary in patients with mild or moderate hepatic impairment.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n https:\/\/clinicaltrials.gov\/<\/jats:ext-link>\n , identifier NCT04293029.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2026.1857187","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:35:25Z","timestamp":1782970525000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and safety of SHR0302, a selective JAK1 inhibitor, in Chinese patients with hepatic impairment"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiajia","family":"Mai","sequence":"first","affiliation":[{"name":"Department of Phase I Clinical Trial Unit, The First Hospital of Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongda","family":"Lin","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Jiangsu Hengrui Pharmaceuticals Co., Ltd.","place":["Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Phase I Clinical Trial Unit, The First Hospital of Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Phase I Clinical Trial Unit, The First Hospital of Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Phase I Clinical Trial Unit, The First Hospital of Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglong","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Chen","sequence":"additional","affiliation":[{"name":"Abdominal Ultrasound Department, The First Hospital of Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"B1","volume-title":"RINVOQ\u00ae (Upadacitinib) extended-release Tablets, for Oral Use: Prescribing Information","year":"2026"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1126\/science.277.5332.1630","article-title":"STATs and gene regulation","volume":"277","author":"Darnell","year":"1997","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1126\/science.abn8933","article-title":"Structure of a janus kinase cytokine receptor complex reveals the basis for dimeric activation","volume":"376","author":"Glassman","year":"2022","journal-title":"Science"},{"key":"B4","volume-title":"Pfizer Inc. CIBINQO\u00ae (Abrocitinib) Tablets, for Oral Use: Prescribing Information","year":"2023"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1056\/nejmoa1606910","article-title":"Tofacitinib as induction and maintenance therapy for ulcerative colitis","volume":"376","author":"Sandborn","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.semcdb.2008.08.010","article-title":"Inteferons pen the JAK\u2013STAT pathway","volume":"19","author":"Schindler","year":"2008","journal-title":"Semin. Cell Dev. Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1001\/jamadermatol.2020.1406","article-title":"Efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis","volume":"156","author":"Silverberg","year":"2020","journal-title":"JAMA Dermatol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"ii3","DOI":"10.1093\/rheumatology\/keab024","article-title":"JAK1: number one in the family; number one in inflammation?","volume":"60","author":"Spinelli","year":"2021","journal-title":"Rheumatology"},{"key":"B9","volume-title":"Guidance for IndustryPharmacokinetics in Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling","year":"2003"},{"key":"B10","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1056\/nejmoa1112072","article-title":"Tofacitinib or adalimumab versus placebo in rheumatoid arthritis","volume":"367","author":"van Vollenhoven","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/gb-2004-5-12-253","article-title":"The janus kinases (jaks)","volume":"5","author":"Yamaoka","year":"2004","journal-title":"Genome Biol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1857187\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:35:27Z","timestamp":1782970527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1857187\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":11,"alternative-id":["10.3389\/fphar.2026.1857187"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1857187","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"article-number":"1857187"}}