{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:10:17Z","timestamp":1784221817758,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T00:00:00Z","timestamp":1573084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Upadacitinib (ABT\u2010494) is a selective Janus kinase (JAK)1 inhibitor being developed for treatment of several inflammatory disorders. A population pharmacokinetic model was developed for upadacitinib using 11,658 plasma concentrations from 1145 subjects from 4 phase 1 and 5 phase 2 studies in healthy subjects and subjects with rheumatoid arthritis, Crohn's disease, ulcerative colitis, or atopic dermatitis. A 2\u2010compartment model with first\u2010order absorption and lag time for the immediate\u2010release formulation and mixed zero\u2010 and first\u2010order absorption with lag time for the extended\u2010release formulation, and linear elimination adequately described upadacitinib plasma concentration\u2013time profiles. The oral bioavailability of upadacitinib extended\u2010release formulation was estimated to be approximately 80% relative to the immediate\u2010release formulation. Covariates included in the final model were creatinine clearance, subject population (healthy subjects vs subjects with atopic dermatitis, ulcerative colitis, or Crohn's disease vs subjects with rheumatoid arthritis) and sex on apparent oral clearance and sex and body weight on apparent volume of distribution of the central compartment. Female subjects had 21% higher upadacitinib steady\u2010state area under the plasma concentration\u2013time curve (AUC) compared to male subjects. Compared to healthy subjects, subjects with atopic dermatitis, ulcerative colitis, or Crohn's disease had 21% higher upadacitinib steady\u2010state AUC, while subjects with rheumatoid arthritis had 35% higher steady\u2010state AUC. Subjects with mild or moderate renal impairment were estimated to have 10% or 22% higher AUC, respectively, compared to subjects with normal renal function. Based on final model parameter estimates, effects of the tested covariates are not expected to result in clinically relevant changes in upadacitinib steady\u2010state exposures.<\/jats:p>","DOI":"10.1002\/jcph.1550","type":"journal-article","created":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T05:39:41Z","timestamp":1573191581000},"page":"528-539","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects With Rheumatoid Arthritis, Crohn's Disease, Ulcerative Colitis, or Atopic Dermatitis: Population Analyses of Phase 1 and 2 Clinical Trials"],"prefix":"10.1002","volume":"60","author":[{"given":"Ahmed","family":"Nader","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Stodtmann","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Deutschland GmbH &amp; Co KG  Ludwigshafen am Rhein Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Friedel","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Deutschland GmbH &amp; Co KG  Ludwigshafen am Rhein Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed\u2010Eslam F.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4937-2775","authenticated-orcid":false,"given":"Ahmed A.","family":"Othman","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,7]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Endotext","author":"Williams CJ","year":"2000"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.12095"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60826-4"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.01.063"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32978"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00754.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02981951"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.03.014"},{"key":"e_1_2_10_10_1","article-title":"A phase 3 randomised, placebo\u2010controlled, double\u2010blind study of upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate: SELECT\u2010MONOTHERAPY","author":"Smolen J","journal-title":"Lancet"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31116-4"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31115-2"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39808"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39801"},{"key":"e_1_2_10_15_1","article-title":"Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double\u2010blind, randomized controlled trial (published online ahead of print July 9, 2019","author":"Fleischmann R","journal-title":"Arthritis Rheumatol"},{"key":"e_1_2_10_16_1","unstructured":"SandbornW GhoshS PanesJ et\u00a0al.Efficacy and safety of upadacitinib as an induction therapy for patients with moderately\u2010to\u2010severely active ulcerative colitis: data from the phase 2b study u\u2010achieve [OP 195]. 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