{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:59:46Z","timestamp":1780527586686,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T00:00:00Z","timestamp":1543536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"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":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Upadacitinib is a novel selective oral Janus kinase 1 (JAK) inhibitor being developed for treatment of several inflammatory diseases. Oral contraceptives are anticipated to be a common concomitant medication in the target patient populations. This study was designed to evaluate the effect of multiple doses of upadacitinib on the pharmacokinetics of ethinylestradiol and levonorgestrel in healthy female subjects. This phase I, single\u2010center, open\u2010label, 2\u2010period crossover study evaluated the effect of multiple doses of 30\u00a0mg once daily extended\u2010release upadacitinib on the pharmacokinetics of a single oral dose of ethinylestradiol\/levonorgestrel (0.03\/0.15\u00a0mg; administered alone in period 1 and on day 12 of a 14\u2010day regimen of upadacitinib in period 2) in 22 healthy female subjects. The ratios (90% confidence intervals) for maximum plasma concentration and area under the plasma drug concentration\u2013time curve from time zero to infinity following administration of ethinylestradiol\/levonorgestrel with upadacitinib compared with administration of ethinylestradiol\/ levonorgestrel alone were 0.96 (0.89\u20131.02) and 1.1 (1.04\u20131.19), respectively, for ethinylestradiol, and 0.96 (0.87\u20131.06) and 0.96 (0.85\u20131.07), respectively, for levonorgestrel. The harmonic mean terminal half\u2010life for ethinylestradiol (7.7 vs 7.0\u00a0hours) and levonorgestrel (37.1 vs 33.1\u00a0hours) was similar in the presence and absence of upadacitinib. Ethinylestradiol and levonorgestrel were bioequivalent in the presence and absence of upadacitinib. Therefore, upadacitinib can be administered concomitantly with oral contraceptives containing ethinylestradiol or levonorgestrel.<\/jats:p>","DOI":"10.1002\/jcph.1350","type":"journal-article","created":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T14:22:41Z","timestamp":1543587761000},"page":"510-516","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The JAK1 Inhibitor Upadacitinib Has No Effect on the Pharmacokinetics of Levonorgestrel and Ethinylestradiol: A Study in Healthy Female Subjects"],"prefix":"10.1002","volume":"59","author":[{"given":"Mohamed\u2010Eslam F.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics  AbbVie, North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheryl","family":"Trueman","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics  AbbVie, North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Feng","sequence":"additional","affiliation":[{"name":"Data and Statistical Sciences  AbbVie, North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Friedman","sequence":"additional","affiliation":[{"name":"Immunology Development AbbVie  North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Othman","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics  AbbVie, North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41927-018-0031-x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80505-1"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.5.2623"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07128.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R700016200"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22033"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2011.02.003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X12470753"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2014.918604"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39808"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39801"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(17)34357-3"},{"key":"e_1_2_10_14_1","unstructured":"AbbVie.A multicenter randomized double\u2010blind placebo\u2010controlled study of ABT\u2010494 for the induction of symptomatic and endoscopic remission in subjects with moderately to severely active Crohn's disease who have inadequately responded to or are intolerant to anti\u2010TNF therapy (Celest Study) [ClinicalTrials.gov identifier NCT02365649].https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02365649?term=NCT02365649&rank=1. Accessed January 3 2018."},{"key":"e_1_2_10_15_1","unstructured":"AbbVie.A phase 3 study to compare ABT\u2010494 to abatacept in subjects with rheumatoid arthritis on stable dose of conventional synthetic disease\u2010modifying antirheumatic drugs (csDMARDs) who have an inadequate response or intolerance to biologic DMARDs (SELECT\u2010CHOICE) [ClinicalTrials.gov Identifier NCT03086343].https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03086343?term=NCT03086343&rank=1. Accessed January 3 2018."},{"key":"e_1_2_10_16_1","unstructured":"AbbVie.A study comparing ABT\u2010494 monotherapy to methotrexate (MTX) monotherapy in subjects with rheumatoid arthritis (RA) who have an inadequate response to MTX (SELECT\u2010MONOTHERAPY) [ClinicalTrials.gov identifier NCT02706951].https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02706951?term=NCT02706951&rank=1. Accessed January 3 2018."},{"key":"e_1_2_10_17_1","unstructured":"AbbVie.A study comparing ABT\u2010494 to placebo and to adalimumab in participants with psoriatic arthritis who have an inadequate response to at least one non\u2010biologic disease modifying anti\u2010rheumatic drug (SELECT \u2010 PsA 1) [ClinicalTrials.gov identifier NCT03104400].https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03104400?term=NCT03104400&rank=1. Accessed January 3 2018."},{"key":"e_1_2_10_18_1","unstructured":"Guttman\u2010YasskyE SilverbergJI ThaciD HongC\u2010H MohamedM\u2010E OthmanAA.Primary results from a phase 2b randomized placebo\u2010controlled trial of upadacitinib for patients with atopic dermatitis [abstract 6533]. In: American Academy of Dermatology Annual Meeting San Diego CA;February2018:16\u201320."},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31116-4"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31115-2"},{"key":"e_1_2_10_21_1","unstructured":"AbbVie.A study comparing ABT\u2010494 to placebo in participants with active psoriatic arthritis who have a history of inadequate response to at least one biologic disease modifying anti\u2010rheumatic drug (SELECT \u2010 PsA 2) [ClinicalTrials.gov identifier NCT03104374].https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03104374?term=NCT03104374&rank=1. Accessed January 3 2018."},{"key":"e_1_2_10_22_1","unstructured":"AbbVie.A study to evaluate ABT\u2010494 in adult subjects with moderate to severe atopic dermatitis [ClinicalTrials.gov identifier NCT02925117].https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02925117?term=NCT02925117&rank=1. Accessed January 3 2018."},{"key":"e_1_2_10_23_1","unstructured":"AbbVie.A study to evaluate the safety and efficacy of ABT\u2010494 for induction and maintenance therapy in subjects with moderately to severely active ulcerative colitis [ClinicalTrials.gov identifier NCT02819635].https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02819635?term=NCT02819635&rank=1. Accessed January 3 2018."},{"key":"e_1_2_10_24_1","unstructured":"Abbvie.A multicenter randomized double\u2010blind placebo\u2010controlled study evaluating the safety and efficacy of upadacitinib in subjects with active ankylosing spondylitis (SELECT Axis 1). [ClinicalTrials.gov identifier NCT03178487].https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03178487?term=NCT03178487&rank=1. Accessed April 9 2018."},{"key":"e_1_2_10_25_1","article-title":"Pharmacokinetics of upadacitinib with the clinical regimens of the extended\u2010release formulation utilized in rheumatoid arthritis phase 3 trials [published online ahead of print April 24, 2018]","author":"Mohamed MF","journal-title":"Clin Pharmacol Drug Dev"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0605-6"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13329"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4755-10-7"},{"issue":"3","key":"e_1_2_10_29_1","first-page":"63","article-title":"What types of birth control are available","volume":"21","author":"Dunaway A","year":"2008","journal-title":"JAAPA"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200746020-00003"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/102184"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02917.x"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(99)70138-4"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2015.03.006"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.270"},{"key":"e_1_2_10_36_1","unstructured":"United States Food and Drug Administration.Guidance for industry: drug interaction studies \u2010 study design data analysis implications for dosing and labeling recommendations.2012.https:\/\/www.xenotech.com\/regulatory-documents\/2012\/2012_guidance.aspx. Accessed 16 November 2018."},{"issue":"29","key":"e_1_2_10_37_1","first-page":"1","article-title":"Use of contraception in the United States: 1982\u20132008","author":"Mosher WD","year":"2010","journal-title":"Vital Health Stat 23"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-013-9470-x"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2008.03120.x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1285"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.1350","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1350","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T18:50:54Z","timestamp":1694717454000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1350"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,30]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1002\/jcph.1350"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1350","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,30]]},"assertion":[{"value":"2018-09-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}