{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T01:06:28Z","timestamp":1788051988285,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T00:00:00Z","timestamp":1564963200000},"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":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of this study was to characterize the effects of upadacitinib, a Janus kinase 1 inhibitor, on in vivo activity of different cytochrome P450 (CYP) enzymes using a cocktail approach. Healthy subjects (n = 20) received single oral doses of the modified Cooperstown 5+1 cocktail drugs (midazolam [CYP3A], caffeine [CYP1A2], warfarin + vitamin K [CYP2C9], omeprazole [CYP2C19], and dextromethorphan [CYP2D6]) without upadacitinib and on day 11 (midazolam) or 12 (all other probes) of a 15\u2010day regimen of upadacitinib 30 mg once daily (extended\u2010release formulation). Serial blood samples and 12\u2010hour urine samples were collected for assays of the probe substrates and select metabolites. The ratio (90%CI) of area under the plasma concentration\u2010time curve from time 0 to infinity (AUC<jats:sub>inf<\/jats:sub>) central values when the cocktail drugs were administered with upadacitinib relative to when administered alone were 0.74 (0.68\u20100.80) for midazolam, 1.22 (1.15\u20101.29) for caffeine, 1.11 (1.07\u20101.15) for S\u2010warfarin, 1.07 (0.95\u20101.22) for dextromethorphan, and 0.82 (0.72\u20100.94) for omeprazole. The ratio (90%CI) was 1.09 (1.00\u20101.19) for 5\u2010hydroxy\u2010omeprazole to omeprazole AUC<jats:sub>inf<\/jats:sub> ratio and 1.17 (0.97\u20101.41) for dextromethorphan to dextrorphan 12\u2010hour molar urinary ratio. Upadacitinib 30 mg once daily (a dose that is twice the optimal dose in rheumatoid arthritis based on phase 3 results) has a limited effect on CYP3A activity (26% decrease in exposure of midazolam, a sensitive CYP3A substrate) and no relevant effects on CYP1A2, CYP2C9, CYP2C19, or CYP2D6 activity in vivo. No clinically relevant changes in plasma exposures are expected for drugs that are substrates for the evaluated CYP enzymes when coadministered with upadacitinib.<\/jats:p>","DOI":"10.1002\/jcph.1496","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T07:58:44Z","timestamp":1564991924000},"page":"86-95","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Effects of Upadacitinib Coadministration on the Pharmacokinetics of Sensitive Cytochrome P450 Probe Substrates: A Study With the Modified Cooperstown 5+1 Cocktail"],"prefix":"10.1002","volume":"60","author":[{"given":"Mohamed\u2010Eslam F.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Statistics AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey V.","family":"Enejosa","sequence":"additional","affiliation":[{"name":"Immunology Development AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ogert","family":"Fisniku","sequence":"additional","affiliation":[{"name":"Regulated Bioanalysis 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.  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