{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T16:50:23Z","timestamp":1793638223505,"version":"4.5.1"},"reference-count":23,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,7,29]],"date-time":"2015-07-29T00:00:00Z","timestamp":1438128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      This therapeutic protein\u2013drug interaction study evaluated the disease\u2010mediated effect of sirukumab (anti\u2010interleukin 6 [anti\u2010IL\u20106] monoclonal antibody) on the pharmacokinetics of the cytochrome P450 (CYP) probe substrates midazolam (CYP3A), omeprazole (CYP2C19), warfarin (CYP2C9), and caffeine (CYP1A2) in patients with active rheumatoid arthritis (RA). Twelve patients with C\u2010reactive protein (CRP)\u2009\u2265\u20098.0\u2009mg\/L at screening received oral administration of a CYP probe cocktail consisting of 0.03\u2009mg\/kg midazolam, 10\u2009mg warfarin\u2009+\u200910\u2009mg vitamin K (equivalent to 5\u2009mg S\u2010warfarin), 20\u2009mg omeprazole, and 100\u2009mg caffeine 1 week before and 1, 3, and 6 weeks after a single subcutaneous dose of 300\u2009mg sirukumab. The results showed that the pharmacokinetics of midazolam, omeprazole, and S\u2010warfarin were nonequivalent before and after the administration of a single dose of 300\u2009mg sirukumab. Area under the plasma concentration\u2013time curve (AUC\n                      <jats:sub>0\u2013<\/jats:sub>\n                      <jats:sub>\u221e<\/jats:sub>\n                      ) for midazolam, omeprazole, and S\u2010warfarin was reduced by 30%\u221235%, 37%\u221245%, and 18%\u221219%, respectively, after sirukumab administration. Caffeine AUC\n                      <jats:sub>0\u2013\u221e<\/jats:sub>\n                      was increased by 20%\u221234% after sirukumab administration. The effect of sirukumab on CYP substrates was sustained for at least 6 weeks. No new adverse drug reactions related to the administration of sirukumab were observed in this study. These results suggest that sirukumab may reverse IL\u20106\u2010mediated suppression of CYP3A, CYP2C9, and CYP2C19 activities in patients with active RA.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcph.561","type":"journal-article","created":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T11:13:57Z","timestamp":1433416437000},"page":"1386-1394","source":"Crossref","is-referenced-by-count":77,"title":["Evaluation of disease\u2010mediated therapeutic protein\u2013drug interactions between an anti\u2013interleukin\u20106 monoclonal antibody (sirukumab) and cytochrome P450 activities in a phase 1 study in patients with rheumatoid arthritis using a cocktail approach"],"prefix":"10.1002","volume":"55","author":[{"given":"Yanli","family":"Zhuang","sequence":"first","affiliation":[{"name":"Janssen Research &amp; Development, LLC Spring House PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dick E.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Janssen Biologics B.V. Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Xu","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Spring House PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Stanley J.","family":"Marciniak","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Spring House PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dion","family":"Chen","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Spring House PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Leon","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Spring House PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh M.","family":"Davis","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Spring House PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Spring House PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","unstructured":"ZhouH MeibohmB. Drug interactions for therapeutic proteins: a journey just beginning. In: Zhou H Meibohm B eds.Drug\u2010Drug Interactions for Therapeutic Biologics. Hoboken NJ: Wiley;2013:1\u20134.","DOI":"10.1002\/9780470571224.pse472"},{"key":"e_1_2_7_3_1","unstructured":"Guidance for Industry DISD Study Design Data Analysis Implications for Dosing and Labeling Recommendations (draft) Center for Drug Evaluation and Research (CDER). February 2012.http:\/\/www.fda.gov\/downloads\/drugs\/guidancecomplianceregulatoryinformation\/guidances\/ucm292362.pdf. 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