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Treatment with anti\u2010IL\u20106 therapy can reverse the IL\u20106\u2010mediated downregulation of CYP enzymes, resulting in changes in plasma levels of CYP substrates. The primary objective of this study was to evaluate the impact of the IL\u20106 inhibitor olokizumab on the pharmacokinetics of CYP probe substrates in subjects with active RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seventeen patients with active RA were orally administered a phenotyping cocktail of midazolam (CYP3A4 substrate), omeprazole (CYP2C19 substrate), warfarin (CYP2C9 substrate) and caffeine (CYP1A2 substrate) alone and 2\u00a0weeks after a single subcutaneous injection of 128\u2009mg olokizumab. The pharmacokinetic parameters of each substrate were calculated using noncompartmental analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixteen of 17 enrolled patients received the complete doses of the cocktail drugs and olokizumab and were eligible for the pharmacokinetic evaluations. After single\u2010dose administration of olokizumab, the exposure of midazolam and omeprazole decreased by 30\u201033% and 26\u201032%, respectively, compared to when the substrates were administered along via cocktail. In the presence of olokizumab, caffeine exposure increased by 19\u201023% compared to caffeine administration alone. There were no significant changes in S\u2010warfarin exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with active RA, olokizumab potentially reverses the IL\u20106\u2010mediated suppression of CYP3A4 and CYP2C19. According to FDA guidance, olokizumab is considered a weak inducer of CYP3A4 and CYP2C19.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16175","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T12:04:30Z","timestamp":1720613070000},"page":"2811-2822","source":"Crossref","is-referenced-by-count":4,"title":["Inflammation\u2010mediated drug interactions of olokizumab and cytochrome P450 activities in patients with rheumatoid arthritis"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2569-7188","authenticated-orcid":false,"given":"Svetlana","family":"Agachi","sequence":"first","affiliation":[{"name":"Discipline of Rheumatology and Nephrology, Department of Internal Medicine Nicolae Testemi\u021banu State University of Medicine and Pharmacy  Chi\u0219in\u0103u Republic of Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9206-0398","authenticated-orcid":false,"given":"Marina","family":"Beloukhova","sequence":"additional","affiliation":[{"name":"R\u2010Pharm Group  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Mould","sequence":"additional","affiliation":[{"name":"Projections Research Inc.  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