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Cytokines, especially interleukin (IL)\u20106, are known suppressors of cytochrome P450 (CYP) enzymes' activity. A physiologically based pharmacokinetic model evaluated the impact of IL\u20106 serum levels on exposure of substrates of various CYP enzymes (1A2, 2C9, 2C19, 3A4, 3A5). Two IL\u20106 kinetics profiles were assessed, the mean IL\u20106 profile with a maximum concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) of IL\u20106 (21\u2009pg\/mL) and the IL\u20106 profile of the patient presenting the highest IL\u20106 <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> (288\u2009pg\/mL) among patients receiving the recommended phase II dose of teclistamab in MajesTEC\u20101. For the mean IL\u20106 kinetics profile, teclistamab was predicted to result in a limited change in exposure of CYP substrates (area under the curve [AUC] mean ratio 0.87\u20131.20). For the maximum IL\u20106 kinetics profile, the impact on omeprazole, simvastatin, midazolam, and cyclosporine exposure was weak to moderate (mean AUC ratios 1.90\u20132.23), and minimal for caffeine and s\u2010warfarin (mean AUC ratios 0.82\u20131.25). Maximum change in exposure for these substrates occurred 3\u20134\u2009days after step\u2010up dosing in cycle 1. These results suggest that after cycle 1, drug interaction from IL\u20106 effect has no meaningful impact on CYP activities, with minimal or moderate impact on CYP substrates. The highest risk of drug interaction is expected to occur during step\u2010up dosing up to 7\u2009days after the first treatment dose (1.5\u2009mg\/kg subcutaneously) and during and after CRS.<\/jats:p>","DOI":"10.1002\/psp4.13144","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T05:51:32Z","timestamp":1717480292000},"page":"1117-1129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluating drug interaction potential from cytokine release syndrome using a physiologically based pharmacokinetic model: A case study of teclistamab"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1974-1170","authenticated-orcid":false,"given":"Marie\u2010Emilie","family":"Willemin","sequence":"first","affiliation":[{"name":"Janssen Research &amp; Development  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun Xin","family":"Wang\u00a0Lin","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; 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