{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:20:04Z","timestamp":1787498404352,"version":"build-2736575974"},"reference-count":43,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21H04203"],"award-info":[{"award-number":["JP21H04203"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008728","name":"Japan Research Foundation for Clinical Pharmacology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008728","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Biochem"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tocilizumab co-administration and inflammatory conditions potentially alter the activity of cytochrome P450 (CYP) 3A4 by modulating the interleukin-6 (IL-6) signaling pathway in patients with rheumatoid arthritis (RA). This study aimed to evaluate the correlations of serum levels of tocilizumab with IL-6 and CYP3A activity in RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>RA patients (n = 35) with controllable disease activity using intravenous or subcutaneous tocilizumab were enrolled. Serum tocilizumab was monitored at the trough point after reaching steady-state. Serum levels of IL-6, its soluble receptor (sIL-6R), 4\u03b2-hydroxycholesterol (4\u03b2-OHC), and 25-hydroxyvitamin D (25-OHD) and CYP3A5 genotype were determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The RA patients had a wide variation of serum tocilizumab level (interquartile range, 9.8\u201324.6\u00a0\u00b5g\/mL). Tocilizumab treatment led to abnormally high levels of serum IL-6 and sIL-6R. The serum level of tocilizumab was correlated with that of IL-6 but not sIL-6R. In the tocilizumab-treated RA patients, the median serum levels of 4\u03b2-OHC and 25-OHD were 36.7 and 17.7\u00a0ng\/mL, respectively, and no correlations with the serum level of tocilizumab were observed. CYP3A5 genetic polymorphisms were not also associated with the serum level of 4\u03b2-OHC. RA patients with the\n                      <jats:italic toggle=\"yes\">CYP3A5*1<\/jats:italic>\n                      allele exhibited a correlation between serum levels of tocilizumab and 4\u03b2-OHC, while those with\n                      <jats:italic toggle=\"yes\">CYP3A5*3\/*3<\/jats:italic>\n                      did not.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tocilizumab treatment raised the serum IL-6 level in a concentration-dependent manner. In the RA patients with functional CYP3A5 protein, the serum tocilizumab level partially explained the interindividual variation in CYP3A activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/00045632251357148","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T21:45:57Z","timestamp":1750887957000},"page":"49-57","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Relationships of serum levels of tocilizumab to interleukin-6 and endogenous markers of CYP3A activity in patients with rheumatoid arthritis"],"prefix":"10.1177","volume":"63","author":[{"given":"Takashi","family":"Mochizuki","sequence":"first","affiliation":[{"name":"Hamamatsu University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaito","family":"Shibata","sequence":"additional","affiliation":[{"name":"Hamamatsu University School of Medicine"},{"name":"Shinshu University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7447-3789","authenticated-orcid":false,"given":"Takafumi","family":"Naito","sequence":"additional","affiliation":[{"name":"Hamamatsu University School of Medicine"},{"name":"Shinshu University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Shimoyama","sequence":"additional","affiliation":[{"name":"Hamamatsu University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyoshi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Hamamatsu University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Hamamatsu University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2003.01778.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-018-0219-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.35"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.bor.0000218949.19860.d1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2014.938325"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2005.05.010"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-155846"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2008.07.002"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/138920007779815986"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.561"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0462-8"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13355"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2024.101027"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12431"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.51.5.741"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2019.05.003"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e3282f50ee9"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2016.04.001"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2018.12.007"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.338"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2022.08.003"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12976"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22110"},{"issue":"10","key":"e_1_3_3_25_2","first-page":"S467","article-title":"Optimal dose prediction by pharmacokinetic and biomarker response of subcutaneous tocilizumab treatment a Phase I\/II study evaluating the safety, pharmacokinetics and clinical response in patients with rheumatoid arthritis","volume":"62","author":"Ohta S","year":"2010","unstructured":"Ohta S, Tsuru T, Terao K, et al. 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