{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:49:04Z","timestamp":1760028544878,"version":"3.37.3"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,4,20]],"date-time":"2020-04-20T00:00:00Z","timestamp":1587340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This phase 1 open\u2010label, multicenter, 3\u2010period, fixed\u2010sequence study evaluated the effect of multiple doses of vemurafenib on the pharmacokinetics of 1 dose of tizanidine, a probe CYP1A2 substrate, in patients with <jats:italic>BRAF<\/jats:italic><jats:sup>V600<\/jats:sup> mutation\u2013positive metastatic malignancy. Patients received 1 dose of tizanidine 2 mg on day 1 (period A), vemurafenib 960 mg twice daily on days 2\u201021 (period B), and 1 dose of tizanidine 2 mg and vemurafenib 960 mg twice daily on day 22 (period C). Log\u2010transformed area under the concentration\u2010time curve (AUC) and maximum plasma concentration (C<jats:sub>max<\/jats:sub>) values for tizanidine in 16 patients were compared between periods A (tizanidine alone) and C (tizanidine plus vemurafenib) using an analysis of variance model. Multiple doses of vemurafenib increased plasma exposure of 1 dose of tizanidine, with geometric mean ratios (period C\/period A) for C<jats:sub>max<\/jats:sub>, AUC<jats:sub>inf<\/jats:sub>, and AUC<jats:sub>last<\/jats:sub> of 2.15 (90%CI, 1.71\u20102.71), 4.22 (90%CI, 3.37\u20105.28), and 4.74 (90%CI, 3.55\u20106.33), respectively; 90%CIs were all outside predefined limits for lack of drug\u2010drug interaction (0.82\u20101.22). This study confirmed vemurafenib as a moderate inhibitor of CYP1A2 in vivo, with a statistically significant drug\u2010drug interaction with tizanidine. Caution should be exercised when dosing vemurafenib concurrently with CYP1A2 substrates.<\/jats:p>","DOI":"10.1002\/cpdd.788","type":"journal-article","created":{"date-parts":[[2020,4,20]],"date-time":"2020-04-20T19:49:05Z","timestamp":1587412145000},"page":"651-658","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine (a CYP1A2 Substrate) in Patients With <i>BRAF<\/i><sup>V600<\/sup> Mutation\u2013Positive Malignancies"],"prefix":"10.1002","volume":"9","author":[{"given":"Weijiang","family":"Zhang","sequence":"first","affiliation":[{"name":"F. Hoffmann\u2010La Roche Ltd.  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"McIntyre","sequence":"additional","affiliation":[{"name":"pRED Roche Innovation Centre Welwyn Roche Products Ltd.  Welwyn Garden City UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd","family":"Riehl","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harper","family":"Forbes","sequence":"additional","affiliation":[{"name":"F. Hoffmann\u2010La Roche Ltd.  Mississauga Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enric","family":"Bertran","sequence":"additional","affiliation":[{"name":"pRED Roche Innovation Centre Basel Roche Products Ltd.  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Jin","family":"Choi","sequence":"additional","affiliation":[{"name":"Severance Hospital Yonsei University Health System  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dae Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeeyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70012-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408868"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30122-X"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.5029"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-013-2324-5"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.255"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0523-7"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.643"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1111"},{"issue":"7","key":"e_1_2_8_12_1","doi-asserted-by":"crossref","DOI":"10.3390\/molecules22071143","article-title":"Review of ligand specificity factors for CYP1A subfamily enzymes from molecular modeling studies reported to\u2010date","volume":"22","author":"Sridhar J","year":"2017","journal-title":"Molecules"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602530903286476"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-009-9127-y"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2003.02028.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2003.12.005"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.08.018"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009341961"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2006.02653.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-007-0389-y"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2005.05.012"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112302"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpdd.788","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.788","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.788","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.788","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:01:54Z","timestamp":1693958514000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.788"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,20]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1002\/cpdd.788"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.788","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"type":"print","value":"2160-763X"},{"type":"electronic","value":"2160-7648"}],"subject":[],"published":{"date-parts":[[2020,4,20]]},"assertion":[{"value":"2019-12-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}