{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:25:02Z","timestamp":1760549102152},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":279,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:p>Brivanib alaninate is the orally available prodrug of brivanib, a dual inhibitor of fibroblast growth factor and vascular endothelial growth factor signaling pathways that is under therapeutic investigation for various malignancies. Brivanib alaninate inhibits CYP3A4 in vitro, and thus there is potential for drug\u2010drug interaction with CYP3A4 substrates, such as midazolam. The present study evaluated pharmacokinetic parameters and safety\/tolerability upon coadministration of brivanib alaninate and midazolam. Healthy participants received intravenous (IV) or oral midazolam with and without oral brivanib alaninate. Blood samples for pharmacokinetic analysis were collected up to 12 hours after midazolam and up to 48 hours after brivanib alaninate. Twenty\u2010four participants were administered study drugs; 21 completed the trial. No clinically relevant effect of brivanib alaninate on the overall exposure to midazolam following IV or oral administration was observed. Orally administered brivanib alaninate was generally well tolerated in the presence of IV or oral midazolam. The lack of a pharmacokinetic interaction between brivanib and midazolam indicates that brivanib alaninate does not influence either intestinal or hepatic CYP3A4 and confirms that brivanib alaninate may be safely coadministered with midazolam and other CYP3A4 substrates.<\/jats:p>","DOI":"10.1177\/0091270011407495","type":"journal-article","created":{"date-parts":[[2011,6,10]],"date-time":"2011-06-10T08:59:19Z","timestamp":1307696359000},"page":"914-921","source":"Crossref","is-referenced-by-count":5,"title":["Lack of Effect of Brivanib on the Pharmacokinetics of Midazolam, a CYP3A4 Substrate, Administered Intravenously and Orally in Healthy Participants"],"prefix":"10.1002","volume":"52","author":[{"given":"Shariq","family":"Syed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela L.","family":"Clemens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deanne","family":"Lathers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Kollia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arindam","family":"Dhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Walters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Masson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/35025220"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-2427"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060655"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0708857"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa065044"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2442"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64325-8"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.09.005"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/156800909789057006"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2780"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.11.021"},{"key":"e_1_2_5_13_2","unstructured":"KopetzS HoffPM EngC et al.Levels of angiogenic cytokines prior to disease progression in metastatic colorectal cancer patients treated with bevacizumab. 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