{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T07:03:03Z","timestamp":1770706983671,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,3,17]],"date-time":"2016-03-17T00:00:00Z","timestamp":1458172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Millennium Pharmaceuticals, Cambridge, MA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ixazomib is the first oral proteasome inhibitor to be investigated in the clinic. This clinical study assessed whether the pharmacokinetics of ixazomib would be altered if administered after a high\u2010calorie, high\u2010fat meal. In a 2\u2010period, 2\u2010sequence, crossover study design, adult patients with advanced solid tumors or lymphoma received a 4\u2010mg oral dose of ixazomib as immediate\u2010release capsules on day 1 without food (fasted, administered following an overnight fast) or with food (fed, following consumption of a high\u2010calorie, high\u2010fat meal), followed by another dose on day 15 in the alternate food intake condition (fasted to fed or fed to fasted). Twenty\u2010four patients were enrolled; of these, 15 were included in the pharmacokinetic\u2010evaluable population. Administration of ixazomib after a high\u2010fat meal reduced both the rate and extent of absorption of ixazomib. Under fed conditions, the median time to peak plasma concentration (T<jats:sub>max<\/jats:sub>) of ixazomib was delayed by approximately 3 hours compared with administration in the fasted state (1.02 hours vs 4.0 hours), and there was a 28% reduction in total systemic exposure (area under the curve, AUC) and a 69% reduction in peak plasma concentration (C<jats:sub>max<\/jats:sub>). Together, the results support the administration of ixazomib on an empty stomach, at least 1 hour before or at least 2 hours after food. These recommendations are reflected in the United States Prescribing Information for ixazomib (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link> identifier NCT01454076).<\/jats:p>","DOI":"10.1002\/jcph.719","type":"journal-article","created":{"date-parts":[[2016,2,13]],"date-time":"2016-02-13T15:34:21Z","timestamp":1455377661000},"page":"1288-1295","source":"Crossref","is-referenced-by-count":35,"title":["The Effect of a High\u2010Fat Meal on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma"],"prefix":"10.1002","volume":"56","author":[{"given":"Neeraj","family":"Gupta","sequence":"first","affiliation":[{"name":"Millennium Pharmaceuticals  Cambridge MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Hanley","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals  Cambridge MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karthik","family":"Venkatakrishnan","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals  Cambridge MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals  Cambridge MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunil","family":"Sharma","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute University of Utah  Salt Lake City UT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Bessudo","sequence":"additional","affiliation":[{"name":"California Cancer Associates for Research and Excellence  San Diego CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai\u2010Min","family":"Hui","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals  Cambridge MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Nemunaitis","sequence":"additional","affiliation":[{"name":"Mary Crowley Cancer Research Center  Dallas TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-2766"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0476"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0636"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-548941"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-548826"},{"issue":"21","key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1182\/blood.V124.21.3450.3450","article-title":"Long\u2010term outcome of a phase 1 study of the investigational oral proteasome inhibitor (PI) ixazomib at the recommended phase 3 dose (RP3D) in patients (Pts) with relapsed or refractory systemic light\u2010chain (AL) amyloidosis (RRAL)","volume":"124","author":"Merlini G","year":"2014","journal-title":"Blood"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2014.71"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-015-0230-x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12542"},{"key":"e_1_2_8_11_1","unstructured":"United States Food & Drug Administration. 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