{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:47:09Z","timestamp":1782107229655,"version":"3.54.5"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Quizartinib is an oral, potent, selective FMS\u2010like tyrosine kinase 3 (FLT3) inhibitor, approved for the treatment of\n                    <jats:italic>FLT3<\/jats:italic>\n                    \u2010internal tandem duplication (ITD)\u2013positive acute myeloid leukemia (AML) and under investigation in patients with newly diagnosed\n                    <jats:italic>FLT3<\/jats:italic>\n                    \u2010ITD\u2013negative AML. Quizartinib is metabolized by cytochrome P450 3A (CYP3A) in\u00a0vitro, primarily into the active metabolite AC886, a CYP3A substrate. These phase 1, open\u2010label, randomized, parallel\u2010group trials assessed the effect of efavirenz, a moderate CYP3A inducer, and rufinamide, a weak CYP3A inducer, on the pharmacokinetics of quizartinib and AC886, and the safety and tolerability of quizartinib in healthy participants. Each study enrolled 32 participants; 16 received 60\u2009mg quizartinib alone and 16 received 60\u2009mg quizartinib plus either 600\u2009mg efavirenz or 400\u2009mg rufinamide. Coadministration with efavirenz decreased the maximum plasma concentration (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ) and area under the plasma concentration\u2013time curve extrapolated to infinity (AUC\n                    <jats:sub>inf<\/jats:sub>\n                    ) of quizartinib by ~45% and ~90%, respectively, versus quizartinib alone; AC886\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>inf<\/jats:sub>\n                    also decreased by ~68% and ~96%, respectively. Coadministration with rufinamide had modest impact on quizartinib exposure (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>inf<\/jats:sub>\n                    decreased by ~19% and ~34%, respectively, vs. quizartinib alone). Coadministration of rufinamide and quizartinib decreased AC886\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>inf<\/jats:sub>\n                    by ~47% and ~53%, respectively, versus quizartinib alone. Quizartinib was well tolerated and no new safety signals were observed. These results suggest that concomitant use of quizartinib and moderate CYP3A inducers should be avoided. Concomitant use of weak CYP3A inducers does not warrant dose adjustment, since the impact on quizartinib exposure is clinically nonrelevant.\n                  <\/jats:p>","DOI":"10.1111\/cts.70619","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T10:33:04Z","timestamp":1780655584000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Efavirenz and Rufinamide on the Pharmacokinetics and Safety of Quizartinib: Two Phase 1 Studies in Healthy Participants"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5981-2322","authenticated-orcid":false,"given":"YoungJun","family":"Yoo","sequence":"first","affiliation":[{"name":"Daiichi Sankyo Inc.  Basking Ridge New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamim","family":"Zahir","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Inc.  Basking Ridge New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0689-4160","authenticated-orcid":false,"given":"Shinichi","family":"Inaba","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoin","family":"Koo","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Inc.  Basking Ridge New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar","family":"Garimella","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Inc.  Basking Ridge New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malaz","family":"Abutarif","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Inc.  Basking Ridge New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zheng","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Inc.  Basking Ridge New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Kamiyama","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0777-7838","authenticated-orcid":false,"given":"Yuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Inc.  Basking Ridge New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27489"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-242859"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-222034"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121177"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30150-0"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00464-6"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-25-01841"},{"issue":"16","key":"e_1_2_9_9_1","article-title":"QuANTUM\u2010Wild: A Phase 3, Randomized, Double\u2010Blind, Placebo\u2010Controlled Trial of Quizartinib in Combination With Chemotherapy and as Single\u2010Agent Maintenance in FLT3\u2010ITD\u2013Negative Acute Myeloid Leukemia (AML)","volume":"43","author":"Montesinos P.","year":"2025","journal-title":"Journal of Clinical Oncology"},{"key":"e_1_2_9_10_1","unstructured":"\u201cVANFLYTA (Quizartinib) [Prescribing Information] \u201dBasking Ridge NJ: Daiichi Sankyo Inc. 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