{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:07:24Z","timestamp":1784549244011,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    E7386, an orally active protein\u2010protein interaction inhibitor, is reported to impair the interaction between transcriptional co\u2010activator CREB\u2010binding protein and \u03b2\u2010catenin. A competent study design exploring the concomitant dosing routes, sensitive intravenous (IV; [\n                    <jats:sup>14<\/jats:sup>\n                    C]) microtracer technology, and oral [\n                    <jats:sup>14<\/jats:sup>\n                    C] radiolabeled dosing was successfully implemented to determine the absolute bioavailability and the absorption, metabolism, and excretion (AME) properties of E7386 in healthy adult participants. In Part 1, 7 participants received a single 40 mg immediate release (IR) tablet of E7386 followed by an IV infusion containing a microtracer solution of\n                    <jats:sup>14<\/jats:sup>\n                    C\u2010labeled E7386 ([\n                    <jats:sup>14<\/jats:sup>\n                    C]E7386; 100 \u00b5g). In Part 2, 8 participants received a single 40 mg powder\u2010in\u2010capsule oral administration of radiolabeled [\n                    <jats:sup>14<\/jats:sup>\n                    C]E7386 (80 \u00b5Ci). The radiolabeled IV [\n                    <jats:sup>14<\/jats:sup>\n                    C] microtracer arm assessed the absorption, absolute oral bioavailability (F), and first\u2010pass effect of E7386. The geometric mean (CV%) absolute bioavailability of E7386 was found to be 23.6% (34.6), which may be attributed to the insufficient absorption, extensive first\u2010pass and rapid systemic metabolism of E7386. The mean (SD) cumulative recovery of\n                    <jats:sup>14<\/jats:sup>\n                    C total radioactivity was 87.9% (6.56) after collection of excreta for up to a maximum of 480 hours postdose. Of the total administered dose, 85.1% was recovered in feces, 0.371% in toilet tissue, and 2.36% in urine. These results suggest that [\n                    <jats:sup>14<\/jats:sup>\n                    C]E7386\u2010related material is predominantly excreted in feces after oral administration. Overall, IV administration and oral administration of a single E7386 dose was tolerable in healthy participants, and adverse events were manageable.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70202","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T08:26:53Z","timestamp":1778747213000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phase 1 Oral Mass Balance and Combined Intravenous [\n                    <sup>14<\/sup>\n                    C] Microtracer Study to Characterize the Absorption, Metabolism, Excretion, and Pharmacokinetics of Antitumor Drug E7386 in Humans"],"prefix":"10.1002","volume":"66","author":[{"given":"Shriram M.","family":"Pathak","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Science Eisai Ltd.  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Hayata","sequence":"additional","affiliation":[{"name":"Deep Human Biology Learning Eisai Co., Ltd  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ueno","sequence":"additional","affiliation":[{"name":"Global Drug Metabolism and Pharmacokinetics Eisai Co., Ltd  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagadeesh","family":"Aluri","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Science Eisai Inc.  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jincao","family":"Wu","sequence":"additional","affiliation":[{"name":"Biostatistics Eisai Inc.  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley S.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Early Phase Research MAC Clinical Research  UK"},{"name":"Fortrea Clinical Research Unit Ltd., UK (at the time of the study)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Laing","sequence":"additional","affiliation":[{"name":"Fortrea Clinical Research Unit Ltd.  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Dutta","sequence":"additional","affiliation":[{"name":"Oncology Clinical Research Eisai Inc.  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanae","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Deep Human Biology Learning Eisai Co., Ltd  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.012"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.016"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-0782"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-25-0725"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.TPS3169"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2022-CT523"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.4_suppl.106"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12466"},{"key":"e_1_2_11_10_1","volume-title":"Guidance recap podcast: clinical pharmacology considerations for human radiolabeled mass balance studies","author":"US Food and Drug Administration"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.119.088344"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2012.04391.x"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3121"},{"key":"e_1_2_11_14_1","volume-title":"Guideline on the investigation of drug interactions","author":"European Medicines Agency"},{"key":"e_1_2_11_15_1","volume-title":"Clinical pharmacology considerations for human radiolabeled mass balance studies: guidance for industry","author":"US Food and Drug Administration"},{"key":"e_1_2_11_16_1","volume-title":"Biopharmaceutic studies","author":"Therapeutic Goods Administration"},{"key":"e_1_2_11_17_1","volume-title":"ICH guideline M3(R2) on non\u2010clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals","author":"European Medicines Agency"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1369079"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12540"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.03.012"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13403"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.16_suppl.5599"},{"key":"e_1_2_11_23_1","volume-title":"Accelerator Mass Spectrometry (AMS) Systems","author":"National Electrostatics Corporation"},{"key":"e_1_2_11_24_1","volume-title":"Ultra\u2010sensitive AMS","author":"Pharmaron"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602530600952172"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2020.08.006"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2092"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2020.09.058"},{"issue":"4","key":"e_1_2_11_29_1","first-page":"413","article-title":"Palonosetron (Aloxi): a second\u2010generation 5\u2010HT3 receptor antagonist for chemotherapy\u2010induced nausea and vomiting","volume":"19","author":"De Leon A","year":"2006","journal-title":"Proc (Bayl Univ Med Cent)"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.06-5251.2001.00028.x"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12549"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1021"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1386"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.1777"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.066282"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-018-0483-9"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1584"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018943613122"},{"key":"e_1_2_11_39_1","unstructured":"PathakSM HayataN O'HaraK et\u00a0al.Open label single center 2 part parallel study to determine the absolute bioavailability and the absorption metabolism and elimination properties of [14C]E7386 in healthy male subjects. Paper presented at:AAPS PharmSci 360; October 20\u201323 2024;Salt Lake City UT USA."}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70202","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70202","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:35:40Z","timestamp":1784547340000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/jcph.70202"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70202","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70202"}}