{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T02:08:52Z","timestamp":1773367732744,"version":"3.50.1"},"reference-count":12,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Encorafenib is a novel kinase inhibitor of <jats:italic>BRAF<\/jats:italic> V600E as well as wild\u2010type BRAF and CRAF and has received approval, in combination with binimetinib, to treat <jats:italic>BRAF<\/jats:italic> V600E or V600K mutation\u2010positive unresectable or metastatic melanoma or in combination with cetuximab to treat <jats:italic>BRAF<\/jats:italic> V600E mutation\u2010positive colorectal cancer. The absorption, distribution, metabolism and excretion (ADME) of encorafenib was studied by administering [<jats:sup>14<\/jats:sup>C] encorafenib (100\u2009mg containing 90\u2009\u03bcCi of radiolabeled material) to 4 healthy male subjects (NCT01436656). Following a single oral 100\u2010mg dose of [<jats:sup>14<\/jats:sup>C] encorafenib to healthy male subjects, the overall recovery of radioactivity in the excreta was \u226593.9% in all four subjects, indicating that good mass balance was achieved. An equal mean of 47.2% for the radioactivity dose was eliminated in the feces and urine. The percentage of the dose eliminated in the feces (5.0%) and urine (1.8%) as unchanged encorafenib was minor. Metabolism was found to be the major clearance pathway (~88% of the recovered radioactive dose) for encorafenib in humans and is predominantly mediated through N\u2010dealkylation of the isopropyl carbamic acid methyl ester to form the primary phase 1 direct metabolite M42.5 (LHY746). Oral absorption was estimated from the radioactive dose recovered in the urine (47.2%) and the total radioactive dose recovered in the feces as metabolites (39%). Based on these values and the assumptions that encorafenib and its metabolites are stable in feces, the fraction of oral absorption was estimated to be at least ~86%.<\/jats:p>","DOI":"10.1002\/prp2.1140","type":"journal-article","created":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T04:20:51Z","timestamp":1696047651000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A phase I, single\u2010center, open\u2010label study to investigate the absorption, distribution, metabolism and excretion of encorafenib following a single oral dose of 100\u2009mg [<scp><sup>14<\/sup>C<\/scp>] encorafenib in healthy male subjects"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4791-8655","authenticated-orcid":false,"given":"Lance","family":"Wollenberg","sequence":"first","affiliation":[{"name":"Pfizer Inc. Worldwide Research Development and Medical  Boulder Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Hahn","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Worldwide Research Development and Medical  Boulder Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Williams","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Worldwide Research Development and Medical  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Litwiler","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Worldwide Research Development and Medical  Boulder Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00766"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1002011"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2785"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2018.10.003"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx401"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60868-X"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908075"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2923"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3550"},{"key":"e_1_2_10_11_1","volume-title":"BRAFTOVI\u00ae (Encorafenib, [Package Insert])","author":"Lemery SJ","year":"2020"},{"key":"e_1_2_10_12_1","unstructured":"Pfizer.Pharmacokinetic Drug\u2010drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600\u2010mutant Melanoma or Other Advanced Solid Tumors. ClinicalTrials.gov identifier: NCT03864042. Updated November 25 2022. Accessed December 05 2022.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03864042"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602532.2016.1181081"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.1140","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T07:42:15Z","timestamp":1697528535000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.1140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,29]]},"references-count":12,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1002\/prp2.1140"],"URL":"https:\/\/doi.org\/10.1002\/prp2.1140","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,29]]},"assertion":[{"value":"2023-08-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01140"}}