{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:58:18Z","timestamp":1790621898795,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The aim of this study is to evaluate the effects of multiple doses of esomeprazole, a strong proton pump inhibitor and acid\u2010reducing agent, on the pharmacokinetics and safety of vepdegestrant, a PROteolysis TArgeting Chimera oestrogen receptor degrader.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a Phase 1, open\u2010label, two\u2010period, crossover, single\u2010dose study in healthy adult participants. During Period 1, on Day 1, a single oral dose of vepdegestrant 200\u2009mg was administered with a moderate\u2010fat meal following overnight fasting. During Period 2, esomeprazole 40\u2009mg was administered once daily on Days 1\u20135; a single dose of vepdegestrant 200\u2009mg was given with a moderate\u2010fat meal on Day 5 following esomeprazole 40\u2009mg. Serial blood samples for vepdegestrant pharmacokinetics and safety laboratory analyses were collected predose and up to 168\u2009h after vepdegestrant dosing in each period. Safety was monitored throughout the study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twelve participants were enrolled and treated. Following administration of vepdegestrant with (test) and without (reference) esomeprazole, test\/reference ratios (90% CIs) of the adjusted geometric means for vepdegestrant area under the plasma concentration\u2013time curve from time 0 to infinity and maximum plasma concentration were 83.73% (76.32, 91.86) and 74.11% (63.47, 86.52), respectively. Similar decreases in ARV\u2010473 (vepdegestrant epimer) plasma exposure were observed. All 12 treatment\u2010emergent adverse events experienced by seven participants were mild in severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Coadministration of multiple daily doses of esomeprazole 40\u2009mg with vepdegestrant 200\u2009mg under fed conditions in healthy adult participants resulted in mild decreases in vepdegestrant plasma exposure. Vepdegestrant 200\u2009mg was well tolerated in healthy adult participants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70636","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:35:45Z","timestamp":1781757345000},"page":"3477-3484","source":"Crossref","is-referenced-by-count":1,"title":["Effect of esomeprazole on the pharmacokinetics of vepdegestrant, a PROteolysis TArgeting Chimera oestrogen receptor degrader, in healthy participants"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9696-3164","authenticated-orcid":false,"given":"Lana","family":"Tran","sequence":"first","affiliation":[{"name":"Pfizer, Inc  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naihan","family":"Chen","sequence":"additional","affiliation":[{"name":"Pfizer (China) R&amp;D Co, Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Winton","sequence":"additional","affiliation":[{"name":"Pfizer, Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle T.","family":"Matschke","sequence":"additional","affiliation":[{"name":"Pfizer, Inc.  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita P.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Pfizer, Inc.  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Pfizer, Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Arvinas Operations, Inc.  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8915-1152","authenticated-orcid":false,"given":"Weiwei","family":"Tan","sequence":"additional","affiliation":[{"name":"Pfizer, Inc  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010021\u201000371\u20106"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010023\u201000736\u20103"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201023\u20103465"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2020.07.020"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.1.94"},{"key":"e_1_2_10_7_1","unstructured":"Arvinas.Arvinas announces FDA acceptance of the new drug application for vepdegestrant for the treatment ofESR1m ER+\/HER2\u2212 advanced breast cancer.https:\/\/ir.arvinas.com\/news-releases\/news-release-details\/arvinas-announces-fda-acceptance-new-drug-application. 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