{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:54:03Z","timestamp":1792554843910,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate the effects of vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) oestrogen receptor degrader, on the pharmacokinetics of dabigatran (a P\u2010glycoprotein [P\u2010gp] substrate) and rosuvastatin (a breast cancer resistance protein [BCRP] substrate).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In two phase 1, open\u2010label, two\u2010period, fixed\u2010sequence studies, healthy adult participants received a single oral dose of dabigatran etexilate 75\u2009mg or rosuvastatin 10\u00a0mg alone and with a single dose of vepdegestrant 200\u2009mg. Serial plasma samples were collected after dosing, and pharmacokinetic parameters for dabigatran and rosuvastatin were estimated by standard noncompartmental analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Coadministration of the P\u2010gp substrate dabigatran etexilate with vepdegestrant increased dabigatran area under the concentration\u2013time curve (AUC) from time 0 to infinity by 98% and maximum plasma concentration (\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) by 92%. Coadministration of the BCRP substrate rosuvastatin with vepdegestrant increased rosuvastatin plasma AUC from time 0 to time of the last measurable concentration by 11% and\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      by 21%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Coadministration with vepdegestrant doubled dabigatran exposure and resulted in a minor increase (11%) in rosuvastatin exposure in humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70198","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T02:00:08Z","timestamp":1755568808000},"page":"3501-3510","source":"Crossref","is-referenced-by-count":10,"title":["Effect of vepdegestrant, a PROTAC oestrogen receptor degrader, on dabigatran and rosuvastatin pharmacokinetics in healthy participants"],"prefix":"10.1002","volume":"91","author":[{"given":"Derek Z.","family":"Yang","sequence":"first","affiliation":[{"name":"Pfizer, Inc.  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhou","sequence":"additional","affiliation":[{"name":"Pfizer, Inc.  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Winton","sequence":"additional","affiliation":[{"name":"Pfizer, Inc.  Groton CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle T.","family":"Matschke","sequence":"additional","affiliation":[{"name":"Pfizer, Inc.  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantino","family":"Kantaridis","sequence":"additional","affiliation":[{"name":"Pfizer, Inc.  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Doyle","sequence":"additional","affiliation":[{"name":"Pfizer, Inc.  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Pfizer, Inc.  Groton CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naihan","family":"Chen","sequence":"additional","affiliation":[{"name":"Pfizer, Inc.  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Arvinas Operations, Inc.  New Haven CT 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 CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2020.07.020"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010021\u201000371\u20106"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010023\u201000736\u20103"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201023\u20103465"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.09.567"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538\u20107445.SABCS23\u2010PO3\u201005\u201008"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2024.103240"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2505725"},{"issue":"4","key":"e_1_2_11_10_1","article-title":"VERITAC\u20102: a global, randomized phase 3 study of ARV\u2010471, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, vs fulvestrant in ER+\/human epidermal growth factor receptor 2 (HER2)\u2010advanced breast cancer","volume":"8","author":"Hamilton EP","year":"2023","journal-title":"Ann Oncol"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.16_suppl.TPS1121"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2024.103285"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","unstructured":"VoreM.ABCB subfamily. International Union of Basic and Clinical Pharmacology\/British Pharmacological Society Guide to Pharmacology CITE 2023. Accessed April 14 2025.https:\/\/www.guidetopharmacology.org\/GRAC\/FamilyDisplayForward?familyId=152","DOI":"10.2218\/gtopdb\/F152\/2023.1"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","unstructured":"KerrI.ABCG subfamily. International Union of Basic and Clinical Pharmacology\/British Pharmacological Society Guide to Pharmacology CITE.2023. Accessed April 14 2025.https:\/\/www.guidetopharmacology.org\/GRAC\/FamilyDisplayForward?familyId=155","DOI":"10.2218\/gtopdb\/F155\/2025.3"},{"key":"e_1_2_11_15_1","unstructured":"Pfizer Inc.An interventional phase 1 open\u2010label fixed\u2010sequence 2\u2010period study to evaluate the effect of a single oral dose of ARV\u2010471 (PF\u201007850327) on the pharmacokinetics of dabigatran in healthy participants. Updated November 4 2022. Accessed April 7 2025.https:\/\/cdn.clinicaltrials.gov\/large-docs\/89\/NCT05673889\/Prot_000.pdf"},{"key":"e_1_2_11_16_1","unstructured":"Pfizer Inc.An interventional phase 1 open\u2010label fixed\u2010sequence 2\u2010period study to evaluate the effect of a single oral dose of ARV\u2010471 (PF\u201007850327) on the pharmacokinetics of rosuvastatin in healthy participants. Updated November 4 2022. Accessed April 7 2025.https:\/\/cdn.clinicaltrials.gov\/large-docs\/60\/NCT05652660\/Prot_000.pdf"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/14796694.2024.2377530"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12823"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1213"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538\u20107836.2011.04498.x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16182"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16176"},{"key":"e_1_2_11_24_1","unstructured":"AstraZeneca.CRESTOR (rosuvastatin) tablets for oral use. Prescribing information Updated July2024. Accessed June 10 2024.https:\/\/den8dhaj6zs0e.cloudfront.net\/50fd68b9-106b-4550-b5d0-12b045f8b184\/fd6c9085-0722-46d7-b166-bd68f09c43d5\/fd6c9085-0722-46d7-b166-bd68f09c43d5_viewable_rendition__v.pdf"},{"key":"e_1_2_11_25_1","unstructured":"Boehringer Ingelheim Pharmaceuticals Inc.PRADAXA (dabigatran etexilate) capsules for oral use. Prescribing information. Updated November2023. Accessed June 10 2024.https:\/\/content.boehringer-ingelheim.com\/DAM\/c669f898-0c4e-45a2-ba55-af1e011fdf63\/pradaxa%20capsules-us-pi.pdf"},{"key":"e_1_2_11_26_1","unstructured":"European Medicines Agency.Guideline on the investigation of drug interactions. Updated June 21 2012. Accessed June 25 2024.https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-investigation-drug-interactions-revision-1_en.pdf"},{"key":"e_1_2_11_27_1","unstructured":"Food and Drug Administration US Department of Health and Human Services.M12 clinical drug interaction studies. Updated August2024. Accessed September 4 2024 https:\/\/www.fda.gov\/media\/161199\/download"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.019083"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation\u20102006.1.450"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010020\u201000867\u20101"},{"key":"e_1_2_11_31_1","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH harmonised guideline: drug interaction studies (M12). Updated May 21 2024. Accessed April 7 2025.https:\/\/database.ich.org\/sites\/default\/files\/ICH_M12_Step4_Guideline_2024_0521_0.pdf"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2012.04453.x"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01201\u201017"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318\u2010019\u201000577\u20105"},{"key":"e_1_2_11_35_1","unstructured":"Center for Drug Evaluation and Research.NDA multi\u2010disciplinary review and evaluation. Abrocitinib tablets. Application number: 213871Orig1s000 Updated October 12 2018. Accessed September 18 2024.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2022\/213871Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_11_36_1","volume-title":"Drug absorption","author":"Alagga AA","year":"2025"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28227532"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2005.06.005"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13118"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40268\u2010015\u20100120\u2010x"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0009\u20109236(02)17633\u20108"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318\u2010017\u20100427\u20109"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0149\u20102918(03)80316\u20108"},{"key":"e_1_2_11_44_1","unstructured":"Food and Drug Administration.Drug development and drug interactions: table of substrates inhibitors and inducers. Updated June 5 2023. Accessed September 4 2024.https:\/\/www.fda.gov\/drugs\/drug-interactions-labeling\/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70198","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T09:28:22Z","timestamp":1764149302000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,18]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/bcp.70198"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70198","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,18]]}}}