{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T23:48:23Z","timestamp":1751932103995},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T00:00:00Z","timestamp":1460678400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:p>Edoxaban exposure\u2010response relationships from the phase III study evaluating edoxaban for prevention and treatment of venous thromboembolism (VTE) in patients with acute deep vein thrombosis (DVT) and\/or pulmonary embolism (PE) were assessed by parametric time\u2010to\u2010event analysis. Statistical significant exposure\u2010response relationships were recurrent VTE with hazard ratio (HR) based on average edoxaban concentration at steady state (C<jats:sub>av<\/jats:sub>) (HR<jats:sub>Cav<\/jats:sub>)\u2009=\u20090.98 (i.e., change in the HR with every 1 ng\/mL increase of C<jats:sub>av<\/jats:sub>); the composite of recurrent DVT and nonfatal PE with HR<jats:sub>Cav<\/jats:sub>\u2009=\u20090.99; and the composite of recurrent DVT, nonfatal PE, and all\u2010cause mortality HR<jats:sub>Cav<\/jats:sub>\u2009=\u20090.98, and all death using maximal edoxaban concentration (C<jats:sub>max<\/jats:sub>) with HR (C<jats:sub>max<\/jats:sub>)\u2009=\u20090.99. No statistical significant exposure\u2010response relationships were found for clinically relevant bleeding or major adverse cardiovascular event. Results support the recommendation of once\u2010daily edoxaban 60 mg, and a reduced 30 mg dose in patients with moderate renal impairment, body weight \u226460 kg, or use of P\u2010glycoprotein inhibitors verapamil or quinidine.<\/jats:p>","DOI":"10.1002\/psp4.12077","type":"journal-article","created":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T12:42:47Z","timestamp":1460724167000},"page":"222-232","source":"Crossref","is-referenced-by-count":11,"title":["Edoxaban Exposure\u2010Response Analysis and Clinical Utility Index Assessment in Patients With Symptomatic Deep\u2010Vein Thrombosis or Pulmonary Embolism"],"prefix":"10.1002","volume":"5","author":[{"given":"J","family":"Nyberg","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"KE","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"J\u00f6nsson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"OQP","family":"Yin","sequence":"additional","affiliation":[{"name":"Modeling and Simulation, Translational Medicine, and Clinical Pharmacology Daiichi Sankyo Pharma Development Edison New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Miller","sequence":"additional","affiliation":[{"name":"Modeling and Simulation, Translational Medicine, and Clinical Pharmacology Daiichi Sankyo Pharma Development Edison New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MO","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"USH","family":"Simonsson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,4,15]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.007478"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH09-05-0327"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-0670"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03064.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.53"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.112.046888"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.054866"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40256-013-0029-0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306638"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.541"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12727"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2005.04.005"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2003.11.003"},{"key":"e_1_2_8_14_1","volume-title":"NONMEM Users' Guide","author":"Beal S.L.","year":"1998"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-2607(98)00067-4"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61943-7"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.159.5.457"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2013.07.017"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2011.09.013"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-9560-12-21"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e3182970991"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0108"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH08-03-0193"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpsp4.12077","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.12077","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.12077","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.12077","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T22:59:06Z","timestamp":1696460346000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.12077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1002\/psp4.12077"],"URL":"https:\/\/doi.org\/10.1002\/psp4.12077","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4]]}}}