{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:11:02Z","timestamp":1788379862865,"version":"build-2803163510"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Edoxaban 60\u00a0mg is approved for stroke prevention in patients with atrial fibrillation (AF) not fulfilling any dose\u2010reduction criteria. As edoxaban is partially renally cleared (\u224850%), this study compared pharmacokinetics (PK) and pharmacodynamics of edoxaban 60\u00a0mg once daily with edoxaban 75\u00a0mg once daily in patients with AF with high renal clearance (creatinine clearance &gt;\u00a0100\u00a0mL\/min) over 12 months. Primary PK and pharmacodynamics end points were plasma edoxaban exposure and anti\u2013factor Xa (FXa) concentration. A population PK model estimated edoxaban exposure at steady state. Efficacy and safety outcomes included composites of stroke, transient ischemic attack, systemic embolism, and major and clinically relevant nonmajor bleeding. Of 607 patients, 303 and 304 were randomized to edoxaban 60 and 75\u00a0mg, respectively. Edoxaban 75\u00a0mg provided \u224825% higher exposure than 60\u00a0mg. This increase was accurately depicted in the population PK model; anti\u2013factor Xa concentration correlated with edoxaban exposure. Rates of composite and individual outcomes were similarly low between doses. In conclusion, the 25% increase in edoxaban dose (60\u201075\u00a0mg) resulted in \u224825% exposure increase in the 75\u2010mg group. Higher exposure was not associated with reduced stroke risk in patients with AF with high renal clearance.<\/jats:p>","DOI":"10.1002\/cpdd.1050","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T03:56:06Z","timestamp":1638935766000},"page":"666-674","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Edoxaban Exposure in Patients With Atrial Fibrillation and Estimated Creatinine Clearance Exceeding 100\u00a0mL\/min"],"prefix":"10.1002","volume":"11","author":[{"given":"Ophelia","family":"Yin","sequence":"first","affiliation":[{"name":"Daiichi Sankyo Inc.  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