{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T15:14:55Z","timestamp":1769354095112,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"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":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Valemetostat tosylate (valemetostat) is a dual inhibitor of enhancer of zeste homolog (EZH) 2 and EZH1, approved in Japan for the treatment of relapsed\/refractory peripheral T\u2010cell lymphoma and adult T\u2010cell leukemia\/lymphoma. This Phase I, open\u2010label study evaluated the pharmacokinetics and safety of a single 50\u2010mg oral dose of valemetostat in participants with hepatic impairment (HI). In total, 24 participants were enrolled into 3 cohorts of mild HI (n\u00a0=\u00a08) and moderate HI (n\u00a0=\u00a08) according to the National Cancer Institute's Organ Dysfunction Working Group criteria, and matched healthy participants with normal hepatic function (HF; n\u00a0=\u00a08). In participants with mild and moderate HI, total valemetostat (bound\u00a0+\u00a0unbound) area under the concentration\u2010time curve extrapolated to infinity was 23% lower (geometric mean ratio [GMR], 77.2% [90% confidence interval (CI), 44.0\u2010135]) and 35% lower, (GMR, 64.8% [90% CI, 40.6\u2010103]), respectively, and unbound valemetostat was 19% lower (GMR, 81.1% [90% CI, 47.4\u2010139]) and 15% higher (GMR, 115% [90% CI, 75.5\u2010176]), than in participants with normal HF. No treatment\u2010related adverse events were reported. Based on the result of this trial, no dosing adjustments are recommended for patients with mild to moderate HI receiving valemetostat.<\/jats:p>","DOI":"10.1002\/cpdd.1544","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T09:33:33Z","timestamp":1747215213000},"page":"631-641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of Mild to Moderate Hepatic Impairment on Valemetostat Pharmacokinetics: An Open\u2010Label, Phase I Study"],"prefix":"10.1002","volume":"14","author":[{"given":"Masaya","family":"Tachibana","sequence":"first","affiliation":[{"name":"Quantitative Clinical Pharmacology Department Daiichi Sankyo Co., Ltd Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thuy Vu","family":"Craveiro","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology Daiichi Sankyo Inc. 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