{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:02:22Z","timestamp":1770897742203,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T00:00:00Z","timestamp":1644883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acalabrutinib received approval for the treatment of adult patients with mantle cell lymphoma who received at least 1 prior therapy and adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. This study investigated the impact of hepatic impairment (HI) on acalabrutinib pharmacokinetics (PK) and safety at a single 50\u2010mg dose in fasted subjects. This study was divided into 2 parts: study 1, an open\u2010label, parallel\u2010group study in Child\u2010Pugh class A or B subjects and healthy subjects; and study 2, an open\u2010label, parallel\u2010group study in Child\u2010Pugh class C subjects and healthy subjects. Baseline characteristics and safety profiles were similar across groups. Acalabrutinib exposure (area under the plasma concentration\u2013time curve) increased slightly (1.90\u2010 and 1.48\u2010fold) in subjects with mild (Child\u2010Pugh class A) and moderate (Child\u2010Pugh class B) hepatic impairment compared with healthy subjects. In severe hepatic impairment (Child\u2010Pugh class C), acalabrutinib exposure (area under the plasma concentration\u2013time curve and maximum plasma concentration) increased \u22485.0\u2010 and 3.6\u2010fold, respectively. Results were consistent across total and unbound exposures. Severe hepatic impairment did not impact total\/unbound metabolite (ACP\u20105862) exposures; the metabolite\u2010to\u2010parent ratio decreased to 0.6 to 0.8 (vs 3.1\u20103.6 in healthy subjects). In summary, single oral dose of 50\u2010mg acalabrutinib was safe and well tolerated in subjects with mild, moderate, and severe hepatic impairment and in healthy control subjects. In subjects with severe hepatic impairment, mean acalabrutinib exposure increased by up to 5\u2010fold and should be avoided. Acalabrutinib does not require dose adjustment in patients with mild or moderate hepatic impairment.<\/jats:p>","DOI":"10.1002\/jcph.2013","type":"journal-article","created":{"date-parts":[[2021,12,12]],"date-time":"2021-12-12T15:09:10Z","timestamp":1639321750000},"page":"812-822","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluation of the Pharmacokinetics and Safety of a Single Dose of Acalabrutinib in Subjects With Hepatic Impairment"],"prefix":"10.1002","volume":"62","author":[{"given":"Yan","family":"Xu","sequence":"first","affiliation":[{"name":"Quantitative Clinical Pharmacology AstraZeneca  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Izumi","sequence":"additional","affiliation":[{"name":"Clinical Development AstraZeneca  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Clinical Development AstraZeneca  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kwan","sequence":"additional","affiliation":[{"name":"Clinical Development AstraZeneca  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard","family":"Kuo","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology AstraZeneca  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeannine","family":"Madere","sequence":"additional","affiliation":[{"name":"Clinical Development AstraZeneca  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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