{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:26:23Z","timestamp":1788459983025,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T00:00:00Z","timestamp":1661558400000},"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":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acalabrutinib is a Bruton tyrosine kinase (BTK) inhibitor approved to treat adults with chronic lymphocytic leukemia, small lymphocytic lymphoma, or previously treated mantle cell lymphoma. As the bioavailability of the acalabrutinib capsule (AC) depends on gastric pH for solubility and is impaired by acid\u2010suppressing therapies, coadministration with proton\u2010pump inhibitors (PPIs) is not recommended. Three studies in healthy subjects (N\u00a0=\u00a030, N\u00a0=\u00a066, N\u00a0=\u00a020) evaluated the pharmacokinetics (PKs), pharmacodynamics (PDs), safety, and tolerability of acalabrutinib maleate tablet (AT) formulated with pH\u2010independent release. Subjects were administered AT or AC (orally, fasted state), AT in a fed state, or AT in the presence of a PPI, and AT or AC via nasogastric (NG) route. Acalabrutinib exposures (geometric mean [% coefficient of variation, CV]) were comparable for AT versus AC (AUC<jats:sub>inf<\/jats:sub> 567.8\u00a0ng\u00a0h\/mL [36.9] vs 572.2\u00a0ng\u00a0h\/mL [38.2], C<jats:sub>max<\/jats:sub> 537.2\u00a0ng\/mL [42.6] vs 535.7\u00a0ng\/mL [58.4], respectively); similar results were observed for acalabrutinib's active metabolite (ACP\u20105862) and for AT\u2010NG versus AC\u2010NG. The geometric mean C<jats:sub>max<\/jats:sub> for acalabrutinib was lower when AT was administered in the fed versus the fasted state (C<jats:sub>max<\/jats:sub> 255.6\u00a0ng\/mL [%CV, 46.5] vs 504.9\u00a0ng\/mL [49.9]); AUCs were similar. For AT\u00a0+\u00a0PPI, geometric mean C<jats:sub>max<\/jats:sub> was lower (371.9\u00a0ng\/mL [%CV, 81.4] vs 504.9\u00a0ng\/mL [49.9]) and AUC<jats:sub>inf<\/jats:sub> was higher (AUC<jats:sub>inf<\/jats:sub> 694.1\u00a0ng\u00a0h\/mL [39.7] vs 559.5\u00a0ng\u00a0h\/mL [34.6]) than AT alone. AT and AC were similar in BTK occupancy. Most adverse events were mild with no new safety concerns. Acalabrutinib formulations were comparable and AT could be coadministered with PPIs, food, or via NG tube without affecting the PKs or PDs.<\/jats:p>","DOI":"10.1002\/cpdd.1153","type":"journal-article","created":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T10:06:51Z","timestamp":1661594811000},"page":"1294-1307","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton\u2010Pump Inhibitors"],"prefix":"10.1002","volume":"11","author":[{"given":"Shringi","family":"Sharma","sequence":"first","affiliation":[{"name":"AstraZeneca  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Pepin","sequence":"additional","affiliation":[{"name":"New Modalities and Parenteral Development Pharmaceutical Technology &amp; Development Operations AstraZeneca  Macclesfield, England UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harini","family":"Burri","sequence":"additional","affiliation":[{"name":"AstraZeneca  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianqing","family":"Zheng","sequence":"additional","affiliation":[{"name":"AstraZeneca  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Kuptsova\u2010Clarkson","sequence":"additional","affiliation":[{"name":"AstraZeneca  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"de Jong","sequence":"additional","affiliation":[{"name":"Acerta Pharma B.V.  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