{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:51:22Z","timestamp":1790455882585,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, is approved for the treatment of mantle cell lymphoma and chronic lymphocytic leukaemia. Many critically ill patients are unable to swallow and need oral medications to be delivered via a nasogastric (NG) tube. Furthermore, critically ill patients are typically administered proton\u2010pump inhibitors (PPIs) to prevent stress ulcers. Concomitant administration with PPIs reduces acalabrutinib exposure and is not currently recommended. To evaluate acalabrutinib in subjects co\u2010administered with PPIs who require NG delivery, a phase 1, open\u2010label, randomized, crossover, single\u2010dose study was conducted in healthy subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study assessed the relative bioavailability of an acalabrutinib suspension\u2014in regular, degassed Coca\u2010Cola\u2014administered via NG tube (Acala\u2010NG) versus the pharmacokinetics (PK) of an acalabrutinib capsule administered orally with water. In addition, the PPI effect was evaluated by comparing the PK following Acala\u2010NG in the presence or absence of rabeprazole.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exposure of acalabrutinib and its active metabolite (ACP\u20105862) were comparable following administration of Acala\u2010NG versus the oral capsule (Geo mean ratio, % ref [90% confidence interval, CI]: acalabrutinib AUC<jats:sub>inf<\/jats:sub>: 103 [93\u2010113]; <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>: 144 [120\u2010173]). In addition, exposure was similar following administration of Acala\u2010NG with and without a PPI (Geo mean ratio, % ref [90% CI]: acalabrutinib AUC<jats:sub>inf<\/jats:sub>: 105 [79\u2010138]; <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>: 95 [66\u2010137]). No safety or tolerability concerns were observed, and all adverse events were mild and resolved without treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Acala\u2010NG with or without a PPI is safe and well\u2010tolerated without impeding bioavailability.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15362","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T08:34:06Z","timestamp":1650875646000},"page":"4573-4584","source":"Crossref","is-referenced-by-count":4,"title":["Bioavailability of acalabrutinib suspension delivered via nasogastric tube in the presence or absence of a proton pump inhibitor in healthy subjects"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3120-225X","authenticated-orcid":false,"given":"Shringi","family":"Sharma","sequence":"first","affiliation":[{"name":"Quantitative Clinical Pharmacology AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Pepin","sequence":"additional","affiliation":[{"name":"New Modalities &amp; Parenteral Development, Pharmaceutical Technology &amp; Development, Operations AstraZeneca  Macclesfield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Cheung","sequence":"additional","affiliation":[{"name":"Hematology, Research and Development AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianqing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Late Hematology Statistics, Oncology Biometrics AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wei","sequence":"additional","affiliation":[{"name":"Acerta Pharma (a member of the AstraZeneca Group)  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Townsley","sequence":"additional","affiliation":[{"name":"Oncology Research and Development AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Han","sequence":"additional","affiliation":[{"name":"Parexel International Early Phase Clinical Unit (Los Angeles)  Glendale CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Majewski","sequence":"additional","affiliation":[{"name":"Oncology Research and Development, Clinical Operations, AstraZeneca  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Ware","sequence":"additional","affiliation":[{"name":"Acerta Pharma (a member of the AstraZeneca Group)  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Mann","sequence":"additional","affiliation":[{"name":"Oral Product Development, Pharmaceutical Technology &amp; Development, Operations AstraZeneca  Macclesfield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerendra","family":"Munugalavadla","sequence":"additional","affiliation":[{"name":"Translational Medicine, Hematology, Research and Early Development AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Product Leadership, Pharmaceutical Technology &amp; Development, Operations AstraZeneca  Macclesfield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priti","family":"Patel","sequence":"additional","affiliation":[{"name":"Clinical Development Hematology, Oncology Research and Development AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Gupta","sequence":"additional","affiliation":[{"name":"Oncology Research and Development AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Tomkinson","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Quantitative Pharmacology (CPQP), Clinical Pharmacology and Safety Sciences, Research and Development AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Calquence (acalabrutinib) [Full Prescribing Information]. U.S. Food and Drug Administration website. In Wilmington DE: AstraZeneca Pharmaceuticals LP 2019."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.22190"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007018212822"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000798"},{"issue":"3","key":"e_1_2_11_6_1","first-page":"363","article-title":"A review of rabeprazole in the treatment of acid\u2010related diseases","volume":"3","author":"Pace F","year":"2007","journal-title":"Ther Clin Risk Manag"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.73"},{"key":"e_1_2_11_8_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CEDR).Guidance for Industry: Evaluation of gastric pH\u2010dependent drug interactions with acid\u2010reducing agents: Study design data analysis and clinical implications. In 2020."},{"key":"e_1_2_11_9_1","unstructured":"Center for Drug Evaluation and Research.Acalabrutinib NDA\/BLA Application (210259Orig1s000): Treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. 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