{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:20:16Z","timestamp":1787664016808,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Esomeprazole, a proton pump inhibitor (PPI), is widely approved for gastroesophageal reflux disease (GERD) in adults and pediatrics globally, but prior to December 2022, its oral tablets (20 and 40 mg) were approved only for adults in China. To address unmet needs in Chinese adolescents aged 12\u201317 years, physiologically based pharmacokinetic (PBPK) modeling was employed to extrapolate data and support label extension, leveraging similarities in GERD pathophysiology and PK\/PD relationships across ages and ethnicities.<\/jats:p>\n                  <jats:p>A PBPK model was developed for esomeprazole to capture the enteric\u2010coated formulation's pharmacokinetics. The model was validated against clinical PK studies in Caucasian, Japanese, and Chinese adults and\/or adolescents, demonstrating good predictions of concentration\u2013time profiles and area under the curve (AUC) for CYP2C19\u2010specific genotypes as well as overall populations across these ethnic groups. All predicted\u2010to\u2010observed ratios for AUC fell within 0.5\u2010 to 2.0\u2010fold, with 14 out of 18 predictions within the 0.67\u2010 to 1.5\u2010fold. This robust validation enabled the model's application to predict PK in Chinese adolescents.<\/jats:p>\n                  <jats:p>PBPK predictions for Chinese adolescents indicated that steady\u2010state AUC for 20\u2010 and 40\u2010mg doses was comparable to that in Japanese adolescents and slightly higher than in Caucasian adolescents. By integrating an established PK\/PD relationship between AUC and the percentage of time with intragastric pH &gt;4, once\u2010daily doses of 20 or 40 mg were justified, achieving adequate acid suppression with a favorable safety profile. This PBPK\u2010informed extrapolation was accepted by China's National Medical Products Administration (NMPA), enabling GERD indication extension to adolescents.<\/jats:p>","DOI":"10.1002\/jcph.70255","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:05:16Z","timestamp":1786547116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PBPK Modeling of Esomeprazole to Support Adolescent Pharmacokinetic Extrapolation and Label Extension in Chinese Patients With Gastroesophageal Reflux Disease (GERD)"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0977-6921","authenticated-orcid":false,"given":"Yuwen","family":"Jin","sequence":"first","affiliation":[{"name":"Clinical Pharmacology R&amp;D China AstraZeneca  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Ding","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology R&amp;D China AstraZeneca  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Hua","sequence":"additional","affiliation":[{"name":"Respiratory &amp; Immunology R&amp;D China AstraZeneca  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Duan","sequence":"additional","affiliation":[{"name":"Biometrics and Data Science R&amp;D China AstraZeneca  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Safety R&amp;D China AstraZeneca  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Respiratory &amp; Immunology R&amp;D China AstraZeneca  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8716-707X","authenticated-orcid":false,"given":"Ramesh V","family":"Pandherpur","sequence":"additional","affiliation":[{"name":"Clinical Development BioPharmaceuticals R&amp;D AstraZeneca  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3317-0386","authenticated-orcid":false,"given":"Jin","family":"Dong","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Quantitative Pharmacology Clinical Pharmacology and Safety Sciences R&amp;D, AstraZeneca  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3415-8917","authenticated-orcid":false,"given":"Sharma","family":"Pradeep","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Quantitative Pharmacology Clinical Pharmacology and Safety Sciences R&amp;D, AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0246-3132","authenticated-orcid":false,"given":"Peiming","family":"Ma","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology R&amp;D China AstraZeneca  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8261-8116","authenticated-orcid":false,"given":"Weifeng","family":"Tang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Quantitative Pharmacology Clinical Pharmacology and Safety Sciences R&amp;D, AstraZeneca  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2673-1069","authenticated-orcid":false,"given":"Diansong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Quantitative Pharmacology Clinical Pharmacology and Safety Sciences R&amp;D, AstraZeneca  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.35.040195.001425"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/59.14.1333"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn311367\u201020200918\u201000558"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.19538\/j.ek2019120602"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.5414\/cp203488"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.1899"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12101"},{"key":"e_1_2_10_9_1","unstructured":"Technical Guideline on Extrapolation of Adult Drug Data to Pediatric Population.2017. 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