{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:04:15Z","timestamp":1785150255395,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002462","name":"Chungnam National University","doi-asserted-by":"publisher","award":["RS\u20102022\u201000155857"],"award-info":[{"award-number":["RS\u20102022\u201000155857"]}],"id":[{"id":"10.13039\/501100002462","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102023\u201000278597"],"award-info":[{"award-number":["RS\u20102023\u201000278597"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102022\u2010NR069643"],"award-info":[{"award-number":["RS\u20102022\u2010NR069643"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102022\u2010NR070856"],"award-info":[{"award-number":["RS\u20102022\u2010NR070856"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003052","name":"Ministry of Trade, Industry and Energy","doi-asserted-by":"publisher","award":["RS\u20102024\u201000434342"],"award-info":[{"award-number":["RS\u20102024\u201000434342"]}],"id":[{"id":"10.13039\/501100003052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009950","name":"Ministry of Education","doi-asserted-by":"publisher","award":["RS\u20102025\u201025397599"],"award-info":[{"award-number":["RS\u20102025\u201025397599"]}],"id":[{"id":"10.13039\/100009950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Potassium\u2010competitive acid blockers (PCABs) are emerging alternatives to proton pump inhibitors for the treatment of acid\u2010related diseases. However, due to the complex, nonlinear interaction between drug exposure, food intake, and physiological rhythms, optimizing dosing strategies remains challenging. A multi\u2010leveled population analysis was conducted using published pharmacokinetic and pharmacodynamic data on four representative PCABs: tegoprazan, YH4808, fexuprazan, and vonoprazan. A semi\u2010mechanistic population PK\/PD model was developed to account for food effects, circadian pH rhythms, and pH\u2010dependent drug absorption. A multi\u2010level nonlinear mixed\u2010effects modeling framework was implemented to capture both inter\u2010drug and inter\u2010study variability. The model successfully described the time course of plasma concentration and intragastric pH for all four PCABs under various conditions. The model identified differences in pharmacokinetics and pharmacodynamic potency between drugs (with the relative in\u00a0vitro potency ranked as vonoprazan\u2009&gt;\u2009fexuprazan\u2009&gt;\u2009YH4808\u2009&gt;\u2009tegoprazan), and simulations demonstrated that both pre\u2010 and post\u2010meal administration enhanced pH control in early time period via potentially distinct mechanisms: the pre\u2010meal effect may arise from temporally separated contributions of food\u2010 and drug\u2010induced pH elevation, whereas the post\u2010meal effect is likely driven by temporally overlapping, additive actions, particularly under low\u2010dose or non\u2010steady\u2010state conditions. Predicted pH profiles and holding times above pH\u20094 closely matched reported clinical outcomes. The study demonstrates the application of a mechanistic, multi\u2010level population approach for cross\u2010drug PK\/PD evaluation of PCABs. The findings support drug\u2010specific dose optimization and highlight the clinical relevance of food\u2013drug interactions. The modeling approach provides a model platform for pharmacotherapy or model\u2010informed drug development (MIDD).<\/jats:p>","DOI":"10.1002\/psp4.70181","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T06:37:38Z","timestamp":1768545458000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Mechanism\u2010Based Multi\u2010Level Population PK\/PD Model for Potassium\u2010Competitive Acid Blockers"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-597X","authenticated-orcid":false,"given":"Woojin","family":"Jung","sequence":"first","affiliation":[{"name":"College of Pharmacy and Institute of Drug Research and Development Chungnam National University  Daejeon Republic of Korea"},{"name":"Senior Health Convergence Research Center Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4420-0533","authenticated-orcid":false,"given":"Jaeyeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Team, Clinical Science Group, Clinical Development and Medical Division Yuhan Corporation  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4175-4189","authenticated-orcid":false,"given":"Hyeseon","family":"Jeon","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Drug Research and Development Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taewook","family":"Sung","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Drug Research and Development Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8793-2449","authenticated-orcid":false,"given":"Hwi\u2010yeol","family":"Yun","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Drug Research and Development Chungnam National University  Daejeon Republic of Korea"},{"name":"Senior Health Convergence Research Center Chungnam National University  Daejeon Republic of Korea"},{"name":"Department of Bio\u2010AI Convergence Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5799-4489","authenticated-orcid":false,"given":"Soyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Drug Research and Development Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6026-7063","authenticated-orcid":false,"given":"Jung\u2010woo","family":"Chae","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Drug Research and Development Chungnam National University  Daejeon Republic of Korea"},{"name":"Senior Health Convergence Research Center Chungnam National University  Daejeon Republic of Korea"},{"name":"Department of Bio\u2010AI Convergence Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12262\u2010021\u201003189\u2010z"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16017"},{"issue":"12","key":"e_1_2_9_4_1","first-page":"693","article-title":"Potassium\u2010Competitive Acid Blockers: Present and Potential Utility in the Armamentarium for Acid Peptic Disorders","volume":"18","author":"Wong N.","year":"2022","journal-title":"Gastroenterology and Hepatology"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm18029"},{"issue":"2","key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1152\/physrev.00016.2019","article-title":"The Physiology of the Gastric Parietal Cell","volume":"100","author":"Engevik A. C.","year":"2019","journal-title":"Physiological Reviews"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12839"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14061298"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15060709"},{"key":"e_1_2_9_10_1","doi-asserted-by":"crossref","unstructured":"T.Hastie R.Tibshirani andJ.Friedman \u201cThe Elements of Statistical Learning \u201d2009 https:\/\/doi.org\/10.1007\/978\u20100\u2010387\u201084858\u20107.","DOI":"10.1007\/978-0-387-84858-7"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14818"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ctg.2015.18"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13121"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15438"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2021.06.007"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.12793\/tcp.2019.27.2.80"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1805"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-020-00986-4"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13091489"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2021.01.026"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16121"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15268"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-022-03201-5"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13060813"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.08.001"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.118.254904"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12958"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.12793\/tcp.2023.31.e11"},{"issue":"1","key":"e_1_2_9_29_1","doi-asserted-by":"crossref","DOI":"10.5009\/gnl220050","article-title":"Comparison of Pharmacodynamics Between Tegoprazan and Dexlansoprazole Regarding Nocturnal Acid Breakthrough: A Randomized Crossover Study","volume":"17","author":"Han S.","year":"2022","journal-title":"Gut and Liver"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15784"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894\u2010024\u201000939\u20103"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14148"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16131"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X17705329"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph18073527"},{"issue":"7","key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1046\/j.1365-2036.2003.01533.x","article-title":"Meal\u2010Stimulated Gastric Acid Secretion and Integrated Gastric Acidity in Gastro\u2010Oesophageal Reflux Disease","volume":"17","author":"Sloan S.","year":"2003","journal-title":"Alimentary Pharmacology & Therapeutics"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9FO03033F"},{"issue":"5","key":"e_1_2_9_38_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.34297\/AJBSR.2021.13.001908","article-title":"Between Biological Relevancy and Statistical Significance\u2014Step for Assessment Harmonization","volume":"13","author":"Costa Duriguetto G.","year":"2021","journal-title":"American Journal of Biomedical Science & Research"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70181","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.70181","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T09:48:49Z","timestamp":1768556929000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/psp4.70181"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70181","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-07-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70181"}}