{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:35:40Z","timestamp":1791898540451,"version":"4.3.4"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Treatment of acid\u2010related disorders relies on gastric acid suppression. The percentage of time intragastric pH is &gt;4 (pH\u2009&gt;4 holding time ratio [HTR]) is important for healing erosive oesophagitis; and the pH\u2009&gt;6 HTR is critical for eradication of <jats:italic>Helicobacter pylori<\/jats:italic> infection, as bacterial replication is active and antibiotic effectiveness is optimised. Vonoprazan, a potassium\u2010competitive acid blocker approved in the USA and other countries, suppresses gastric acid secretion in a predictable, rapid and consistent manner, extended over prolonged periods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To explore the relationship between vonoprazan exposure and pH HTR through a pharmacokinetic\/pharmacodynamic (PK\/PD) model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We pooled data from Phase 1 studies with intragastric pH measurements. Pharmacokinetic profiles were predicted for study participants using an existing population pharmacokinetic model. Pharmacokinetic and pharmacodynamic data were merged, and three direct\u2010link PK\/PD models were derived and used to simulate pH HTRs with between\u2010participant variability for pH\u2009&gt;4, &gt;5 and\u2009&gt;6, for vonoprazan doses of 20\u2009mg once and twice daily.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We used data from five Phase 1 studies to derive the PK\/PD model. These included 245 participants (95.1% male, 50.6% Japanese and 49.4% non\u2010Asian). Pre\u2010dose, the mean pH\u2009&gt;4 HTR was 6.4%, pH\u2009&gt;5 3.2% and pH\u2009&gt;6 1.2%. After 7\u2009days of dosing, simulations predicted pH\u2009&gt;4 HTRs of 89.7% and 98.1%, and pH\u2009&gt;6 HTRs of 53.1% and 75.3%, for vonoprazan 20\u2009mg once and twice daily, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Vonoprazan 20\u2009mg once\u2010 and twice\u2010daily dosing demonstrated high, dose\u2010dependent, 24\u2010hour intragastric acid control in this PK\/PD model, supporting clinical efficacy data in patients with acid\u2010related disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17510","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T08:19:31Z","timestamp":1681719571000},"page":"16-25","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A translational pharmacokinetic\/pharmacodynamic approach supports optimal vonoprazan dosing for erosive oesophagitis and <i>Helicobacter pylori<\/i> infection"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5645-857X","authenticated-orcid":false,"given":"Carmelo","family":"Scarpignato","sequence":"first","affiliation":[{"name":"Department of Health Sciences United Campus of Malta  Msida Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0987-0662","authenticated-orcid":false,"given":"Colin W.","family":"Howden","sequence":"additional","affiliation":[{"name":"University of Tennessee College of Medicine  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eckhard","family":"Leifke","sequence":"additional","affiliation":[{"name":"Phathom Pharmaceuticals, Research and Development  Buffalo Grove Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darcy J.","family":"Mulford","sequence":"additional","affiliation":[{"name":"Phathom Pharmaceuticals, Research and Development  Buffalo Grove Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gezim","family":"Lahu","sequence":"additional","affiliation":[{"name":"thinkQ<sup>2<\/sup> AG  Oberneuhofstrasse 5 Baar Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Facius","sequence":"additional","affiliation":[{"name":"thinkQ<sup>2<\/sup> AG  Oberneuhofstrasse 5 Baar Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4667-330X","authenticated-orcid":false,"given":"Richard","family":"Hunt","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology McMaster University  Hamilton Ontario Canada"},{"name":"Farncombe Family Digestive Health Research Institute McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16295"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001735"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13121"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13325"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1009"},{"key":"e_1_2_10_7_1","unstructured":"PhathomPI.VOQUEZNA prescribing information.2022."},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ctg.2015.18"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0718-z"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2006.03235.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000200917"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.159.7.649"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/39.1.5"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12059"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.43.2008.S56"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.11.059"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2019"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-5193(68)90188-4"},{"key":"e_1_2_10_19_1","unstructured":"BealSL SheinerLB.NONMEM users guide. 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