{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T15:13:21Z","timestamp":1772464401823,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Keverprazan, a novel potassium\u2010competitive acid blocker, was approved for treating acid\u2010related diseases. This study aimed to analyze the safety, pharmacokinetics (PKs) and pharmacodynamics (PDs) of multiple doses of keverprazan. This was a randomized, positive\u2010\/placebo\u2010controlled, phase Ic trial. Twenty\u2010six healthy adults were randomized to receive 20\u2009mg\/day keverprazan (<jats:italic>n<\/jats:italic>\u2009=\u20098), 40\u2009mg\/day keverprazan (<jats:italic>n<\/jats:italic>\u2009=\u20098), placebo (<jats:italic>n<\/jats:italic>\u2009=\u20096), or 20\u2009mg\/day vonoprazan (<jats:italic>n<\/jats:italic>\u2009=\u20094) for 7\u2009days. Safety, PK and PD assessments were conducted. In the keverprazan, vonoprazan, and placebo groups, adverse events (AEs) were reported in nine (56.25%), two (50.00%), and three (50.00%) subjects, respectively. AEs were mild except a moderate abdominal pain leading to withdraw. No serious AEs occurred. The plasma concentration\u2010time profiles of keverprazan showed rapid absorption (median time to maximum plasma concentration of 1.25\u20133.0\u2009h). The terminal half\u2010life was 6.23 and 7.01\u2009h for keverprazan 20 and 40\u2009mg groups on day 7. The maximum plasma concentration was 43.1 and 93.2\u2009ng\/mL, respectively. There was no apparent accumulation of keverprazan and the major metabolite after 7\u2010day administration. The intragastric pH greater than 5 holding time ratios (HTRs) over 24\u2009h postdose increased from 79.1%, 84.4%, and 84.5% on day 1 to 99.0%, 97.4%, and 100.0% on day 7 in the vonoprazan 20\u2009mg and keverprazan 20 and 40\u2009mg groups, respectively. The intragastric pH greater than 5 HTR of keverprazan reached a plateau at 20\u2009mg. Keverprazan is well\u2010tolerable. A steady\u2010state in exposure was generally reached after 7\u2009days of treatment. A dose of 20\u2009mg\/day keverprazan can elicit a significant, stable, and long\u2010lasting gastric acid inhibition effect.<\/jats:p>","DOI":"10.1111\/cts.13598","type":"journal-article","created":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T04:40:49Z","timestamp":1691037649000},"page":"1911-1922","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Keverprazan, a novel potassium\u2010competitive acid blocker: Multiple oral doses safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy subjects"],"prefix":"10.1111","volume":"16","author":[{"given":"Sufeng","family":"Zhou","sequence":"first","affiliation":[{"name":"Phase I Clinical Trial Unit The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Xie","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Chen","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sijia","family":"Ding","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Su","sequence":"additional","affiliation":[{"name":"Jiangsu Carephar Pharmaceutical Co., Ltd.  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8861-7299","authenticated-orcid":false,"given":"Feng","family":"Shao","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit The First Affiliated Hospital with Nanjing Medical University  Nanjing China"},{"name":"Department of Clinical Pharmacology Pharmacy College, Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pop.2017.07.001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.07.045"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32404-7"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2018.12.009"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-313589"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14428"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm18001"},{"key":"e_1_2_11_9_1","volume-title":"StatPearls [Internet]","author":"Ahmed A","year":"2023"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14473"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15438"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.4292\/wjgpt.v9.i7.63"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm18029"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2021.06.007"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12958"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14818"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13121"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.09.041"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16017"},{"issue":"7","key":"e_1_2_11_20_1","first-page":"502","article-title":"Embryo\u2010fetal developmental toxicity and toxicokinetics of carenoprazan hydrochloride in rabbits","volume":"34","author":"Bin Shu YZ","year":"2020","journal-title":"Chin J Pharmacol Toxicol"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2017.06.020"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-020-00986-4"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.15700"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0326-7"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-021-01822-5"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001735"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1009"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13325"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16000"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm.2013.19.1.25"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13598","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T07:31:32Z","timestamp":1697614292000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,2]]},"references-count":29,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1111\/cts.13598"],"URL":"https:\/\/doi.org\/10.1111\/cts.13598","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,2]]},"assertion":[{"value":"2023-04-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}