{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T15:16:23Z","timestamp":1777302983212,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T00:00:00Z","timestamp":1749945600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The pharmacokinetic (PK) profile of remimazolam, a ultra\u2010short\u2010acting benzodiazepine, has been investigated for procedural sedation and anesthesia, but its pharmacokinetics, pharmacodynamics, and optimal dosing for ICU sedation are still unclear. This prospective, single\u2010center, double\u2010blind randomized controlled trial studied ICU adults on mechanical ventilation for over 24\u2009h. Participants were divided into three groups, each receiving a 0.2\u2009mg\/kg remimazolam loading dose in less than a minute, followed by maintenance doses of 0.1, 0.3, or 0.5\u2009mg\/kg\/h. Plasma concentrations of remimazolam and its metabolites were measured using UPLC\u2010MS\/MS, and pharmacokinetic parameters were calculated using one\u2010compartmental methods with WinNolin. The study also assessed pharmacodynamic indicators (RASS score) and the impact of the clinical indicators on pharmacokinetic parameters. The study on 36 ICU patents using a one\u2010compartment model found that after 24\u2009h of continuous intravenous remimazolam infusion, the drug had a median clearance rate of 22.23\u2009mL\/kg\/min and a volume of distribution of 2656.58\u2009mL\/kg. The half\u2010life was 101.791\u2009min in ventilated patients, while its metabolites had a slower clearance rate of 0.49\u2009mL\/kg\/min and an longer half\u2010life of 656.02\u2009min. Sedation levels were mild to moderate at dosed of 0.1\u20130.3\u2009mg\/kg\/h. Liver function significantly affected remimazolam metabolism, influencing the half\u2010life (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.36, <jats:italic>p<\/jats:italic>\u2009=\u20090.00013) and clearance (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.13, <jats:italic>p<\/jats:italic>\u2009=\u20090.04). The pharmacokinetic study indicates that remimazolam is effective and safe for ICU patients on mechanical ventilation, with a 24\u2010h infusion demonstrating rapid clarence and a clear dose\u2010effect relationship. It provides mild to moderate sedation at 0.1\u20130.3\u2009mg\/kg\/h, but caution is advised for patients with severe liver dysfunction due to its impact on drug metabolism.<\/jats:p><jats:p><jats:bold>Trial Registration:<\/jats:bold> <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> identifier: NCT05480787<\/jats:p>","DOI":"10.1002\/prp2.70130","type":"journal-article","created":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T12:15:52Z","timestamp":1749989752000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in <scp>ICU<\/scp> Patients With Mechanical Ventilation: A Preliminary Study"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-5547","authenticated-orcid":false,"given":"Jing","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Litao","family":"Shao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Pharmaceutical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengxiang","family":"Su","sequence":"additional","affiliation":[{"name":"China National Narcotics Control Commission\u2010China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5542-6362","authenticated-orcid":false,"given":"Xiangrong","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu People's Republic of 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