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This prospective study aimed to investigate the distribution and elimination kinetics of midazolam (MDZ) and its metabolites, and their association with awakening time. The concentrations of MDZ and its seven metabolites were measured immediately and at 4, 8, 12, and 24\u00a0h after the discontinuation of MDZ infusion, using liquid chromatography-tandem mass spectrometry. The area under the time-plasma concentration curve from 0 to 24\u00a0h after MDZ discontinuation (AUC<jats:sub>last<\/jats:sub>) was calculated based on the trapezoidal rule. Of the 15 enrolled patients, seven awakened after the discontinuation of MDZ infusion. MDZ and three of its metabolites were major compounds and their elimination kinetics followed a first-order elimination profile. In the multivariable analysis, only MDZ was associated with awakening time (AUC<jats:sub>last<\/jats:sub>: R<jats:sup>2<\/jats:sup>\u2009=\u20090.59, <jats:italic>p<\/jats:italic>\u2009=\u20090.03; AUC<jats:sub>inf<\/jats:sub>: R<jats:sup>2<\/jats:sup>\u2009=\u20090.96, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Specifically, a 0.001% increase in MDZ AUC was associated with a 1% increase in awakening time. In the individual regression analysis between MDZ concentration and awakening time, the mean MDZ concentration at awakening time was 16.8\u00a0ng\/mL. The AUC of MDZ is the only significant factor associated with the awakening time.<\/jats:p>","DOI":"10.1038\/s41598-024-54968-z","type":"journal-article","created":{"date-parts":[[2024,2,25]],"date-time":"2024-02-25T20:02:04Z","timestamp":1708891324000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Distribution and elimination kinetics of midazolam and metabolites after post-resuscitation care: a prospective observational study"],"prefix":"10.1038","volume":"14","author":[{"given":"Wonjoon","family":"Jeong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung","family":"Sunwoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeonho","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Soo","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Hong","family":"Min","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Nam","family":"In","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong Joon","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So Young","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jang Hee","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Hye","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyein","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"My Tuyen Thi","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaehan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changshin","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,25]]},"reference":[{"key":"54968_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.15441\/ceem.23.012","volume":"10","author":"CW Callaway","year":"2023","unstructured":"Callaway, C. 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