{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T14:43:23Z","timestamp":1783089803232,"version":"3.54.6"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":35,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"JSPS KAKENHI","award":["JP 22K09116"],"award-info":[{"award-number":["JP 22K09116"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["j intensive care"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The pharmacokinetics of prolonged remimazolam infusion in patients undergoing long-term mechanical ventilation remain unclear. This study aimed to evaluate the pharmacokinetics of remimazolam administered continuously for 24\u00a0h.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This open-label pharmacokinetic analysis enrolled patients requiring mechanical ventilation into two groups: the surgical group, which received remimazolam during and after surgery, and the medical ICU group, which received remimazolam in the intensive care unit (ICU). Remimazolam was administered at a fixed rate of 0.1\u00a0mg\/kg\/h for\u2009\u2265\u200924\u00a0h, and blood samples were collected at regular intervals. Plasma remimazolam concentrations were measured by tandem mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty patients (10 in each group) completed the study. The median duration of remimazolam infusion was 24.0\u00a0h in the surgical group and 102.0\u00a0h in the medical ICU group. The steady-state plasma concentrations in both the surgical and medical ICU groups exhibited modest intrasubject variability (4.46\u201332.73%) and moderate intersubject variability (16.45\u201331.71%), with all values falling within clinically acceptable intermediate ranges. The plasma remimazolam concentration at the end of infusion was 130.7\u00a0ng\/mL (95% confidence interval [CI] 115.2\u2013146.1) in the surgical group and 134.3\u00a0ng\/mL (95% CI 98.7\u2013170.0) in the medical ICU group. Noncompartmental analysis showed that the clearance was 54.3 L\/h (95% CI 47.6\u201361.8) and 55.6 L\/h (95% CI 42.8\u201372.1) (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.856), while the volume of distribution at steady state was 284 L (95% CI 215\u2013376) and 316 L (95% CI 142\u2013707) (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.780), with no statistically significant differences between the groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this preliminary study, both the surgical ICU group (approximately 24\u00a0h) and the medical ICU group (beyond 24\u00a0h) showed no evidence of time-dependent accumulation of plasma remimazolam, indicating a generally stable pharmacokinetic profile under the examined conditions.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>Trial registration<\/jats:italic>\n                      : In compliance with the Japanese Clinical Trials Act, the study was classified as a Specified Clinical Trial owing to the use of unapproved pharmaceuticals, which were reviewed by a certified review board (CRB) and registered in the Japan Registry of Clinical Trials (jRCTs041200076) on December 15, 2020.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40560-025-00840-9","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T02:47:29Z","timestamp":1765421249000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prolonged infusion of remimazolam in surgical and medical intensive care unit patients: a pilot pharmacokinetic study"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1156-3311","authenticated-orcid":false,"given":"Yuji","family":"Suzuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matsuyuki","family":"Doi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Mimuro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Mochizuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyasu","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"840_CR1","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1007\/s00134-003-1905-x","volume":"29","author":"B Vasile","year":"2003","unstructured":"Vasile B, Rasulo F, Candiani A, Latronico N. 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