{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T03:32:55Z","timestamp":1787887975004,"version":"build-2784847793"},"reference-count":33,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015237","name":"Medicines Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015237","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004374","name":"Medtronic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004374","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bjanaesthesia.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["British Journal of Anaesthesia"],"published-print":{"date-parts":[[2023,8]]},"DOI":"10.1016\/j.bja.2023.04.035","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T06:28:52Z","timestamp":1685600932000},"page":"284-293","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"title":["Development of a pharmacokinetic and pharmacodynamic model for intranasal administration of midazolam in older adults: a single-site two-period crossover study"],"prefix":"10.1016","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1216-0576","authenticated-orcid":false,"given":"Clemens","family":"Barends","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izaak","family":"den Daas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mendy","family":"Driesens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Visser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Absalom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3616-5539","authenticated-orcid":false,"given":"Pieter","family":"Colin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bja.2023.04.035_bib1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/00000542-199102000-00007","article-title":"Plasma concentrations of midazolam in children following intranasal administration","volume":"74","author":"Walbergh","year":"1991","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2023.04.035_bib2","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1046\/j.1365-2125.2002.01588.x","article-title":"Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers","volume":"53","author":"Knoester","year":"2002","journal-title":"Br J Clin Pharmacol"},{"key":"10.1016\/j.bja.2023.04.035_bib3","unstructured":"Alzheimer Nederland. Factsheet\u00a0alzheimer 2017. Available from https:\/\/www.alzheimer-nederland.nl\/sites\/default\/files\/directupload\/factsheet-dementie-algemeen.pdf (accessed 7 August 2018)."},{"key":"10.1016\/j.bja.2023.04.035_bib4","series-title":"Dementia","year":"2019"},{"key":"10.1016\/j.bja.2023.04.035_bib5","first-page":"93","article-title":"Recognition and management of behavioral disturbances in dementia","volume":"3","author":"Desai","year":"2001","journal-title":"Prim Care Companion J Clin Psychiatry"},{"key":"10.1016\/j.bja.2023.04.035_bib6","doi-asserted-by":"crossref","first-page":"627","DOI":"10.5177\/ntvt.2014.12.14149","article-title":"Oral health in care-dependent elderly: an inventory in a nursing home in the north of The Netherlands","volume":"121","author":"Hoeksema","year":"2014","journal-title":"Ned Tijdschr Tandheelkd"},{"key":"10.1016\/j.bja.2023.04.035_bib7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1754-4505.1996.tb00837.x","article-title":"Factors influencing nurses\u2019 aides\u2019 provision of oral care for nursing facility residents","volume":"16","author":"Chalmers","year":"1996","journal-title":"Spec Care Dentist"},{"key":"10.1016\/j.bja.2023.04.035_bib8","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1007\/s00784-016-2011-0","article-title":"Oral health status and need for oral care of care-dependent indwelling elderly: from admission to death","volume":"21","author":"Hoeksema","year":"2017","journal-title":"Clin Oral Investig"},{"key":"10.1016\/j.bja.2023.04.035_bib9","first-page":"6","article-title":"Topical review: orofacial pain in dementia patients. A diagnostic challenge","volume":"25","author":"Lobbezoo","year":"2011","journal-title":"J\u00a0Orofac Pain"},{"key":"10.1016\/j.bja.2023.04.035_bib10","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1365-2125.1987.tb03037.x","article-title":"Intravenous midazolam for upper gastrointestinal endoscopy: a study of 800 consecutive cases relating dose to age and sex of patient","volume":"23","author":"Bell","year":"1987","journal-title":"Br J Clin Pharmacol"},{"key":"10.1016\/j.bja.2023.04.035_bib11","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/S0009-9236(99)90084-X","article-title":"The effect of age on the pharmacokinetics and pharmacodynamics of midazolam","volume":"65","author":"Albrecht","year":"1999","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.bja.2023.04.035_bib12","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/S0009-9236(98)90106-0","article-title":"Pharmacokinetics and the pharmacodynamic action of midazolam in young and elderly patients undergoing tooth extraction","volume":"63","author":"Platten","year":"1998","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.bja.2023.04.035_bib13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1097\/00000542-198461010-00006","article-title":"Effect of age, gender, and obesity on midazolam kinetics","volume":"61","author":"Greenblatt","year":"1984","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2023.04.035_bib14","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"J\u00a0Open Source Softw"},{"key":"10.1016\/j.bja.2023.04.035_bib15","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1124\/dmd.115.068601","article-title":"Mechanistic modeling to predict midazolam metabolite exposure from in\u00a0vitro data","volume":"44","author":"Nguyen","year":"2016","journal-title":"Drug Metab Dispos"},{"key":"10.1016\/j.bja.2023.04.035_bib16","series-title":"PubChem compound summary for CID 4192, midazolam","year":"2004"},{"key":"10.1016\/j.bja.2023.04.035_bib17","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1002\/psp4.12422","article-title":"NONMEM tutorial part II: estimation methods and advanced examples","volume":"8","author":"Bauer","year":"2019","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"10.1016\/j.bja.2023.04.035_bib18","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1023\/B:JOPA.0000012998.04442.1f","article-title":"Simultaneous vs. sequential analysis for population PK\/PD data I: best-case performance","volume":"30","author":"Zhang","year":"2003","journal-title":"J\u00a0Pharmacokinet Pharmacodyn"},{"key":"10.1016\/j.bja.2023.04.035_bib19","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1124\/dmd.111.040782","article-title":"Systemic and direct nose-to-brain transport pharmacokinetic model for remoxipride after intravenous and intranasal administration","volume":"39","author":"Stevens","year":"2011","journal-title":"Drug Metab Dispos"},{"key":"10.1016\/j.bja.2023.04.035_bib20","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1023\/A:1012216600170","article-title":"Bispectral index (BIS) and burst suppression: revealing a part of the BIS algorithm","volume":"16","author":"Bruhn","year":"2000","journal-title":"J\u00a0Clin Monit Comput"},{"key":"10.1016\/j.bja.2023.04.035_bib21","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.jocn.2014.11.007","article-title":"Induction of burst suppression or coma using intravenous anesthetics in refractory status epilepticus","volume":"22","author":"Kang","year":"2015","journal-title":"J\u00a0Clin Neurosci"},{"key":"10.1016\/j.bja.2023.04.035_bib22","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1208\/s12248-011-9255-z","article-title":"Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models","volume":"13","author":"Bergstrand","year":"2011","journal-title":"AAPS J"},{"key":"10.1016\/j.bja.2023.04.035_bib23","series-title":"Shiny: web application framework for R","author":"Chang","year":"2021"},{"key":"10.1016\/j.bja.2023.04.035_bib24","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/psp4.12052","article-title":"A\u00a0tutorial on RxODE: simulating differential equation pharmacometric models in R","volume":"5","author":"Wang","year":"2016","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"10.1016\/j.bja.2023.04.035_bib25","unstructured":"Auguie B. gridExtra: miscellaneous functions for \u201cgrid\u201d graphics. R package version 2.3 2017. Available from https:\/\/CRAN.R-project.org\/package=gridExtra (2020)."},{"key":"10.1016\/j.bja.2023.04.035_bib26","series-title":"gridExtra, RStudio: integrated development for R. RStudio","year":"2020"},{"key":"10.1016\/j.bja.2023.04.035_bib27","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1093\/bja\/79.5.575","article-title":"Pharmacokinetics of midazolam given as an intranasal spray to adult surgical patients","volume":"79","author":"Bjorkman","year":"1997","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.bja.2023.04.035_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.eplepsyres.2021.106567","article-title":"Clinical pharmacokinetic and pharmacodynamic profile of midazolam nasal spray","volume":"171","author":"Bouw","year":"2021","journal-title":"Epilepsy Res"},{"key":"10.1016\/j.bja.2023.04.035_bib29","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.yebeh.2017.02.023","article-title":"Pharmacokinetics, pharmacodynamics, and tolerability of USL261, midazolam nasal spray: randomized study in healthy geriatric and non-geriatric adults","volume":"71","author":"Berg","year":"2017","journal-title":"Epilepsy Behav"},{"key":"10.1016\/j.bja.2023.04.035_bib30","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/clpt.2011.316","article-title":"Intranasal midazolam: pharmacokinetics and pharmacodynamics assessed by quantitative EEG in healthy volunteers","volume":"91","author":"Hardmeier","year":"2012","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.bja.2023.04.035_bib31","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1002\/jps.21924","article-title":"Intranasal delivery to the central nervous system: mechanisms and experimental considerations","volume":"99","author":"Dhuria","year":"2010","journal-title":"J\u00a0Pharm Sci"},{"key":"10.1016\/j.bja.2023.04.035_bib32","doi-asserted-by":"crossref","first-page":"288","DOI":"10.18433\/J3NC79","article-title":"Intranasal drug delivery: how, why and what for?","volume":"12","author":"Pires","year":"2009","journal-title":"J\u00a0Pharm Pharm Sci"},{"key":"10.1016\/j.bja.2023.04.035_bib33","first-page":"321","article-title":"A\u00a0pharmacokinetic study of midazolam in dogs: nasal drop vs. atomizer administration","volume":"20","author":"Henry","year":"1998","journal-title":"Pediatr Dent"}],"container-title":["British Journal of Anaesthesia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0007091223002283?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0007091223002283?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T17:16:35Z","timestamp":1762103795000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0007091223002283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["S0007091223002283"],"URL":"https:\/\/doi.org\/10.1016\/j.bja.2023.04.035","relation":{},"ISSN":["0007-0912"],"issn-type":[{"value":"0007-0912","type":"print"}],"subject":[],"published":{"date-parts":[[2023,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Development of a pharmacokinetic and pharmacodynamic model for intranasal administration of midazolam in older adults: a single-site two-period crossover study","name":"articletitle","label":"Article Title"},{"value":"British Journal of Anaesthesia","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bja.2023.04.035","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Ltd on behalf of British Journal of Anaesthesia.","name":"copyright","label":"Copyright"}]}}