{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T20:09:13Z","timestamp":1778702953720,"version":"3.51.4"},"reference-count":13,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T00:00:00Z","timestamp":1531094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Australian and New Zealand Clinical Trials Registry","award":["ACTRN12615000225516"],"award-info":[{"award-number":["ACTRN12615000225516"]}]}],"content-domain":{"domain":["associationofanaesthetists-publications.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anaesthesia"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Midazolam is one of many bitter drugs where provision of a suitable oral paediatric formulation, particularly in the pre\u2010anaesthetic setting, remains a challenge. To overcome this problem, a novel chocolate\u2010based tablet formulation has been developed with positive pre\u2010clinical results. To further investigate the potential of this formulation, 150 children aged 3\u201316 years who were prescribed midazolam as a premedication were randomly assigned to receive 0.5 mg.kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    either as the novel formulation or an intravenous solution given orally, which is the current standard at our institution. Tolerability was assessed by each child, parent and nurse using a 5\u2010point facial hedonic scale and efficacy was determined as the time to onset of sedation. Blood samples for midazolam and 1\u2010hydroxymidazolam levels were analysed using high\u2010performance liquid chromatography. Population pharmacokinetics were evaluated using non\u2010linear mixed effects modelling. The novel formulation had significantly improved tolerability scores from children, parents and nurses (all p &lt; 0.001). Time to effect was not different between the groups (p = 0.140). The pharmacokinetics of midazolam and 1\u2010hydroxymidazolam were able to be modelled simultaneously. The novel formulation was subject to a higher estimated first\u2010pass metabolism compared with the intravenous solution (8.6% vs. 5.0%) and a significantly lower relative bioavailability of 82.1% (p = 0.013), with no other significant differences. Exposure relative to dose was in the range previously reported for midazolam syrup. We conclude that the novel chocolate\u2010based formulation of midazolam provides improved tolerability while remaining efficacious with suitable pharmacokinetics when used as a premedicant for children.\n                  <\/jats:p>","DOI":"10.1111\/anae.14318","type":"journal-article","created":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T07:45:50Z","timestamp":1531122350000},"page":"1469-1477","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A novel, palatable paediatric oral formulation of midazolam: pharmacokinetics, tolerability, efficacy and safety"],"prefix":"10.1111","volume":"73","author":[{"given":"S.","family":"Salman","sequence":"first","affiliation":[{"name":"Faculty of Health and Medical Sciences Medical School University of Western Australia Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. K. Y.","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Pharmacy Faculty of Health and Medical Sciences School of Allied Health University of Western Australia Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. C.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Telethon Kids Institute University of Western Australia Perth Australia"},{"name":"School of Pharmacy and Biomedical Sciences Curtin University Perth Australia"},{"name":"Department of Pharmacy Princess Margaret Hospital for Children Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. N.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Pharmacy Faculty of Health and Medical Sciences School of Allied Health University of Western Australia Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Sommerfield","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Pain Management Princess Margaret Hospital for Children Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Slevin","sequence":"additional","affiliation":[{"name":"Telethon Kids Institute University of Western Australia Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. Y.","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Pharmacy Faculty of Health and Medical Sciences School of Allied Health University of Western Australia Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. S.","family":"von Ungern Sternberg","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences Medical School University of Western Australia Perth Australia"},{"name":"Department of Anaesthesia and Pain Management Princess Margaret Hospital for Children Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,7,9]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"1072","article-title":"A report from the pediatric formulations task force: perspectives on the state of child\u2010friendly oral dosage forms","volume":"15","author":"Zajicek A","year":"2013","journal-title":"American Association of Pharmaceutical Scientists Journal"},{"key":"e_1_2_6_3_1","first-page":"20","article-title":"1902 \u2044 2006 of the European Parliament and of the Council of 20 December 2006 amending Regulation 1901 \u2044 2006 on medicinal products for paediatric use","volume":"2006","author":"European Parliament and the Council of the European Union Regulation (EC) n","year":"1902","journal-title":"Official Journal of the European Union"},{"key":"e_1_2_6_4_1","volume-title":"Reflection paper: formulations of choice for the paediatric population","author":"Committee for Medicinal Products for Human Use","year":"2006"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2008.02462.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1213\/00000539-200302000-00017","article-title":"Midazolam premedication in children: a comparison of two oral dosage formulations on sedation score and plasma midazolam levels","volume":"96","author":"Brosius KK","year":"2003","journal-title":"Anesthesia and Analgesia"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2017.10.060"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2007.12.033"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2007.02.034"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.24.25"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-007-9066-0"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/00912700122012832"},{"key":"e_1_2_6_13_1","first-page":"371","article-title":"Handling data below the limit of quantification in mixed effect models","volume":"11","author":"Bergstrand M","year":"2009","journal-title":"American Association of Pharmaceutical Scientists Journal"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00679782"}],"container-title":["Anaesthesia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fanae.14318","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/associationofanaesthetists-publications.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/anae.14318","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T20:55:03Z","timestamp":1761684903000},"score":1,"resource":{"primary":{"URL":"https:\/\/associationofanaesthetists-publications.onlinelibrary.wiley.com\/doi\/10.1111\/anae.14318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,9]]},"references-count":13,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1111\/anae.14318"],"URL":"https:\/\/doi.org\/10.1111\/anae.14318","archive":["Portico"],"relation":{},"ISSN":["0003-2409","1365-2044"],"issn-type":[{"value":"0003-2409","type":"print"},{"value":"1365-2044","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,9]]},"assertion":[{"value":"2018-04-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}