{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:08:04Z","timestamp":1788772084033,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012150","name":"Shanghai Leading Academic Discipline Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204544"],"award-info":[{"award-number":["82204544"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471282"],"award-info":[{"award-number":["82471282"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["associationofanaesthetists-publications.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anaesthesia"],"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The pharmacological profile of remimazolam makes it particularly suitable for patients living with obesity. However, how its pharmacokinetics are influenced by varying degrees of obesity and obstructive sleep apnoea severity remains unclear. This study aimed to characterise remimazolam pharmacokinetics in volunteers living with different levels of obesity and obstructive sleep apnoea.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Stepwise escalating infusion of remimazolam was administered until five consecutive modified observer's assessment of alertness and sedation scores of 1 were recorded. Arterial blood samples were collected before infusion, at each infusion rate adjustment step, 5\u2009minutes after each adjustment and several time points post\u2010infusion discontinuation. Drug concentrations were quantified using ultra\u2010high\u2010performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. A joint population pharmacokinetic model characterising remimazolam and its metabolite CNS7054 was developed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Forty\u2010four adult volunteers, 30 (68.2%) with obstructive sleep apnoea, were studied. Remimazolam pharmacokinetics were best described by a three\u2010compartment model; a one\u2010compartment model with transit compartment described CNS7054. External validation confirmed robust prediction performance. Clearance of remimazolam was high (1.09\u2009l.min\n                      <jats:sup>\u20101<\/jats:sup>\n                      , relative standard error\u2009=\u20094%). Total body weight significantly affected clearance and metabolite volume of distribution. No other covariates, including obstructive sleep apnoea severity, had significant impact. In patients living with class 2\/3 obesity, context\u2010sensitive half\u2010time after a 4\u2010h infusion was short (4.02\u2009min). Dosing based on lean\/ideal body weight for induction, or adjusted body weight for maintenance, in patients living with class 2\/3 obesity yielded pharmacokinetic profiles comparable with those achieved with total body weight dosing in normal weight patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Body size significantly alters remimazolam pharmacokinetics and individualised weight\u2010based dosing is essential for populations with obesity. Obstructive sleep apnoea severity does not affect drug disposition; however, its pharmacodynamic effects require further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/anae.70367","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:11:30Z","timestamp":1788768690000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of obesity on pharmacokinetics and drug dosing of remimazolam in patients with obstructive sleep apnoea"],"prefix":"10.1111","author":[{"given":"Xin\u2010Yi","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Wen","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology Eye &amp; ENT Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Fei","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine The Chinese University of Hong Kong  Hong Kong Special Administrative Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Jing","family":"Huang","sequence":"additional","affiliation":[{"name":"ENT institute and Department of Otorhinolaryngology Eye &amp; ENT Hospital of Fudan University  Shanghai China"},{"name":"Sleep Medicine Centre, Eye &amp; ENT Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences Fudan University  Shanghai China"},{"name":"Key Laboratory of Smart Drug Delivery Ministry of Education  Shanghai China"},{"name":"National Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology Eye &amp; ENT Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Li","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology Eye &amp; ENT Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang\u2010Shuang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology Eye &amp; ENT Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Xian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology Eye &amp; ENT Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology Eye &amp; ENT Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences Fudan University  Shanghai China"},{"name":"National Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001496\u20103"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2004.07.002"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0000000000005444"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.14639\/0392\u2010100x\u2010n1100"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.104"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3238\/arztebl.m2023.0216"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(23)02750\u20102"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(21)00045\u20100"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.S384155"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ohn.387"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1124743"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/aln.0000000000003103"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e318241f68a"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000005195"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/aco.0000000000001280"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aeq312"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1411856"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.4240\/wjgs.v16.i5.1320"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00540\u2010022\u201003079\u2010y"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.6506"},{"key":"e_1_2_6_22_1","unstructured":"World Health Organization. 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