{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:41:14Z","timestamp":1790185274695,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T00:00:00Z","timestamp":1602460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>\n                    Remimazolam is an ultra\u2010short acting benzodiazepine under development for procedural sedation and general anesthesia. Population pharmacokinetic analysis (PopPK) was conducted for remimazolam with arterial and venous samples previously, but results were limited by arterial\u2010venous concentration differences and inaccurate central volume of distribution (V1) estimates. A new model was developed to describe covariate effects after accounting for arterial\u2010venous differences. Arterial and venous plasma concentration\u2010time data from 11 clinical trials were pooled for PopPK. Data from two constant\u2010rate infusion studies were used to account for venous\u2010to\u2010arterial (VtoA) ratio within residual error and to accurately estimate V1. V1 and VtoA ratio from the pilot model were applied to the full dataset, where the optimal fixed\/random effects and covariates were assessed. VtoA ratio was described using a maximum effect (E\n                    <jats:sub>max<\/jats:sub>\n                    ) model during infusion and as a constant postdose. V1 was estimated as 4.83\u00a0L for a 70\u00a0kg subject and interindividual variability (IIV) on V1 could only be estimated in studies with early concentrations. IIV on clearance was low (22.9%). Covariates included effects of sex on clearance (women 10%\u00a0&gt;\u00a0men), and race on clearance and steady\u2010state volume of distribution (African Americans 16%\u00a0&lt;\u00a0other races). Arterial\u2010venous concentration differences were best described using an E\n                    <jats:sub>max<\/jats:sub>\n                    model during infusion with a constant ratio after infusion, resulting in low residual error (20.7%). There are no clinically relevant dose adjustments needed for any covariates based on pharmacokinetic differences.\n                  <\/jats:p>","DOI":"10.1111\/cts.12875","type":"journal-article","created":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T17:14:10Z","timestamp":1602522850000},"page":"326-334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Population Pharmacokinetics of Remimazolam in Procedural Sedation With Nonhomogeneously Mixed Arterial and Venous Concentrations"],"prefix":"10.1111","volume":"14","author":[{"given":"Jie","family":"Zhou","sequence":"first","affiliation":[{"name":"Nuventra Pharma Sciences  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Curd","sequence":"additional","affiliation":[{"name":"Nuventra Pharma Sciences  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren L.","family":"Lohmer","sequence":"additional","affiliation":[{"name":"Nuventra Pharma Sciences  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Ossig","sequence":"additional","affiliation":[{"name":"PAION UK Ltd.  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Schippers","sequence":"additional","affiliation":[{"name":"PAION UK Ltd.  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Stoehr","sequence":"additional","affiliation":[{"name":"PAION UK Ltd.  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Schmith","sequence":"additional","affiliation":[{"name":"Nuventra Pharma Sciences  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,12]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e318241f68a"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.01.028"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinane.2020.109899"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2199\/jjsca.34.860"},{"key":"e_1_2_10_5_1","unstructured":"ONO\u20102745IVU007.An open\u2010label single\u2010dose intravenous administration study to compare the pharmacokinetics and safety of ONO\u20102745\/CNS 7056 in subjects with chronic hepatic impairment with matching healthy subjects (NCT01790607).2014<https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01790607>."},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2015.05.267"},{"key":"e_1_2_10_7_1","first-page":"543","article-title":"Efficacy and safety of remimazolam versus propofol for general anesthesia: a multicenter, single\u2010blind, randomized, parallel\u2010group, phase IIb\/III trial","volume":"34","author":"Doi M.","year":"2020","journal-title":"J. Clin. Anesth."},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00540-020-02776-w"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e3182a705ae"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gie.2015.08.062"},{"key":"e_1_2_10_11_1","unstructured":"Petersen K.U.Pre\u2010clinical profile of remimazolam and pharmacokinetics.3rd Annual Meeting of the Japan Society for Clinical Anesthesia. (2017)."},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199710000-00024"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00140.2009"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000003103"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gie.2018.04.2351"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2018.09.015"},{"key":"e_1_2_10_17_1","unstructured":"CNS7056\u2010015.A study evaluating the safety and efficacy of remimazolam (CNS7056) compared to placebo and midazolam in ASA class III or IV patients undergoing colonoscopy (NCT02532647)(2017) <https:\/\/clinicaltrials.gov\/ct2\/show\/results\/NCT02532647>."},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2165\/00044011-199509030-00001"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12875","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.12875","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12875","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T02:06:31Z","timestamp":1693620391000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.12875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,12]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1111\/cts.12875"],"URL":"https:\/\/doi.org\/10.1111\/cts.12875","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.738969627.793584540","asserted-by":"object"}]},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,12]]},"assertion":[{"value":"2020-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}