{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:10:53Z","timestamp":1790615453802,"version":"4.1.0"},"reference-count":10,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T00:00:00Z","timestamp":1584921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Remimazolam is a new, ultra\u2010short\u2010acting benzodiazepine developed for intravenous (IV) use during procedural sedation and in general anaesthesia. Two trials were conducted to characterize its effects on cardiac repolarization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A thorough QT\/QTc (TQT) study assessed electrocardiography effects of therapeutic and supratherapeutic doses of remimazolam and midazolam. To investigate whether RR\u2010QT hysteresis effects due to rapid heart rate changes might have confounded the QTc assessments in the TQT trial, a second trial used continuous IV remimazolam infusion to achieve stable heart rates during periods of stable remimazolam plasma concentration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During the TQT, both compounds produced a 10\u201320\u2010beats\/min increase in heart rate within 30 seconds, persisting for 5\u201310 minutes. Within 30 seconds, the upper bound of the 2\u2010sided 90% confidence interval for the placebo\u2010corrected change from baseline for QTcI (\u0394\u0394QTcI) exceeded 10 ms for both doses of remimazolam (\u0394\u0394QTcI 7.2 [3.2, 11.2] ms for the 10 mg dose and 10.4 [6.5, 14.3] ms for the 20 mg dose) as well as for the 7.5\u2010mg dose of midazolam (8.2 [4.4, 12.1] ms). At 2 minutes after IV bolus, the upper bound of the 2\u2010sided 90% confidence interval for \u0394\u0394QTcI exceeded 10 ms only for the remimazolam 20\u2010mg dose (6.3 [2.3, 10.2] ms). During the second study, during periods of stable heart rate, remimazolam had no clinically significant effect on QTc (peak \u0394\u0394QTcI 3.4 [\u22121.1, 7.6] ms).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Remimazolam does not prolong cardiac repolarization (QTc). The methods reported here may allow assessment of the QTc effects of other drugs given by IV bolus.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14270","type":"journal-article","created":{"date-parts":[[2020,3,7]],"date-time":"2020-03-07T03:59:37Z","timestamp":1583553577000},"page":"1600-1609","source":"Crossref","is-referenced-by-count":37,"title":["Potential strategy for assessing QT\/QTc interval for drugs that produce rapid changes in heart rate: Electrocardiographic assessment of the effects of intravenous remimazolam on cardiac repolarization"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0333-9045","authenticated-orcid":false,"given":"Robert B.","family":"Kleiman","sequence":"first","affiliation":[{"name":"eResearch Technology  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borje","family":"Darpo","sequence":"additional","affiliation":[{"name":"eResearch Technology  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Thorn","sequence":"additional","affiliation":[{"name":"Statistical Resources  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7162-5786","authenticated-orcid":false,"given":"Thomas","family":"Stoehr","sequence":"additional","affiliation":[{"name":"Paion Germany GmbH  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Schippers","sequence":"additional","affiliation":[{"name":"Paion Germany GmbH  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,23]]},"reference":[{"issue":"56","key":"e_1_2_13_2_1","first-page":"43","article-title":"Population pharmacokinetics of remimazolam after continuous infusion in volunteers","volume":"35","author":"Ihmsen H","year":"2018","journal-title":"Eur J Anaesthesiol"},{"key":"e_1_2_13_3_1","unstructured":"ICH Guideline E14. May 2005. Available at:http:\/\/www.ich.org\/fileadmin\/Public_Web_Site\/ICH_Products\/Guidelines\/Efficacy\/E14\/E14_Guideline.pdf."},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12684"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010381498"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2012.02.023"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00860.2001"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00625.2008"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12201"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113706"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-016-0406-0"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.14270","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.14270","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.14270","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.14270","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T16:16:41Z","timestamp":1693930601000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.14270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,23]]},"references-count":10,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1111\/bcp.14270"],"URL":"https:\/\/doi.org\/10.1111\/bcp.14270","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,23]]}}}