{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:45:26Z","timestamp":1791402326620,"version":"4.3.3"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,2,13]],"date-time":"2017-02-13T00:00:00Z","timestamp":1486944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>\n                    The effects of isavuconazole (active moiety of isavuconazonium sulfate) on cardiac ion channels\n                    <jats:italic>in vitro<\/jats:italic>\n                    and cardiac repolarization clinically were assessed in a phase I, randomized, double\u2010blind study in healthy individuals who received isavuconazole (after 2\u2010day loading dose), at therapeutic or supratherapeutic doses daily for 11 days, moxifloxacin (400\u2009mg q.d.), or placebo. A post\u2010hoc analysis of the phase III SECURE trial assessed effects on cardiac safety. L\u2010type Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels were most sensitive to inhibition by isavuconazole. The 50% inhibitory concentrations for ion channels were higher than maximum serum concentrations of nonprotein\u2010bound isavuconazole\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In the phase I study (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009161), isavuconazole shortened the QT interval in a dose\u2010 and plasma concentration\u2010related manner. There were no serious treatment\u2010emergent adverse events; palpitations and tachycardia were observed in placebo and supratherapeutic isavuconazole groups; no cardiac safety signals were detected in the SECURE study (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009257). Isavuconazole was associated with a shortened cardiac QT interval.\n                  <\/jats:p>","DOI":"10.1002\/cpt.620","type":"journal-article","created":{"date-parts":[[2017,1,11]],"date-time":"2017-01-11T03:28:53Z","timestamp":1484105333000},"page":"782-790","source":"Crossref","is-referenced-by-count":79,"title":["QT Interval Shortening With Isavuconazole:\n                    <i>In Vitro<\/i>\n                    and\n                    <i>In Vivo<\/i>\n                    Effects on Cardiac Repolarization"],"prefix":"10.1111","volume":"101","author":[{"given":"J","family":"Keirns","sequence":"first","affiliation":[{"name":"Astellas Pharma Global Development, Inc Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Desai","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Lademacher","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Mujais","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Parker","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MJ","family":"Schneidkraut","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Townsend","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Wojtkowski","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Yen","sequence":"additional","affiliation":[{"name":"PAREXEL Glendale California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PR","family":"Kowey","sequence":"additional","affiliation":[{"name":"Lankenau Medical Center and Institute for Medical Research, Main Line Health System Wynnewood Pennsylvania USA"},{"name":"Jefferson Medical College Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,13]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.003723"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/508873"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/423275"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-6757(00)90027-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0022-3565(24)37646-3","article-title":"Blockade of HERG and Kv1.5 by ketoconazole","volume":"286","author":"Dumaine R.","year":"1998","journal-title":"J. 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Accessed March 10 2015."},{"key":"e_1_2_9_13_1","unstructured":"European Medicines Agency.Cresemba (isavuconazole). <http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/medicines\/human\/medicines\/002734\/human_med_001907.jsp&mid=WC0b01ac058001d124> (2015). Accessed November 11 2015."},{"key":"e_1_2_9_14_1","first-page":"163","article-title":"Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections","volume":"6","author":"Falci D.R.","year":"2013","journal-title":"Infect. Drug Resist."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01159-9"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)00071-2"},{"key":"e_1_2_9_17_1","unstructured":"Perfect J.et al.Outcomes safety and tolerability of isavuconazole for the treatment of invasive fungal disease (phase 3 VITAL trial). In International Society for Human and Animal Mycology \u2013 2015 Congress."},{"key":"e_1_2_9_18_1","article-title":"Pharmacokinetic evaluation of CYP3A4\u2010mediated drug\u2010drug interactions of isavuconazole with rifampin, ketoconazole, midazolam, and ethinyl estradiol\/norethindrone in healthy adults","author":"Townsend R","year":"2016","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"e_1_2_9_19_1","article-title":"Pharmacokinetic assessment of drug\u2010drug interactions of isavuconazole with the immunosuppressants cyclosporine, mycophenolic acid, prednisolone, sirolimus, and tacrolimus in healthy adults","author":"Groll A.H.","year":"2016","journal-title":"Clin. Pharmacol. 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