{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T15:37:16Z","timestamp":1769269036715,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,10,14]],"date-time":"2015-10-14T00:00:00Z","timestamp":1444780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ketoconazole is listed among drugs that prolong<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>interval and may increase the risk of torsade de pointes, a severe ventricular arrhythmia. This compound has recently been approved for treatment of Cushing's syndrome, a severe endocrine disorder. These patients harbour several risk factors for prolonged<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>interval, for example hypokalaemia and left ventricular hypertrophy, but no study has evaluated whether administration of ketoconazole affects their<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>interval. The aim of this study was to assess the<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>interval in patients with Cushing's disease during long\u2010term administration of ketoconazole. Electrocardiograms from 15 patients with Cushing's disease (12 women, 3 men, age: 37.8 \u00b1 2.66 years) on ketoconazole treatment (100 mg\u2013800 mg qd) for 1 month to 12 years were reviewed retrospectively.<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>interval was measured and corrected for heart rate (<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>c). Measurements before and during ketoconazole treatment were compared and any abnormal<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>c value recorded. Concurrent medical therapies were also documented. On average,<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>c was superimposable before and during ketoconazole treatment (393.2 \u00b1 7.17<jats:italic>versus<\/jats:italic>403.3 \u00b1 6.05 msec. in women; 424.3 \u00b1 23.54<jats:italic>versus<\/jats:italic>398.0 \u00b1 14.93 msec. in men, N.S.).<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>c normalized on ketoconazole in one man with prolonged<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>c prior to treatment; no abnormal<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>c was observed in any other patient during the entire observation period, even during concurrent treatment with other<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>\u2010prolonging drugs. In conclusion, long\u2010term ketoconazole administration does not appear to be associated with significant prolongation of<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>interval in patients with Cushing's disease.<jats:styled-content style=\"fixed-case\">ECG<\/jats:styled-content>monitoring can follow recommendations drawn for other low\u2010risk<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>\u2010prolonging drugs with attention to specific risk factors, for example hypokalaemia and drug interactions.<\/jats:p>","DOI":"10.1111\/bcpt.12490","type":"journal-article","created":{"date-parts":[[2015,9,19]],"date-time":"2015-09-19T15:19:00Z","timestamp":1442675940000},"page":"279-283","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["No Untoward Effect of Long\u2010Term Ketoconazole Administration on Electrocardiographic QT Interval in Patients with Cushing's Disease"],"prefix":"10.1111","volume":"118","author":[{"given":"Martina","family":"De Martin","sequence":"first","affiliation":[{"name":"Neuroendocrinology Research Laboratory IRCCS Istituto Auxologico Italiano Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola Maria","family":"Toja","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolic Diseases IRCCS Istituto Auxologico Italiano Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karine","family":"Goulene","sequence":"additional","affiliation":[{"name":"Department of Geriatrics and Cardiovascular Medicine IRCCS Istituto Auxologico Italiano Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piero","family":"Radaelli","sequence":"additional","affiliation":[{"name":"Neuroendocrinology Research Laboratory IRCCS Istituto Auxologico Italiano Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Cavagnini","sequence":"additional","affiliation":[{"name":"Neuroendocrinology Research Laboratory IRCCS Istituto Auxologico Italiano Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Stramba\u2010Badiale","sequence":"additional","affiliation":[{"name":"Department of Geriatrics and Cardiovascular Medicine IRCCS Istituto Auxologico Italiano Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Pecori Giraldi","sequence":"additional","affiliation":[{"name":"Neuroendocrinology Research Laboratory IRCCS Istituto Auxologico Italiano Milan Italy"},{"name":"Department of Clinical Sciences and Community Health University of Milan Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,10,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra032426"},{"key":"e_1_2_5_3_1","unstructured":"Clinical Evaluation of QT\/QTc interval prolongation and proarrhythmic potential of non\u2010antiarrhythmic drugs.http:\/\/www.fda.gov\/downloads\/drugs\/guidancecomplianceregulatoryinformation\/guidances\/ucm073153.pdf\/(last accessed on 30 October 2005)."},{"key":"e_1_2_5_4_1","unstructured":"Assessing risk of drugs that prolong the QT interval and cause arrhythmias.https:\/\/www.crediblemeds.org\/new-drug-list\/\/ (last accessed on 30 June 2015)."},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12227"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-199818020-00001"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2007.00017.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198709243171307"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3628"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.9.14.2423"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2734"},{"key":"e_1_2_5_12_1","unstructured":"Ketoconazole HRA recommended for approval in Cushing's syndrome.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Press_release\/2014\/09\/WC500173638.pdf\/(last accessed on 26 September 2014)."},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1271628"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.2002.3274"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.88.2.782"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(94)90267-4"},{"key":"e_1_2_5_17_1","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1001\/jama.1993.03500120051025","article-title":"Terfenadine\u2010ketoconazole interaction. 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