{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:03:57Z","timestamp":1790687037186,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T00:00:00Z","timestamp":1571616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Women are associated with longer electrocardiographic QT intervals and increased proarrhythmic risks of QT\u2010prolonging drugs. The purpose of this study was to characterize the differences in cardiac electrophysiology between moxifloxacin and levofloxacin in men and women and to assess the balance of inward and outward currents through the analysis of QT subintervals. Data from 2 TQT studies were used to investigate the impact of moxifloxacin (400\u00a0mg) and levofloxacin (1000 and 1500 mg) on QT subintervals using algorithms for measurement of J\u2010T<jats:sub>peak<\/jats:sub> and T<jats:sub>peak<\/jats:sub>\u2010T<jats:sub>end<\/jats:sub> intervals. Concentration\u2010effect analyses were performed to establish potential relationships between the ECG effects and the concentrations of the 2 fluoroquinolones. Moxifloxacin was shown to be a more potent prolonger of QT interval corrected by Fredericia (QTcF) and had a pronounced effect on J\u2010T<jats:sub>peak<\/jats:sub>c. Levofloxacin had little effect on J\u2010T<jats:sub>peak<\/jats:sub>c. For moxifloxacin, the concentration\u2010effect modeling showed a greater effect for women on QTcF and J\u2010T<jats:sub>peak<\/jats:sub>c, whereas for levofloxacin the inverse was true: women had smaller QTcF and J\u2010T<jats:sub>peak<\/jats:sub>c effects. The different patterns in repolarization after administration of both drugs suggested a sex difference, which may be related to the combined I<jats:sub>Ks<\/jats:sub> and I<jats:sub>Kr<\/jats:sub> inhibitory properties of moxifloxacin versus I<jats:sub>Kr<\/jats:sub> suppression only of levofloxacin. The equipotent inhibition of I<jats:sub>Ks<\/jats:sub> and I<jats:sub>Kr<\/jats:sub> appears to affect women more than men. Sex hormones are known to influence cardiac ion channel expression and differences in QT duration. Differences in I<jats:sub>Kr<\/jats:sub> and I<jats:sub>Ks<\/jats:sub> balances, influenced by sex hormones, may explain the results. These results support the impact of sex differences on the cardiac safety assessment of drugs.<\/jats:p>","DOI":"10.1002\/jcph.1534","type":"journal-article","created":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T05:21:16Z","timestamp":1571721676000},"page":"400-408","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Effects of the Fluoroquinolones Moxifloxacin and Levofloxacin on the QT Subintervals: Sex Differences in Ventricular Repolarization"],"prefix":"10.1002","volume":"60","author":[{"given":"J\u04e7rg","family":"T\u00e4ubel","sequence":"first","affiliation":[{"name":"Richmond Pharmacology Ltd St George's, University of London Cranmer Terrace  London UK"},{"name":"Cardiovascular and Cell Sciences Research Institute St George's, University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Prasad","sequence":"additional","affiliation":[{"name":"Medicines and Healthcare Products Regulatory Agency Department of Health and Social Care  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Rosano","sequence":"additional","affiliation":[{"name":"Cardiovascular and Cell Sciences Research Institute St George's, University of London  London UK"},{"name":"Centre of Clinical and Experimental Medicine IRCCS San Raffaele  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Ferber","sequence":"additional","affiliation":[{"name":"Statistik Georg Ferber GmbH Cagliostrostrasse  Riehen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Wibberley","sequence":"additional","affiliation":[{"name":"Richmond Pharmacology Ltd St George's, University of London Cranmer Terrace  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Thomas","family":"Cole","sequence":"additional","affiliation":[{"name":"Richmond Pharmacology Ltd St George's, University of London Cranmer Terrace  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leen","family":"Van Langenhoven","sequence":"additional","affiliation":[{"name":"Richmond Pharmacology Ltd St George's, University of London Cranmer Terrace  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Richmond Pharmacology Ltd St George's, University of London Cranmer Terrace  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilshat","family":"Djumanov","sequence":"additional","affiliation":[{"name":"Richmond Pharmacology Ltd St George's, University of London Cranmer Terrace  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine Toho University  Ota\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.205"},{"issue":"7","key":"e_1_2_8_3_1","first-page":"690","article-title":"Sex differences in the evolution of the electrocardiographic QT interval with age","volume":"8","author":"Rautaharju PM","year":"1992","journal-title":"Can J Cardiol."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1067\/mhj.2000.109918"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2010.04.002"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2014.07.010"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000033596.21845.D8"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(98)00523-2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.22.8.663.33201"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.21.3.301.34206"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/49.4.593"},{"issue":"3","key":"e_1_2_8_12_1","first-page":"806","article-title":"Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics","volume":"296","author":"Anderson ME","year":"2001","journal-title":"J Pharmacol Exp Ther."},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.21.20.1468.34482"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706678"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2016.03.009"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.33"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010381498"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011398361"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.59.1.122"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2009.03595.x"},{"issue":"2","key":"e_1_2_8_21_1","first-page":"106","article-title":"Effect of single 500 mg iv levofloxacin dose on QT interval in healthy subjects","volume":"57","author":"Sugiyama A","year":"2009","journal-title":"Jpn J Chemother."},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2018.01.009"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2012.04190.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jelectrocard.2008.07.027"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1542-474X.2008.00264.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.155"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.238"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9558-5"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1159\/000334441"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-020974"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00429-1"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1993.03510210076031"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)90867-3"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.10.1322"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.04.008"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.523217"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)80781-4"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.702407"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.150367"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1542-474X.2004.94580.x"}],"updated-by":[{"DOI":"10.1002\/jcph.1857","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000}}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1534","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.1534","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1534","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T23:27:26Z","timestamp":1693956446000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,21]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1002\/jcph.1534"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1534","archive":["Portico"],"relation":{"correction":[{"id-type":"doi","id":"10.1002\/jcph.1857","asserted-by":"object"}]},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,21]]},"assertion":[{"value":"2019-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}