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Effects of the Fluoroquinolones Moxifloxacin and Levofloxacin on the QT Subintervals: Sex Differences in Ventricular Repolarization.

Täubel, J; Prasad, K; Rosano, G; Ferber, G; Wibberley, H; Cole, ST; Van Langenhoven, L; Fernandes, S; Djumanov, D; Sugiyama, A (2019) Effects of the Fluoroquinolones Moxifloxacin and Levofloxacin on the QT Subintervals: Sex Differences in Ventricular Repolarization. J Clin Pharmacol, 60 (3). pp. 400-408. ISSN 1552-4604 https://doi.org/10.1002/jcph.1534
SGUL Authors: Rosano, Giuseppe Massimo Claudio

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Abstract

Women are associated with longer electrocardiographic QT intervals and increased proarrhythmic risks of QT-prolonging 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 mg) and levofloxacin (1000 and 1500 mg) on QT subintervals using algorithms for measurement of J-Tpeak and Tpeak -Tend intervals. Concentration-effect 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-Tpeak c. Levofloxacin had little effect on J-Tpeak c. For moxifloxacin, the concentration-effect modeling showed a greater effect for women on QTcF and J-Tpeak c, whereas for levofloxacin the inverse was true: women had smaller QTcF and J-Tpeak c effects. The different patterns in repolarization after administration of both drugs suggested a sex difference, which may be related to the combined IKs and IKr inhibitory properties of moxifloxacin versus IKr suppression only of levofloxacin. The equipotent inhibition of IKs and IKr appears to affect women more than men. Sex hormones are known to influence cardiac ion channel expression and differences in QT duration. Differences in IKr and IKs balances, influenced by sex hormones, may explain the results. These results support the impact of sex differences on the cardiac safety assessment of drugs.

Item Type: Article
Additional Information: © 2019 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Keywords: IKr, IKs, J-Tpeak, Tpeak-Tend, ion channel effects, levofloxacin, moxifloxacin, 1115 Pharmacology And Pharmaceutical Sciences, Pharmacology & Pharmacy
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: J Clin Pharmacol
ISSN: 1552-4604
Language: eng
Dates:
DateEvent
21 October 2019Published Online
26 September 2019Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
PubMed ID: 31637733
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/111380
Publisher's version: https://doi.org/10.1002/jcph.1534

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