Effects of the Fluoroquinolones Moxifloxacin and Levofloxacin on the QT Subintervals: Sex Differences in Ventricular Repolarization
| Autor: | Sara Fernandes, Georg Ferber, Samuel Thomas Cole, Giuseppe M.C. Rosano, Dilshat Djumanov, Helen Wibberley, Krishna Prasad, Atsushi Sugiyama, J. Täubel, Leen Van Langenhoven |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Ventricular Repolarization Potassium Channels IKr Editor's Choice: Pharmacovigilance Action Potentials Qt duration IKs 030226 pharmacology & pharmacy QT interval J‐Tpeak Electrocardiography 03 medical and health sciences 0302 clinical medicine Double-Blind Method Moxifloxacin Levofloxacin Internal medicine medicine Humans Repolarization Pharmacology (medical) Gonadal Steroid Hormones Retrospective Studies Pharmacology Sex Characteristics levofloxacin Cross-Over Studies Cardiac electrophysiology business.industry Tpeak‐Tend Correction Heart Healthy Volunteers Anti-Bacterial Agents Long QT Syndrome 030220 oncology & carcinogenesis Cardiology Female Tpeak tend Calcium Channels ion channel effects moxifloxacin business Algorithms medicine.drug |
| Zdroj: | Journal of Clinical Pharmacology J Clin Pharmacol |
| ISSN: | 1552-4604 0091-2700 |
| DOI: | 10.1002/jcph.1534 |
| Popis: | 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‐Tpeakc. Levofloxacin had little effect on J‐Tpeakc. For moxifloxacin, the concentration‐effect modeling showed a greater effect for women on QTcF and J‐Tpeakc, whereas for levofloxacin the inverse was true: women had smaller QTcF and J‐Tpeakc 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. |
| Databáze: | OpenAIRE |
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