دورية أكاديمية
QT Interval Shortening With Isavuconazole: In Vitro and In Vivo Effects on Cardiac Repolarization.
| العنوان: | QT Interval Shortening With Isavuconazole: In Vitro and In Vivo Effects on Cardiac Repolarization. |
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| المؤلفون: | Keirns, J, Desai, A, Kowalski, D, Lademacher, C, Mujais, S, Parker, B, Schneidkraut, MJ, Townsend, R, Wojtkowski, T, Yamazaki, T, Yen, M, Kowey, PR |
| المصدر: | Clinical Pharmacology & Therapeutics; Jun2017, Vol. 101 Issue 6, p782-790, 9p |
| مصطلحات موضوعية: | TRIAZOLE derivatives, CALCIUM channels, ELECTROCARDIOGRAPHY, TACHYCARDIA, CELL polarity, MOXIFLOXACIN, CARDIOTONIC agents |
| مستخلص: | The effects of isavuconazole (active moiety of isavuconazonium sulfate) on cardiac ion channels in vitro and cardiac repolarization clinically were assessed in a phase I, randomized, double-blind study in healthy individuals who received isavuconazole (after 2-day loading dose), at therapeutic or supratherapeutic doses daily for 11 days, moxifloxacin (400 mg q.d.), or placebo. A post-hoc analysis of the phase III SECURE trial assessed effects on cardiac safety. L-type Ca2+ channels were most sensitive to inhibition by isavuconazole. The 50% inhibitory concentrations for ion channels were higher than maximum serum concentrations of nonprotein-bound isavuconazole in vivo. In the phase I study ( n = 161), isavuconazole shortened the QT interval in a dose- and plasma concentration-related manner. There were no serious treatment-emergent adverse events; palpitations and tachycardia were observed in placebo and supratherapeutic isavuconazole groups; no cardiac safety signals were detected in the SECURE study ( n = 257). Isavuconazole was associated with a shortened cardiac QT interval. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: | Complementary Index |
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