Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8532814 | Journal of Pharmacological Sciences | 2018 | 8 Pages |
Abstract
Effects of moxifloxacin on QTc as well as proarrhythmic surrogate markers including J-Tpeakc, Tpeak-Tend and short-term variability (STV) of repolarization were examined by using both standard E14 time-based evaluation and exposure-response modeling. The study was conducted with a single-blind, randomized, single-dose, placebo-controlled and two-period cross-over design in healthy Filipino subjects. QT interval was corrected by Fridericia's formula (QTcF). In the E14 time-based evaluation of ECG data, the largest ÎÎQTcF with 90% confidence interval was 14.1 ms (11.2-16.9) with Cmax of 3.39 μg/mL at 3 h post-dose (n = 69; male: 35, female: 34), indicating a positive effect on the QTcF. Moxifloxacin significantly increased the ÎÎJ-Tpeakc and ÎÎTpeak-Tend, whereas the ÎÎSTV was not altered. Meanwhile in the exposure-response modeling of the same ECG data, the slope of moxifloxacin plasma concentration-ÎÎQTcF relationship was 4.84 ms per μg/mL and the predicted ÎÎQTcF with 90% confidence interval was 13.8 ms (13.1-15.1) at Cmax, also indicating a positive effect on the QTcF. Importantly, results in each proarrhythmic surrogate marker obtained by the exposure-response modeling also showed high similarity to those obtained by the E14 statistical evaluation. Thus, these results of moxifloxacin may become a guide to estimate proarrhythmic potential of new chemical entities.
Keywords
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Pharmacology, Toxicology and Pharmaceutical Science
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Authors
Suchitra Matsukura, Yuji Nakamura, Kiyotaka Hoshiai, Takashi Hayashi, Tadashi Koga, Ai Goto, Koki Chiba, Nur Jaharat Lubna, Mihoko Hagiwara-Nagasawa, Hiroko Izumi-Nakaseko, Kentaro Ando, Atsuhiko T. Naito, Atsushi Sugiyama,