Int J Clin Pharmacol Ther. 2021 Jan;59(1):63-70. doi: 10.5414/CP203843.
Bepridil prolongs the QT interval and can induce torsade de pointes. Although increased bepridil concentration may be a primary cause of prolonged QT, the relationship between serum bepridil concentration and prolonged QT remains unclear. We investigated the relationship between serum bepridil concentration and the corrected QT (QTc) interval in patients treated with bepridil.
A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. Patients with atrial fibrillation who were treated with bepridil from January 2014 to December 2015 were enrolled in the study. Serum bepridil concentrations and electrocardiogram data collected more than 21 days after the initiation of bepridil were used for analysis.
A total of 60 patients were included in this study. There was a significant difference in mean QTc interval before and after initiation of bepridil (p < 0.0001). A significant relationship was observed between bepridil dose (p = 0.014) or serum bepridil concentration (p < 0.001) and QTc interval. Additionally, a significant relationship was observed between serum bepridil concentration and ΔQTc (p = 0.034). In the study, 4 patients developed QTc prolongation ≥ 500 ms after the initiation of bepridil. Serum bepridil concentration in this group was significantly higher compared with the group that did not display prolonged QTc (973 ± 651 vs. 526 ± 310 ng/mL, p = 0.01).
This study revealed that the QTc interval was significantly associated with serum bepridil concentration. Serum bepridil concentration beyond a therapeutic range may be a critical risk factor for developing QTc prolongation.
比哌立登延长 QT 间期，并可诱发尖端扭转型室性心动过速。虽然比哌立登浓度增加可能是导致 QT 延长的主要原因，但血清比哌立登浓度与 QT 延长之间的关系尚不清楚。我们研究了比哌立登治疗患者的血清比哌立登浓度与校正 QT（QTc）间期之间的关系。
本研究在日本国立循环器病研究中心进行，回顾性分析了 2014 年 1 月至 2015 年 12 月期间接受比哌立登治疗的心房颤动患者。入选标准为：比哌立登起始治疗后 21 天以上收集血清比哌立登浓度和心电图数据。
本研究共纳入 60 例患者。比哌立登起始前后 QTc 间期的平均值有显著差异（p < 0.0001）。比哌立登剂量（p = 0.014）或血清比哌立登浓度（p < 0.001）与 QTc 间期呈显著相关。此外，血清比哌立登浓度与ΔQTc 之间也存在显著关系（p = 0.034）。在研究过程中，有 4 例患者在开始使用比哌立登后出现 QTc 延长≥500ms。与 QTc 无延长的患者相比，该组的血清比哌立登浓度明显升高（973 ± 651 比 526 ± 310ng/ml，p = 0.01）。
本研究表明，QTc 间期与血清比哌立登浓度显著相关。血清比哌立登浓度超过治疗范围可能是导致 QTc 延长的关键危险因素。
