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Relationship between serum bepridil concentration and corrected QT interval 

Kazuki Matsui, Yutaro Mukai, Kota Sakakura, Kyoichi Wada, Tsutomu Nakamura, Atsufumi Kawabata, Nobue Terakawa, Naoki Hayakawa, Kengo Kusano, Kouichi Hosomi, Satoshi Yokoyama, and Mitsutaka Takada

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Volume 59 (2021) p. 63 - 70

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 59 – No. 1/2021 (63-70)

Relationship between serum bepridil concentration and corrected QT interval 

Kazuki Matsui¹#²#³, Yutaro Mukai³, Kota Sakakura³, Kyoichi Wada⁴, Tsutomu Nakamura⁴, Atsufumi Kawabata², Nobue Terakawa³, Naoki Hayakawa³, Kengo Kusano⁵, Kouichi Hosomi⁶#⁷, Satoshi Yokoyama⁶#⁷, and Mitsutaka Takada¹#⁶#⁷

¹Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, ²Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, ³Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, ⁴Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, ⁵Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, ⁶Division of Clinical Drug Informatics, Kindai University Graduate School of Pharmacy, and ⁷Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-Osaka, Japan
Objective: 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.
Materials and methods: 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.
Results: 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).
Conclusion: 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.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
Kindai University Graduate School of Pharmacy
Higashi-Osaka, Osaka, 577-8502, Japan
Email:  takada@ phar.kindai.ac.jp

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