Original
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
Price
42.00 $
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
Original
Discontinuation of oral amphotericin B therapy does not influence the pharmacokinetics of tacrolimus in heart transplant patients
Megumi Ikura, Tsutomu Nakamura, Takaya Uno, Kazuki Nakagita, Hiromi Takenaka, Sachi Matsuda, Ryosuke Oda, Kyoichi Wada, Yuji Hattori, Osamu Seguchi, Masanobu Yanase, Naoki Hayakawa, and Norihide Fukushima
Price
42.00 $
Volume 59 (2021) p. 566 - 571
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 59 – No. 8/2021 (566-571)
Discontinuation of oral amphotericin B therapy does not influence the pharmacokinetics of tacrolimus in heart transplant patients
Megumi Ikura1, Tsutomu Nakamura2, Takaya Uno1, Kazuki Nakagita1, Hiromi Takenaka1, Sachi Matsuda1, Ryosuke Oda1, Kyoichi Wada2, Yuji Hattori1, Osamu Seguchi3, Masanobu Yanase3, Naoki Hayakawa1, and Norihide Fukushima3
1Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, 2Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, and 3Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
Objective: Amphotericin B (AMPH-B) is used to prevent opportunistic infections associated with immunosuppressive therapy after heart transplantation (HTx), while the blood concentrations of tacrolimus (TAC) are carefully controlled. Although AMPH-B has the potential to inhibit TAC metabolism in in vitro studies, its interaction with clinically used AMPH-B oral suspension has not been investigated. In the present study, we examined whether oral AMPH-B therapy influences the pharmacokinetics of TAC in HTx patients.
Materials and methods: A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. All patients with HTx enrolled in the study received standard triple-drug immunosuppression therapy including the regular release of TAC, mycophenolate mofetil, and prednisolone as well as prophylactic therapy with AMPH-B oral suspension. Patient characteristics and clinical laboratory data were collected from the electronic medical record system. Blood concentrations of TAC were used for pharmacokinetic analysis.
Results: A total of 14 patients were enrolled in the study. There were no statistically significant differences in the variables except for serum creatinine levels and eGFR before and after discontinuation of oral AMPH-B therapy. The dose and trough concentrations of TAC and the area under the time-concentration curve and apparent oral clearance calculated from its concentrations were not influenced by discontinuation of AMPH-B treatment.
Conclusion: The prophylactic treatment with AMPH-B oral suspension did not influence the pharmacokinetics of TAC and was demonstrated as a safe and easy method to prevent early post-HTx fungal infection.Correspondence to:
Tsutomu Nakamura, PhD, Professor
Education and Research Center for Clinical Pharmacy
Faculty of Pharmacy, Osaka Medical and Pharmaceutical University
4-20-1 Nasahara, Takatsuki 569-1094, Japan
Email: [email protected]
Original
Early acute kidney injury after tacrolimus administration in heart transplant recipients receiving basiliximab induction therapy
Megumi Ikura, Tsutomu Nakamura, Kyoichi Wada, Rikako Nagata, Tomoko Ueno, Kazuyoshi Kawabata, Fumiki Yoshihara, Takuya Watanabe, and Yasumasa Tsukamoto
Price
42.00 $
Volume 62 (2024) p. 525 - 533
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 62 – No. 11/2024 (525-533)
Early acute kidney injury after tacrolimus administration in heart transplant recipients receiving basiliximab induction therapy
Megumi Ikura1, Tsutomu Nakamura2, Kyoichi Wada2, Rikako Nagata1, Tomoko Ueno1, Kazuyoshi Kawabata1, Fumiki Yoshihara3, Takuya Watanabe4, and Yasumasa Tsukamoto4
1Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, 2Education and Research Center for Clinical Pharmacy, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Takatsuki, 3Department of Hypertension and Nephrology, and 4Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
Objective: In this study, we aimed to analyze the association among the timing of tacrolimus initiation, time required to reach the target blood concentration, and early acute kidney injury (AKI) after tacrolimus administration in heart transplant recipients who received basiliximab induction therapy.
Materials and methods: 88 patients treated with tacrolimus-based immunosuppressive therapy were retrospectively reviewed. Induction therapy was administered to 52 patients. AKI was evaluated within 7 days of tacrolimus administration.
Results: The rate of increase in tacrolimus trough concentration to the target trough concentration of 10 µg/mL early after its administration was set to be similar in the basiliximab induction and non-induction group; 8 and 2 patients developed AKI in the induction and non-induction group, respectively. In the induction group, there was no significant difference in the timing of tacrolimus initiation and the time required to reach the target concentration between patients who developed and did not develop AKI. In contrast, the cumulative incidence of AKI was significantly different between patients with an estimated glomerular filtration rate below and those with an estimated glomerular filtration rate above 43 mL/min/1.73m2 at the start of tacrolimus administration (37.5% and 11.4%, respectively; p = 0.045).
Conclusion: In patients receiving basiliximab induction therapy, the timing of tacrolimus initiation and the time to reach the target concentration are unlikely to be associated with early AKI after tacrolimus administration. However, the recovery of sufficient renal function after heart transplantation is important for determining the start time of tacrolimus.Correspondence to:
Tsutomu Nakamura, PhD, Professor
Education and Research Center for Clinical Pharmacy
Faculty of Pharmacy
Osaka Medical and Pharmaceutical University
4-20-1 Nasahara, Takatsuki 569-1094, Japan
Email: [email protected]
Corrigendum
Corrigendum for the article Int J Clin Pharmacol Ther 2024; 11: 525-533
Megumi Ikura, Tsutomu Nakamura, Kyoichi Wada, Rikako Nagata, Tomoko Ueno, Kazuyoshi Kawabata, Fumiki Yoshihara, Takuya Watanabe, and Yasumasa Tsukamoto
Volume 62 (2024) p. 582 - 582
Abstract
Intern. Journal of Clinical Pharmacology and Therapeutics, Vol. 62 – No. 12/2024 – Corrigendum
Corrigendum for the article Int J Clin Pharmacol Ther 2024; 11: 525-533
Megumi Ikura, Tsutomu Nakamura, Kyoichi Wada, Rikako Nagata, Tomoko Ueno, Kazuyoshi Kawabata, Fumiki Yoshihara, Takuya Watanabe, and Yasumasa Tsukamoto
