Dustri Online Services

Search Results

Books: 0	Journals: 1	Articles: 2

Original

Circadian pharmacokinetics and limited sampling strategy of everolimus in heart transplant patients 

Yuka Terada, Kyoichi Wada, Sachi Matsuda, Takeshi Kuwahara, Atsufumi Kawabata, Mitsutaka Takada, Takuya Watanabe, Seiko Nakajima, Takuma Sato, Osamu Seguchi, Masanobu Yanase, Norihide Fukushima, Takeshi Nakatani

Price
42.00 $

Add to Cart

Price

42.00 $

Volume 55 (2017) p. 1 - 8

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 1/2017 (1-8)

Circadian pharmacokinetics and limited sampling strategy of everolimus in heart transplant patients 

Yuka Terada¹#²#³, Kyoichi Wada¹#³, Sachi Matsuda¹, Takeshi Kuwahara¹#³, Atsufumi Kawabata², Mitsutaka Takada³, Takuya Watanabe⁴, Seiko Nakajima⁴, Takuma Sato⁴, Osamu Seguchi⁴, Masanobu Yanase⁴, Norihide Fukushima⁴, Takeshi Nakatani⁴ 

¹Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, ²Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, ³Division of Cardiovascular Drugs and Therapy, Kindai University Graduate School of Pharmacy, Higashi-Osaka, and ⁴Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Objective: To evaluate circadian changes in everolimus (EVL) pharmacokinetics and to identify the time point of blood sampling with the strongest correlation with the area under the blood concentration-time curve (AUC) of EVL in heart transplant patients. Methods: Heart transplant patients receiving the same dose of EVL twice a day were reviewed. In 28 patients enrolled, whole blood samples were collected before (C₀), and 1, 2, 4, 6, 8, and 12 hours after each administration of EVL. Blood concentrations of EVL were compared between active (9:00 AM to 9:00 PM) and resting periods (9:00 PM to 9:00 AM). Results: AUC_0–4h, peak concentration (C_max), C_max/minimum concentration, and peak-trough fluctuation in the resting period were significantly lower than those in the active period (p = 0.008, 0.017, 0.022, and 0.011, respectively). Half-life and mean residence time were significantly longer in the resting period than in the active period (p = 0.002 and 0.002, respectively). AUC_0–12h in the active period was similar (p = 0.154) and correlated with that in the resting period (r² = 0.93). Two-point blood samplings, C₀ and C₂, correlated more strongly with AUC_0–12h for EVL, compared with C₀ alone (0.92 vs. 0.79, respectively, for r² in the active period). Conclusions: EVL pharmacokinetics showed circadian changes, suggesting delayed absorption and decreased metabolic activity at rest. However, the circadian changes did not affect AUC_0–12h. A 2-time-point model that included C₀ and C₂ was more accurate for predicting the AUC_0–12h of EVL than C₀ alone in heart transplant patients. Correspondence to:
Kyoichi Wada, PhD 
Department of  Pharmacy
National Cerebral and Cardiovascular Center
5-7-1 Fujishirodai, Suita 565-8565, Japan 
Email: [email protected]

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 $

Add to Cart

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

Shopping Overview

Shopping Overview
Type	Qtty	Discount	VAT	Price
Your basket is empty

View Cart

Search Results

Shopping Overview

Send us an E-Mail