Papers - IKEDA Ryuji
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Promotion of Generic Drugs through the Medical SPD System and Efficacy of Drug Cost Reduction Reviewed
Sekiya Hiroshi, Ogata Yutaka, Kajiwara Takahiro, Fukunaga Yoko, Moriki Toyosaka, Ikeda Ryuji
Japanese Journal of Drug Informatics 23 ( 1 ) 38 - 46 2021.5
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Society of Drug Informatics
DOI： 10.11256/jjdi.23.38
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Impact of green tea intake on the pharmacokinetics of celiprolol in healthy subjects Reviewed
Sonoda J., Ogata K., Yoshikawa N., Sato K., Ikeda R., Shimodozono Y.
International Journal of Clinical Pharmacology and Therapeutics 59 ( 3 ) 198 - 201 2021.3
Publishing type：Research paper (scientific journal) Publisher：International Journal of Clinical Pharmacology and Therapeutics
Objective: To assess the effect of green tea intake on the pharmacokinetics of the β-blocker celiprolol. Materials and method: In an open-label crossover study, 3 healthy subjects were given water or a green tea beverage daily for 3 days. On day 4, each subject received a single oral dose of 200 mg celiprolol with water or green tea. Serum and urinary concentrations of celiprolol were measured for up to 24 hours. Results: Green tea intake decreased the area under the serum concentration-time curve and urinary excretion of celiprolol by 98.6 and 98.0%, respectively. Conclusion: Green tea intake might have a negative impact on the clinical effectiveness of celiprolol.
DOI： 10.5414/CP203795
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Yoshikawa N., Yamada A., Yokota T., Moritake H., Hirabara Y., Ikeda R.
Journal of Clinical Laboratory Analysis 35 ( 3 ) e23661 2021.3
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Clinical Laboratory Analysis
Background: The concentration of MTX in blood is often measured quickly and easily by immunoassays. Thus, immunoassays may facilitate the easy determination of the concentration of MTX in the cerebrospinal fluid (CSF). In this study, we measured methotrexate (MTX) concentrations in the CSF using a high-performance liquid chromatography (HPLC) method intended for analyzing CSF matrices and a chemiluminescence immunoassay (CLIA) method intended for assessing serum and plasma matrices and verified the differences in the results of the two methods. Methods: HPLC analysis for MTX in the CSF was performed using a Prominence UFLC system with a C18 column. The HPLC method was validated in accordance with the 2018 FDA guideline. The CLIA method was performed using an ARCHITECT i1000SR system intended for serum and plasma matrices. A total of 47 CSF samples (14 clinical and 33 spiked specimens) were analyzed using the two methods. Results: The HPLC method passed the validation criteria. The concentration of MTX in the same sample, determined using the HPLC and CLIA methods, differed proportionally; the percent difference in the concentrations averaged −23.0% (95% confidence interval: −36.9% to −9.1%) as revealed by the Bland-Altman plot. The relationship between the measured values, evaluated using the Passing-Bablok regression, was as follows: HPLC = 1.205 × CLIA – 0.024. Conclusion: The equation deduced in this study can be used to correct the concentration of MTX measured using the CLIA method.
DOI： 10.1002/jcla.23661
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Tsuruda T., Yoshikawa N., Kai M., Yamaguchi M., Toida R., Kodama T., Kajihara K., Kawabata T., Nakamura T., Sakata K., Hatakeyama K., Gi T., Asada Y., Tono T., Kitamura K., Ikeda R.
Internal Medicine 60 ( 3 ) 423 - 429 2021.2
Language：English Publishing type：Research paper (scientific journal) Publisher：Internal Medicine
We herein report the cytokine expression at different stages for three patients who developed cardiac complications after immune checkpoint inhibitor (ICI) therapy. Case 1 with biopsy-proven myocarditis showed increased levels of interleukin (IL)-8, monocyte chemotactic and activating factor, and granulocyte macrophage colony-stimulating factor (GM-CSF) when he developed Takotsubo cardiomyopathy. Case 2 with subclinical myocarditis showed predominant activation of IL-8 during the progressive clinical course. Case 3 with cytokine-releasing syndrome showed substantial activations of IL-6, IL-8, GM-CSF, and interferon-γ. Our data suggest the development of unique cytokine activation in individual patients with cardiac complications after ICI therapy.
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Yoshikawa N., Takeshima H., Sekine M., Akizuki K., Hidaka T., Shimoda K., Ikeda R.
Pharmaceuticals 14 ( 4 ) 2021
Language：English Publishing type：Research paper (scientific journal) Publisher：Pharmaceuticals
A polymorphism in the gene encoding the metabolic enzyme cytochrome P450 family 3 subfamily A member 5 (CYP3A5) is a particularly influential factor in the use of tacrolimus in Japanese patients. Those who are homozygotic for the *3 mutation lack CYP3A5 activity, which results in substantial individual differences in tacrolimus metabolism. The aim of this study was to analyze the relationship between individual differences in tacrolimus blood concentration changes and CYP3A5 polymorphisms in allogeneic hematopoietic stem cell transplantation recipients during the period of increasing blood concentration of the drug following treatment onset. This was a prospective observational cohort study, involving 20 patients administered tacrolimus by continuous infusion. The subjects were divided into the *1/*3 and *3/*3 groups based on CYP3A5 polymorphism analysis. The tacrolimus blood concentration/dose (C/D) ratio increased from day 1 and was largely stable on day 5, and a significant difference was observed between the *1/*3 and *3/*3 groups in the time course of the C/D ratio during this period (p < 0.05). This study reveals the effects om on continuous changes in tacrolimus blood concentration.
DOI： 10.3390/ph14040353
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Retrospective analysis of risk factors for liposomal amphotericin B-associated nephrotoxicity Reviewed
Yokota T., Yoshikawa N., Arimori K., Ikeda R.
Pharmazie 75 ( 11 ) 599 - 601 2020.11
Language：English Publishing type：Research paper (scientific journal) Publisher：Pharmazie
In this study, we examined patients who received liposomal amphotericin B (L-AMB) to determine the risk factors associated with nephrotoxicity before and during L-AMB treatment. In this retrospective, single-center, observational cohort study, we examined 37 patients who received L-AMB treatment between April 2018 and December 2019. Nephrotoxicity was observed in 11 (29.7%) patients. We focused on the baseline albumin level and body surface area (BSA) before L-AMB treatment. Univariate analysis showed that the BSA and baseline albumin levels in patients with nephrotoxicity were significantly higher than those in patients without nephrotoxicity. Moreover, univariate analysis showed that albumin supplementation was significantly associated with the frequency of nephrotoxicity during L-AMB treatment. Multiple logistic regression analysis revealed the following independent risk factors for nephrotoxicity before or during L-AMB treatment: baseline albumin level (odds ratio [OR] = 16.000; 95% CI 1.480-172.000; P = 0.022) and albumin supplementation (OR = 40.800; 95% CI 2.210-753.000; P = 0.013). In conclusion, we identified baseline albumin level and albumin supplementation as novel risk factors for L-AMB-induced nephrotoxicity.
DOI： 10.1691/ph.2020.0731
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Role of FK506 Binding Protein on Tacrolimus Distribution in Red Blood Cells Reviewed
Yoshikawa N., Yokota T., Matsuo A., Matsumoto N., Iwakiri T., Ikeda R.
Pharmaceutical Research 37 ( 7 ) 143 2020.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Pharmaceutical Research
Purpose: Tacrolimus is distributed mainly in red blood cells (RBCs) after transfer into blood. This study aimed to evaluate the effect of FK506-binding proteins (FKBPs) on RBC distribution of tacrolimus in a physiological environment. Methods: Human RBCs were isolated from fresh blood samples from healthy volunteers. The effect of FKBPs on each process of the RBC distribution of tacrolimus was evaluated in vitro. Effect of intracellular FKBPs was assessed by inhibition experiment with rapamycin, which competitively inhibits the binding of tacrolimus to FKBPs. Effect of extracellular FKBPs was examined by pre-exposure of RBCs to FKBP and preincubation of tacrolimus with FKBP. Results: Pretreatment with rapamycin significantly reduced the rate of tacrolimus distribution in RBCs in a concentration-dependent manner. Pre-exposure of RBCs to FKBP12 followed by exposure to tacrolimus significantly decreased tacrolimus distribution in RBCs in a concentration-dependent manner. In addition, preincubation of tacrolimus with FKBP12 significantly reduced the rate of tacrolimus distribution in RBCs. Conclusions: FKBP played an important role in the distribution of tacrolimus in RBCs. The effect of intracellular and extracellular FKBPs on RBC distribution of tacrolimus in circulating blood was substantial. FKBP was shown as a potential biomarker for predicting the pharmacokinetics and pharmacodynamics of tacrolimus.
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Retrospective analysis of the correlation between tacrolimus concentrations measured in whole blood and variations of blood cell counts in patients undergoing allogeneic haematopoietic stem cell transplantation. Reviewed
Yoshikawa N, Urata S, Yasuda K, Sekiya H, Hirabara Y, Okumura M, Ikeda R.
Eur J Hosp Pharm 2020.3
Language：English Publishing type：Research paper (scientific journal)
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Retrospective analysis of the correlation between tacrolimus concentrations measured in whole blood and variations of blood cell counts in patients undergoing allogeneic haematopoietic stem cell transplantation. Reviewed
Yoshikawa N, Urata S, Yasuda K, Sekiya H, Hirabara Y, Okumura M, Ikeda R
European journal of hospital pharmacy : science and practice 27 ( e1 ) e7 - e11 2020.3
Language：English Publishing type：Research paper (scientific journal)
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バイオシミラー導入への取り組みと薬剤費削減効果 Reviewed
池田 龍二
ジェネリック研究 14 25 - 33 2020
Publishing type：Research paper (scientific journal)
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Anti-proliferative Activities of Some Bivalent Symmetrical 5-Substituted Hydantoin Derivatives towards Human Brain Glioma U251 Cells (U251) and Human Carcinoma Cells (KB3-1). Reviewed
Furutachi M, Ota K, Fujisaki F, Ikeda R, Yoshikawa N, Yokota T, Takeda Y, Yokomizo K, Zhou JR, Kashige N, Miake F, Sumoto K.
Biol Pharm Bull. 2019.11
Language：English Publishing type：Research paper (scientific journal)
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医薬品SPDを活用したタスク・シフティングの検討 Reviewed
関屋裕史、友宗直樹、緒方豊、梶原隆広、福永洋子、森木豊栄、長友隆雄、岩田円夏、萩原櫻子、池田 龍二
九州薬学会雑誌 2019.11
Language：Japanese Publishing type：Research paper (scientific journal)
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当院の持参薬鑑別時におけるお薬手帳の利用状況とお薬手帳の記載内容調査 Reviewed
外山智章、畑中真理、田﨑智也、竹島秀美、平原康寿、池田 龍二
九州薬学会雑誌 2019.11
Language：Japanese Publishing type：Research paper (scientific journal)
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電子カルテシステムのベンダー変更を契機としたがん薬物療法レジメンの見直しと医療安全に向けた取り組み Reviewed
浦田修平、大野梨絵、千阪智美、北畑恵理子、髙橋沙季、是枝秀彦、森山徳文、平原康寿、池田 龍二
九州薬学会雑誌 2019.11
Language：Japanese Publishing type：Research paper (scientific journal)
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宮崎県病院施設における薬薬連携の現状調査 Reviewed
田﨑智也、平原康寿、本田憲一、三代朗子、杉田昌子、永友由里子、高橋雅也、津曲恭一、帖佐康弘、寺町文宏、長友隆雄、外山智章、山口博行、奥村学、佐藤智加子、池田 龍二
九州薬学会雑誌 2019.11
Language：Japanese Publishing type：Research paper (scientific journal)
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5-Aza-2-deoxycytidine Enhances the Sensitivity of 5-Fluorouracil by Demethylation of the Thymidine Phosphorylase Promoter. Reviewed
Nishizawa Y, Ikeda R, Yamamoto M, Kawahara K, Shinsato Y, Minami K, Nitta M, Terazono H, Akiyama SI, Furukawa T, Takeda Y.
Anticancer Res 2019.8
Language：English Publishing type：Research paper (scientific journal)
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Anti-proliferative Activities towards Human Brain Glioma U251 Cells and Human Carcinoma Cells (KB3-1) of Some Twin-Drug Type Bivalent C2-Symmetrical Phenylboronic Acid Derivatives. Reviewed
Furutachi M, Gondo T, Ikeda R, Yoshikawa N, Yokota T, Takeda Y, Yokomizo K, Zhou JR, Kashige N, Miake F, Sumoto K.
Biol Pharm Bull 2019.5
Language：English Publishing type：Research paper (scientific journal)
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Drug-drug interactions among drugs prescribed for nontuberculous mycobacterial infection and epilepsy: A case report. Reviewed
Yoshikawa N, Tazaki T, Hatanaka M, Oda Y, Matsumoto N, Sonoda J, Ikeda R.
Journal of Clinical Pharmacy and Therapeutics 2019.2
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Viva-Eシステムとナノピア®TDMエベロリムス試薬によるエベロリムス血中濃度測定の基礎的評価 Reviewed
吉川 直樹、横田 翼、関屋 裕史、平原 康寿、池田 龍二
日本病院薬剤師会雑誌 2019.1
Language：Japanese Publishing type：Research paper (scientific journal)
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Tabata S., Yamamoto M., Goto H., Hirayama A., Ohishi M., Kuramoto T., Mitsuhashi A., Ikeda R., Haraguchi M., Kawahara K., Shinsato Y., Minami K., Saijo A., Toyoda Y., Hanibuchi M., Nishioka Y., Sone S., Esumi H., Tomita M., Soga T., Furukawa T., Akiyama S.
Scientific Reports 8 ( 1 ) 2018.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports
© 2018 The Author(s). Thymidine phosphorylase (TP) is a rate-limiting enzyme in the thymidine catabolic pathway. TP is identical to platelet-derived endothelial cell growth factor and contributes to tumour angiogenesis. TP induces the generation of reactive oxygen species (ROS) and enhances the expression of oxidative stress-responsive genes, such as interleukin (IL)-8. However, the mechanism underlying ROS induction by TP remains unclear. In the present study, we demonstrated that TP promotes NADPH oxidase-derived ROS signalling in cancer cells. NADPH oxidase inhibition using apocynin or small interfering RNAs (siRNAs) abrogated the induction of IL-8 and ROS in TP-expressing cancer cells. Meanwhile, thymidine catabolism induced by TP increased the levels of NADPH and intermediates of the pentose phosphate pathway (PPP). Both siRNA knockdown of glucose 6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme in PPP, and a G6PD inhibitor, dihydroepiandrosterone, reduced TP-induced ROS production. siRNA downregulation of 2-deoxy-D-ribose 5-phosphate (DR5P) aldolase, which is needed for DR5P to enter glycolysis, also suppressed the induction of NADPH and IL-8 in TP-expressing cells. These results suggested that TP-mediated thymidine catabolism increases the intracellular NADPH level via the PPP, which enhances the production of ROS by NADPH oxidase and activates its downstream signalling.