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Faculty of Medicine College Hospital Medicine |
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IKEDA Ryuji
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Papers 【 display / non-display 】
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Yoshikawa N., Ehara Y., Yamada Y., Matsusaki Y., Shimoda K., Ikeda R.
Scientific Reports 15 ( 1 ) 3364 2025.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports
Intra-patient variability in immunosuppressive blood drug concentrations is a potential biomarker in managing organ transplant patients. However, the association between the time in therapeutic range of tacrolimus blood concentrations and its efficacy in preventing graft-versus-host disease remains unknown. In this study, we analyzed the relationship between the time in therapeutic range of tacrolimus blood concentrations and its efficacy in acute graft-versus-host disease prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation. Eligible patients administered tacrolimus were categorized into two groups based on the grade of acute graft-versus-host disease, and propensity score matching was performed using graft-versus-host disease prophylaxis protocols and days to the disease onset to compare time in therapeutic range. In patients with tacrolimus blood concentration therapeutic range ≥ 10 ng/mL, time in therapeutic range during the first 4 weeks post-transplantation was significantly lower in the Grade II–III than in the Grade 0–I group. Among propensity score matching-extracted patients, the Grade II–III group had significantly lower time in therapeutic range during the first 2 and 4 weeks post-transplantation. Our results suggest that high time in therapeutic range early post-transplantation, particularly within 4 weeks, may avert the severity of acute graft-versus-host disease.
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Yasuda K., Hirano Y., Takeda R., Ikeda R., Ishida Y.
Neuropsychopharmacology Reports 45 ( 1 ) e12506 2025.3
Language：English Publishing type：Research paper (scientific journal) Publisher：Neuropsychopharmacology Reports
Aim: Suvorexant is an orexin receptor antagonist (ORA) for the treatment of insomnia. The antagonistic action of suvorexant on orexin receptors is associated with an increase in rapid eye movement (REM) sleep, which can potentially lead to nightmares depending on the patient's condition. However, the precise risk factors for nightmares among patients taking ORAs, such as suvorexant, have yet to be identified. In this retrospective study, we aimed to identify the risk factors for the development of nightmares in patients treated with suvorexant. Methods: The risk factors were determined by comparing parameters between the nightmare group and the nonnightmare group. This study included 440 patients who received suvorexant at the University of Miyazaki Hospital from April 2014 to January 2021. Results: We found that 9.1% (n = 40) of the patients experienced suvorexant-induced nightmares. There was a significant difference in the median age, which was lower in the nightmare group than in the nonnightmare group (p < 0.01). Furthermore, both multiple logistic regression analysis and Cox proportional hazards regression analysis revealed increased odds ratios for nightmares for individuals aged 20–39 years. Conclusions: This study revealed that elderly patients taking suvorexant had fewer nightmares than nonelderly patients did.
DOI： 10.1002/npr2.12506
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Yamada Y., Ishitsuka Y., Fukaura-Nishizawa M., Kawata T., Ishii A., Shirakawa A., Sakai T., Tanaka M., Kondo Y., Takeo T., Nakagata N., Motoyama K., Higashi T., Arima H., Seki T., Kurauchi Y., Katsuki H., Higaki K., Ikeda R., Matsuo M., Era T., Irie T.
Life Sciences 350 122776 2024.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Life Sciences
Niemann–Pick disease type C (NPC) is a lysosomal lipid storage disorder characterized by progressive neurodegeneration and hepatic dysfunction. A cyclic heptasaccharide, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), is currently under clinical investigation for NPC, but its adverse events remain problematic. We previously identified that a cyclic octasaccharide, 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD), also ameliorated NPC manifestations with higher biocompatibility than HP-β-CD. However, preclinical studies describing the associations between the biodistribution and pharmacodynamics of these compounds, which are essential for clinical application, are still lacking. Here, we investigated these properties of HP-γ-CD by measuring its organ biodistribution and therapeutic effect after systemic and central administration. The effect of HP-γ-CD on disturbed cholesterol homeostasis appeared within several hours after exposure and persisted for several days in NPC model cells and mice. Tissue distribution indicated that only a small fraction of subcutaneously administered HP-γ-CD rapidly distributed to peripheral organs and contributed to disease amelioration. We found that a subcutaneous dose of HP-γ-CD negligibly ameliorated neurological characteristics because it has limited penetration of the blood–brain barrier; however, an intracerebroventricular microdose unexpectedly attenuated hepatic dysfunction without the detection of HP-γ-CD in the liver. These results demonstrate that central administration of HP-γ-CD can indirectly attenuate peripheral manifestations of NPC.
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Yoshikawa N., Nagatomo T., Matsusaki Y., Yokota T., Yamada Y., Ikeda R.
Pharmazie 79 ( 6 ) 114 - 117 2024.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Pharmazie
The therapeutic effect of tacrolimus against ulcerative colitis (UC) is correlated with its trough blood concentration. Conventionally, oral tacrolimus for the treatment of UC is initiated under fasting conditions; once the symptoms improve, food intake is resumed. Tacrolimus blood concentration decreases with food intake compared with that under fasting conditions. The aim of this study was to explore the characteristics of patients with UC whose tacrolimus blood concentrations tended to decrease after food initiation. Medical data of 13 patients with UC and treated with tacrolimus were retrospectively obtained. The participant characteristics associated with the changes in tacrolimus blood concentrations after food initiation were analyzed using regression analysis based on the rate of decrease in the concentration/dose (C/D) ratio after food initiation. Single regression analysis showed that the number of days required from tacrolimus initiation to food resumption (P = 0.0071) and individual differences in the increase in tacrolimus blood concentration after administration (P = 0.0247) were significantly associated with the rate of decrease in the C/D ratio after food initiation. Furthermore, multiple regression analysis showed a significant effect of the number of days to food resumption (P = 0.0004) and individual differences in the increase in tacrolimus blood concentration after administration (P = 0.0012). The results suggest that the degree of change in blood tacrolimus concentration after food initiation may be related to the severity of the symptoms and pathology of UC. Early identification of participant characteristics may help control tacrolimus blood concentration fluctuations after food initiation.
DOI： 10.1691/ph.2024.4501
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Ishii Saya, Ozaki Mineo, Takamura Norito, Ogata Kenji, Tokunaga Jin, Ikeda Ryuji
Biological and Pharmaceutical Bulletin 47 ( 1 ) 213 - 220 2024.1
Language：English Publishing type：Research paper (scientific journal) Publisher：The Pharmaceutical Society of Japan
Diclofenac instillation is useful in preventing intraoperative miosis and macular edema caused by postoperative inflammation in cataract surgery; however, optimum efficacy is not attained when the instilled diclofenac strongly binds to albumin in patients’ aqueous humor. Therefore, a method that inhibits diclofenac binding and increases the concentration of its free fraction is needed. We conducted a basic study regarding the effects of inhibitors on the binding of instilled diclofenac to albumin and endogenous substances in aqueous humor. Aqueous humor samples from 16 patients were pooled together for analysis. The free fraction of diclofenac was measured using ultrafiltration methods in various experiments with pooled and mimic aqueous humor. Free fraction of diclofenac, a site II drug, in pooled aqueous humor was 0.363 ± 0.013. The binding of diclofenac in the presence of phenylbutazone (PB), a site I inhibitor, was significantly inhibited (free fraction = 0.496 ± 0.013); however, no significant inhibition by ibuprofen, a site II inhibitor, (free fraction = 0.379 ± 0.004), was observed. The unexpected result was due to free fatty acids (FFAs; palmitic acid (PA)) and L-tryptophan (Trp). The inhibition of diclofenac binding by PB in the mimic aqueous humor containing these endogenous substances revealed significant binding inhibition in the presence of PA and Trp. Diclofenac is strongly rebound from site II to site I in the presence of FFAs and Trp in the aqueous humor because FFAs and Trp induce a conformational change in albumin. Therefore, PB significantly inhibits the binding of diclofenac to albumin.
Books 【 display / non-display 】
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武田 泰生, 齋藤 秀之 (応用薬理学), 伊東 弘樹, 池田 龍二 (医療系薬学), 柳田 俊彦（ Role： Sole author）
南山堂 2023 （ ISBN:9784525500719 ）
Language：Japanese Book type：Scholarly book
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臨床薬学テキストシリーズ 循環器／腎・泌尿器／代謝／内分泌：「第3章代謝性疾患-B疾患各論-③脂質異常症」
武田泰生、池田龍二、石橋俊（ Role： Joint author）
中山書店 2020.1
Language：Japanese Book type：Textbook, survey, introduction
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The dynamics of social capital and civic engagement in Asia
Daniere Amrita, Luong Hy V.
Routledge 2012
Language：Japanese
MISC 【 display / non-display 】
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Owatari S., Akune S., Komatsu M., Ikeda R., Firth S., Che X., Yamamoto M., Tsujikawa K., Kitazono M., Ishizawa T., Takeuchi T., Aikou T., Mercer J., Akiyama S., Furukawa T.
Cancer Research 67 ( 13 ) 2007.7
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution) Publisher：Cancer Research
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Inoue I., Ikeda R., Tsukahara S.
Journal of Pharmacological Sciences 100 ( 3 ) 205 - 210 2006.3
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution) Publisher：Journal of Pharmacological Sciences
To understand the molecular pathogenesis of ossification of the posterior longitudinal ligament of the spine (OPLL), an ectopic bone formation disease, we performed cDNA microarray analysis on cultured ligament cells from OPLL patients to understand the molecular pathogenesis of OPLL. We identified promyelotic leukemia zinc finger (PLZF) as one of up-regulated genes and tumor necrosis factor-α-stimulated gene 6 (TSG-6) as one of down-regulated gene during osteoblastic differentiation. We investigated the roles of PLZF in the regulation of osteoblastic differentiation of human mesenchymal stem cells (hMSCs) and C2C12 cells. siRNA-mediated gene-silencing of PLZF resulted in a reduction of the expression of osteoblast-specific genes such as the alkaline phosphatase, collagen 1A1, Runx2/CBFA1, and osteocalcin genes in the presence of osteogenic differentiation medium (OS) in hMSCs. The overexpression of PLZF induced CBFA1 induction, suggesting that PLZF is an upstream regulator of CBFA1 and thereby participates in promoting the ossification of spinal ligament cells in OPLL patients. Adenoirus-mediated TSG-6 overexpression in hMSCs resulted in suppression of oseoblastic differentiation induced by either BMP-2 or OS. TSG-6 can bind to BMP-2 directly and thereby could inhibit BMP-2 signaling. Taken together, these findings indicate that PLZF and TSG-6 play important roles in early osteoblastic differentiation. ©2006 The Japanese Pharmacological Society.
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Okumura H., Chen Z., Sakou M., Sumizawa T., Furukawa T., Komatsu M., Ikeda R., Suzuki H., Hirota K., Aikou T., Akiyama S.
Molecular Pharmacology 58 ( 6 ) 1563 - 1569 2000
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution) Publisher：Molecular Pharmacology
A newly synthesized taxoid originally from the Japanese yew Taxus cuspidata, 5-O-benzoylated taxinine K (BTK) was examined for its ability to reverse P-glycoprotein (P-gp) and multidrug resistance protein (MRP)-mediated multidrug resistance. BTK reversed the resistance to paclitaxel, doxorubicin (ADM), and vincristine (VCR) of KB-8-5 and KB-C2 cells that overexpress P-gp by directly interacting with P-gp. BTK also moderately reversed the resistance to ADM of KB/MRP cells that overexpress MRP. However, BTK neither inhibited the transporting activity of MRP nor reduced intracellular glutathione levels in KB/MRP cells. BTK shifted the distribution of ADM in KB/MRP cells from punctate cytoplasmic compartments to the nucleoplasm and cytoplasm by inhibiting acidification of cytoplasmic organelles. These two functions of BTK make it able to reverse both P-gp- and MRP-mediated MDR. BTK in combination with ADM should be useful for treating patients with tumors that overexpress both P-gp and MRP.
Presentations 【 display / non-display 】
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MAC 治療薬の併用開始が抗てんかん薬の薬物体内動態に影響を及ぼした1症例：フェニトイン血中濃度の変動
吉川直樹、田﨑智也、園田純一郎、畑中真理、小田康晴、松元信弘、池田龍二
第40回日本臨床薬理学会学術総会
Event date： 2019.12.4 - 2019.12.6
Language：Japanese Presentation type：Poster presentation
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5-Aza-2-deoxycytidine enhances the sensitivity of 5-fluorouracil by demethylation of SP-1 binding site on Thymidine phosphorylase promoter
Yukihiko Nishizawa，Ryuji Ikeda，Masatatsu Yamamoto，Kohichi Kawahara，Yoshinari Shinsato，Kentaro Minami，Mina Nitta，Hideyuki Terazono，Shin-ichi Akiyama，Tatsuhiko Furukawa，Yasuo Takeda
第29回日本医療薬学会年会
Event date： 2019.11.2 - 2019.11.4
Language：English Presentation type：Poster presentation
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後発医薬品導入におけるカットオフ値の重要性と医療経済効果
関屋裕史、緒方豊、梶原隆広、福永洋子、森木豊栄、池田龍二
第29回日本医療薬学会年会
Event date： 2019.11.2 - 2019.11.4
Language：Japanese Presentation type：Oral presentation (general)
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A retrospective study of urine dipstick analysis and urine protein/creatinine ratio for monitoring proteinuria during anti-VEGF therapy
Shuhei Urata，Nobuhiro Shibata，Rie Ohno，Yasutoshi Hirabara，Ryuji Ikeda： A retrospective study of urine dipstick analysis and urine protein/creatinine ratio for monitoring proteinuria during anti-VEGF therapy
第29回日本医療薬学会年会
Event date： 2019.11.2 - 2019.11.4
Language：English Presentation type：Poster presentation
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AMR 対策アクションプランに向けた抗菌薬適正使用推進と今後の対策
外山智章、平原康寿、岩尾千紘、中山雄貴、荒武舞、山田明輝、高城一郎、岡山昭彦、池田龍二
第29回日本医療薬学会年会
Event date： 2019.11.2 - 2019.11.4
Language：Japanese Presentation type：Poster presentation
Grant-in-Aid for Scientific Research 【 display / non-display 】
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実践的看護臨床薬理学教育モデル(iDrug)に基づいた新たな教育システムの開発
Grant number：23K21531 2024.04 - 2025.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(B)
Authorship：Coinvestigator(s)
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がん組織における心筋特異的トロポニンT発現の病態生理学的意義
Grant number：22K08128 2022.04 - 2025.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
鶴田 敏博、
Authorship：Coinvestigator(s)
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実践的看護臨床薬理学教育モデル（iDrug）に基づいた新たな教育システムの開発
Grant number：21H03223 2021.04 - 2025.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(B)
柳田 俊彦、
Authorship：Coinvestigator(s)
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オートファジー細胞死を標的とする新規肺腺癌治療薬の開発
Grant number：21K06691 2021.04 - 2024.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
南 謙太朗、
Authorship：Coinvestigator(s)