Nov. 2024

Nov. 2018

Feb. 2018

2015
Highlighted Article
Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology

Assessment of Pitfalls in an AI-Based Pill-Counting Application
Namie Tanamachi; Takahiro Amemiya; Takashi Tomita
Cureus, 23 Aug. 2025, [Reviewed]

Pitfalls of a Drug-Dispensing Audit Support System
01 Aug. 2025, [Reviewed]

Risk Factors for Infusion Reactions Associated With Rituximab Therapy　　　　　　　　　　　　　　　
TAKAHIRO AMEMIYA; HIROSHI SUZUKI
CANCER DIAGNOSIS & PROGNOSIS, Jul. 2025, [Reviewed]

Verifying the Usefulness of Anticancer Drug-Degrading Agents Using the Residual Amount of Fluorouracil After Wiping as an Indicator
Kanako Shimizu; Takahiro Amemiya; Syunsuke Kumazawa; Tomoharu Takeda; Takashi Tomita; Masanari Takahashi
Cureus, 07 Jan. 2025, [Reviewed]

Retrospective evaluation of medical information for predicting tazobactam/piperacillin-induced liver injury.
Takahiro Amemiya; Hiroshi Suzuki
International journal of clinical pharmacology and therapeutics, Dec. 2024, [Reviewed]
OBJECTIVE: Tazobactam/piperacillin is a first-line treatment option for hospital-acquired pneumonia; however, drug-induced liver injury (DILI) is relatively frequently observed with tazobactam/piperacillin in clinical practice. This study aimed to verify the usefulness of available patient data for predicting DILI prior to tazobactam/piperacillin administration. MATERIALS AND METHODS: Tazobactam/piperacillin-treated patients were retrospectively selected and divided into patients with and without DILI. Comparative analysis was performed regarding age, gender, dose, duration of treatment, clinical laboratory values prior to treatment initiation, and the types of organ-specific infections in both groups. RESULTS: Multiple logistic regression analyses indicated that elevated C-reactive protein (odds ratio (OR), 1.284; 95% confidence interval (CI), 1.172 - 1.406; p < 0.001) and high hemoglobin (OR, 1.697; 95% CI, 1.259 - 2.286; p < 0.001) levels prior to the administration of tazobactam/piperacillin were risk factors for DILI in males who received a 4.5-g dose. A predictive model for DILI risk was constructed by combining these test values and analyzed using receiver operating characteristic curves, obtaining 0.910 for the model construction set and 0.845 for the validation set. CONCLUSION: The development of DILI was predicted with good accuracy in males who received a 4.5-g dose with elevated C-reactive protein and hemoglobin.

Quality Assessment of Functional Claims of Salacia-Derived Salacinol-Containing Foods
Kazumi Kuribayashi; Takahiro Amemiya; Toshikazu Seino; Takashi Tomita
Cureus, 16 Nov. 2024, [Reviewed]

Risk factors for infliximab-induced infusion reactions based on a retrospective study of medical information.
Takahiro Amemiya; Hiroshi Suzuki
International journal of clinical pharmacology and therapeutics, Jul. 2024, [Reviewed]
OBJECTIVE: Infliximab is indicated for a wide range of diseases, and infusion reactions (IRs) have been reported after infliximab administration in 17.6% of patients in clinical practice. This study aimed to identify the risk factors for IRs before the administration of infliximab based on available patient information. MATERIALS AND METHODS: We retrospectively analyzed patients treated with infliximab. Data were compared between patients with and without IRs immediately before initiation of infliximab. RESULTS: Elevated C-reactive protein (CRP) (odds ratio (OR), 2.150; 95% confidence interval (CI), 1.329 - 3.477; p = 0.002) before infliximab administration was a significant risk factor for developing an IR. CONCLUSION: Patients with elevated CRP levels before therapy initiation may require more careful monitoring after infliximab administration.

Non-destructive visualization of internal structural changes in humidified magnesium oxide tablets using X-ray computed tomography.
Takahiro Amemiya; Kazuhiro Suzuki; Takashi Tomita
Scientific reports, 15 Mar. 2024, [Reviewed]
Detailed examinations of the internal structure of tablets are imperative for comprehending their formulation, physical attributes, and ensuring their safe utilization. While X-ray computed tomography (CT) is valuable for noninvasively analyzing internal structural changes, the influence of humidity on these structural changes remains unexplored. Accordingly, we aimed to assess the viability of X-ray CT in non-destructively evaluating the internal structure of humidified magnesium oxide (MgO) tablets. MgO tablets were subjected to conditions of 40 °C and 75% humidity for 7 days, weighed pre- and post-humidification, and subsequently stored at room temperature (22-27 °C) until day 90. Their internal structure was evaluated using X-ray CT. We observed a substantial increase in the weight of MgO tablets concomitant with moisture absorption, with minimal changes observed upon storage at room temperature. The skewness reduced immediately post-moisture absorption, remained almost the same post-storage at room temperature, and failed to revert to pre-humidification levels during the storage period. These findings highlight the utility of X-ray CT as an effective tool for non-destructive, three-dimensional, and detailed evaluation of internal structural transformations in MgO tablets.

Retrospective analysis of risk factors for levofloxacin-induced liver injury.
Takahiro Amemiya; Hiroshi Suzuki
Journal of chemotherapy (Florence, Italy), Dec. 2023, [Reviewed]
Levofloxacin is used as a first-line drug for the treatment of Legionella pneumonia. However, the relatively high incidence of drug-induced liver injury (DILI) remains a clinical problem. Based on the available patient data, this study aimed to identify the risk factors for DILI before levofloxacin administration. Multiple logistic regression analyses suggested that male sex (odds ratio [OR], 6.975; 95% confidence interval [CI], 1.737-28.000; p = 0.006), elevated C-reactive protein level (OR, 1.182; 95% CI, 1.089-1.283; p = 0.0006), and high haemoglobin level (OR, 1.640; 95% CI, 1.226-2.195; p = 0.001) before administration of levofloxacin were risk factors for DILI. Possible treatment with alternative drugs should be considered in male patients with elevated C-reactive protein and haemoglobin levels. Moreover, close monitoring of liver function tests when levofloxacin is administered may prevent the development and severity of DILI.

Risk factors for amiodarone-induced liver injury: A retrospective analysis of medical records.
Hinoo Nagai; Takahiro Amemiya; Hiroshi Suzuki
International journal of clinical pharmacology and therapeutics, Oct. 2023, [Reviewed]
OBJECTIVE: This study identified risk factors for drug-induced liver injury (DILI) based on patient information before the administration of amiodarone. MATERIALS AND METHODS: A retrospective analysis was performed on patients who had received amiodarone treatment. Data from patients with and without DILI were compared immediately before the start of amiodarone treatment. RESULTS: An elevated C-reactive protein level (odds ratio (OR) 1.119; 95% confidence interval (CI) 1.009 - 1.241; p = 0.033) before amiodarone administration was a significant risk factor for DILI. CONCLUSION: Possible treatment with alternative drugs should be considered in patients with elevated C-reactive protein levels. Moreover, close monitoring of liver function when amiodarone is administered may prevent the onset and exacerbation of DILI.

介護老人保健施設において薬剤師が医師回診に同行する有用性の検討　　　　　　　　　　　　　　　
Sep. 2023, [Reviewed]

新生児・乳児に対するカルシウム・リン製剤の同時投与時における吸収量低下リスクの検討
Aug. 2023, [Reviewed]

集中治療室における医薬品情報提供内容に基づくリスクマネジメントへの取り組み　　　　　　　　　　　　　　　
Aug. 2022, [Reviewed]

Retrospective Analysis of Risk Factors for Drug-induced Liver Injury after Cefepime Treatment
AMEMIYA Takahiro; SUZUKI Hiroshi
Therapeutic Research, 2022, [Reviewed]

Exploring Risk Factors for Drug-induced Liver Injury Caused by Meropenem A Case-control Study
雨宮貴洋; 鈴木洋史
Therapeutic Research, 2022, [Reviewed]

Research on the risk factors for the development of paradoxical reactions with midazolam in newborns and infants: a case-control study
櫻井愛; 雨宮貴洋; 鈴木洋史
日本小児臨床薬理学会雑誌, 2022, [Reviewed]

Research on the risk factors for drug-induced liver injury induced by tazobactam/piperacillin in acute care units
雨宮貴洋; 鈴木洋史
Japanese Journal of Antibiotics (Web), 2022, [Reviewed]

Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology.
Takahiro Amemiya; Masashi Honma; Yoshiaki Kariya; Samik Ghosh; Hiroaki Kitano; Yoshihisa Kurachi; Ken-Ichi Fujita; Yasutsuna Sasaki; Yukio Homma; Darrel R Abernethy; Haruki Kume; Hiroshi Suzuki
NPJ systems biology and applications, 2015, [Reviewed]
BACKGROUND/OBJECTIVES: Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach. METHODS: First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments were performed for detailed confirmation of the hypothesized molecular mechanisms and to evaluate the efficacy of a proposed countermeasure against adverse reactions to sunitinib. RESULTS: In silico simulations indicated the possibility that sunitinib-mediated off-target inhibition of phosphorylase kinase leads to the generation of oxidative stress in various tissues. Clinical observations of patients and mouse experiments confirmed the validity of this prediction. The simulation further suggested that concomitant use of an antioxidant may prevent sunitinib-mediated adverse reactions, which was confirmed in mouse experiments. CONCLUSIONS: A systems toxicological approach successfully predicted the molecular mechanisms underlying clinically adverse reactions associated with sunitinib and was used to plan a rational method for the management of these adverse reactions.

Role of protein kinase C beta in phorbol ester-induced c-fos gene expression in neurons of normotensive and spontaneously hypertensive rat brains.
Takahiro Amemiya; Toshie Kambe; Ryuji Fukumori; Takao Kubo
Brain research, 08 Apr. 2005, [Reviewed]
We have previously demonstrated that pressure application of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) onto some neurons in the anterior hypothalamic area of rats increases neural activity in vivo and that this PKC activation-induced increase of neural activity is enhanced in spontaneously hypertensive rats (SHR), an animal model for genetic hypertension. Activation of PKC increases expression of the c-fos gene, an important transcription factor and proto-oncogene thought to be a marker of neural activity. To evaluate PKC isoforms responsible for neural activation, we examined which isoforms of PKC are involved in the PKC activation-induced c-fos gene expression in neuronal cultures of Wistar rat and spontaneously hypertensive rat (SHR) brains. PMA increased c-fos gene expression in neuronal cultures of Wistar rat brain and the PMA-induced c-fos gene expression was inhibited by the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7). The PKCalpha,beta,gamma activator thymeleatoxin also increased c-fos gene expression, while the PKCdelta,epsilon activator ingenol did not affect it. In addition, the PMA-induced c-fos gene expression was inhibited by PKCbetaantisense oligonucleotides (AON) but not by PKCalpha and PKCgammaAONs. In SHR brain neuronal cultures, the PMA-induced c-fos gene expression was enhanced as compared with that of Wistar Kyoto rats (WKY), while basal c-fos gene expression was almost the same in both neuronal cultures. The enhancement of PMA-induced c-fos gene expression in SHR brain cultures was abolished by PKCbetaAON. These findings suggest that in rat brain neuronal cultures, PMA increases c-fos gene expression via activation of PKC and that PKCbetaisoforms are partly involved in the PMA-induced c-fos gene expression. In neuronal cultures of SHR brain, it appears that the PMA-induced c-fos gene expression is also enhanced via PKCbeta.

ドラッグコンサルテーション アピキサバン　　　　　　　　　　　　　　　
Dec. 2019

ドラッグコンサルテーション イルベサルタン　　　　　　　　　　　　　　　
Oct. 2019

ドラッグコンサルテーション GLP-1受容体作動薬　　　　　　　　　　　　　　　
Aug. 2019

ドラッグコンサルテーション エソメプラゾール　　　　　　　　　　　　　　　
Jun. 2019

ドラッグコンサルテーション アメナメビル　　　　　　　　　　　　　　　
Apr. 2019

ドラッグコンサルテーション ミケルナ®配合点眼液　　　　　　　　　　　　　　　
Dec. 2018

ドラッグコンサルテーション デノスマブ　　　　　　　　　　　　　　　
Oct. 2018

ドラッグコンサルテーション シクロスポリン　　　　　　　　　　　　　　　
Aug. 2018

ドラッグコンサルテーション デュタステリド　　　　　　　　　　　　　　　
Jun. 2018

ドラッグコンサルテーション デュラグルチド　　　　　　　　　　　　　　　
Apr. 2018

ドラッグコンサルテーション エボロクマブ　　　　　　　　　　　　　　　
Feb. 2018

ドラッグコンサルテーション レボチロキシンナトリウム　　　　　　　　　　　　　　　
Dec. 2017

ドラッグコンサルテーション 5-ASA製剤　　　　　　　　　　　　　　　
Oct. 2017

ドラッグコンサルテーション カペシタビン　　　　　　　　　　　　　　　
Aug. 2017

ドラッグコンサルテーション クロピドグレル　　　　　　　　　　　　　　　
Jun. 2017

ドラッグコンサルテーション メトトレキサート　　　　　　　　　　　　　　　
Apr. 2017

ドラッグコンサルテーション ベンラファキシン　　　　　　　　　　　　　　　
Feb. 2017

ドラッグコンサルテーション フルタイドディスカス　　　　　　　　　　　　　　　
Dec. 2016

ドラッグコンサルテーション イプラグロフロジン　　　　　　　　　　　　　　　
Oct. 2016

ドラッグコンサルテーション ワルファリン・アスピリン腸溶錠　　　　　　　　　　　　　　　
Apr. 2008

【Critical Care Nephrology-集中治療における腎疾患の重要性】ICUにおける腎不全合併時の薬物投与戦略
May 2017

【がん領域における注意すべき医薬品副作用のメカニズムと対応】抗がん剤による皮膚障害の発現機序と対策
Apr. 2014

拭き取り後のフルオロウラシル残留量を指標とした抗がん剤分解剤の有用性の検証　　　　　　　　　　　　　　　
Aug. 2025

がん薬物療法の副作用マネジメント　　　　　　　　　　　　　　　
Feb. 2025, [Invited]

新生児・乳児に対するカルシウム･リン製剤の 同時投与時における吸収量低下リスクの検討　　　　　　　　　　　　　　　
Nov. 2024

好酸球数の変動は免疫チェックポイント阻害剤による免疫関連有害事象を予測する有用なバイオマーカーとなる　　　　　　　　　　　　　　　
2021

前臨床で見出したバイオマーカー候補の臨床における有用性検証　　　　　　　　　　　　　　　
Oct. 2018

Novel serum biomarker candidates for gastric and/or duodenal ulcers in humans　　　　　　　　　　　　　　　
Aug. 2018

生体肝移植におけるアミノグリコシド系抗菌薬予防投与の有用性の検討　　　　　　　　　　　　　　　
May 2018

急性期病棟におけるファスジルによる薬物性肝障害リスク因子の解析　　　　　　　　　　　　　　　
2018

急性期病棟におけるタゾバクタム・ピペラシリンによる薬物性肝障害発症リスクの,性差を考慮した評価法の構築　　　　　　　　　　　　　　　
2018

薬剤師の立場からみた急性血液浄化療法の安全対策　　　　　　　　　　　　　　　
2017, [Invited]

Systems-pharmacological analysis of drug toxicities　　　　　　　　　　　　　　　
Hiroshi Suzuki; Takahiro Amemiya; Yoshiaki Kariya; Masashi Honma
The 21st International Symposium on Microsomes and Drug Oxidations, Oct. 2016

数理モデル解析を利用したキナーゼ阻害薬副作用発現機構の解析　　　　　　　　　　　　　　　
Sep. 2016

新生児・乳児におけるミダゾラムによる逆説的反応発現リスク因子の解析　　　　　　　　　　　　　　　
2015

リツキシマブによるインフュージョンリアクション発症リスク因子の解析　　　　　　　　　　　　　　　
2014

スニチニブによる副作用発現機構の解析　　　　　　　　　　　　　　　
2013

Mechanisms Of Adverse Effects Related To Sunitinib Treatment　　　　　　　　　　　　　　　
Jan. 2012

スニチニブによる肝機能障害発現機構の解析　　　　　　　　　　　　　　　
Oct. 2010

キナーゼ阻害薬による副作用とオフ・ターゲット阻害プロファイル　　　　　　　　　　　　　　　
Sep. 2010

キナーゼ阻害薬による副作用発現メカニズムの解析　　　　　　　　　　　　　　　
Dec. 2009

高カロリー輸液用総合ビタミン剤は透析患者の血清カルシウム値を上昇させる可能性がある　　　　　　　　　　　　　　　
2009

急性期医療における薬剤師のリスクマネジメントへの取り組み-ICU・CCU病棟における医薬品情報提供内容の解析-　　　　　　　　　　　　　　　
2008

急性期病棟における新人薬剤師の教育とその評価~フォローアップシートの作成と薬学的アプローチ~　　　　　　　　　　　　　　　
2007

遺伝的高血圧ラット培養脳ニューロンにおけるアンジオテンシンAT1受容体遺伝子発現:PKCベータの関与について　　　　　　　　　　　　　　　
2005

遺伝的高血圧ラット脳ニューロンにおけるプロテインキナーゼCサブタイプ遺伝子の発現について　　　　　　　　　　　　　　　
2004