KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2007.04

  -

  2013.05

  Kyoto University Hospital, 薬剤部, Assistant Professor

• 2013.06

  -

  2016.03

  Kyoto University Hospital, 薬剤部, Senior Lecturer

• 2014.10

  -

  2015.09

  Stanford University, Visiting Assistant Professor

• 2016.04

  -

  2023.03

  Kyoto University Hospital, Dept. of Pharmacy, Vice Director

• 2016.07

  -

  2023.03

  Kyoto University, Graduate School of Pharmaceutical Sciences, Associate Professor

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Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 1998.04

  -

  2002.03

  Kyoto University, 薬学部, 総合薬学科

  University, Graduated

• 2002.04

  -

  2004.03

  Kyoto University, 薬学研究科

  Graduate School, Completed, Master's course

• 2004.04

  -

  2007.03

  Kyoto University, 薬学研究科

  Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 博士（薬学）, Kyoto University, Coursework, 2007.03

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• 薬剤師免許, 2002.05

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Clinical pharmacy (臨床薬理学、薬物動態学)

Books 【 Display / hide 】

Books 【 Display / hide 】

• 薬剤業務補助者育成ガイドブック : 実践!タスクシフト

  松原 和夫, 矢野 育子, 大村 友博, 米澤 淳, 薬事日報社, 2024

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Development of extended pharmacokinetic models for propofol based on measured blood and brain concentrations.

  Masayoshi Kawata, Atsushi Yonezawa, Yohei Mineharu, Kotaro Itohara, Toshiyuki Mizota, Yoshihiro Matsui, Takayuki Kikuchi, Yukihiro Yamao, Etsuko Yamamoto Hattori, Miho Hamada, Daiki Hira, Keiko Furukawa, Susumu Miyamoto, Tomohiro Terada, Kazuo Matsubara, Yoshiki Arakawa

  Scientific reports (Scientific Reports)  14 ( 1 ) 6326 - 6326 2024.12

  Research paper (scientific journal), Joint Work, Corresponding author, Accepted,  ISSN  2045-2322

  　View Summary

  Propofol's pharmacokinetics have been extensively studied using human blood samples and applied to target-controlled infusion systems; however, information on its concentration in the brain remains scarce. Therefore, this study aimed to simultaneously measure propofol plasma and brain concentrations in patients who underwent awake craniotomy and establish new pharmacokinetic model. Fifty-seven patients with brain tumors or brain lesions who underwent awake craniotomy were sequentially assigned to model-building and validating groups. Plasma and brain (lobectomy or uncapping margins) samples were collected at five time-points. The concentration of propofol was measured using high-performance liquid chromatography. Population pharmacokinetic analysis was conducted through a nonlinear mixed-effects modeling program using a first-order conditional estimation method with interactions. Propofol's brain concentrations were higher than its plasma concentrations. The measured brain concentrations were higher than the effect site concentrations using the previous models. Extended models were constructed based on measured concentrations by incorporating the brain/plasma partition coefficient (Kp value). Extended models showed good predictive accuracy for brain concentrations in the validating group. The Kp value functioned as a factor explaining retention in the brain. Our new pharmacokinetic models and Kp value can predict propofol's brain and plasma concentrations, contributing to safer and more stable anesthesia.

  • Access to Document (DOI)

• Subjective symptoms are triggers for the detection of immune checkpoint inhibitor-induced interstitial lung disease and associate with disease severity: a single-center retrospective study

  Mari Yokoi, Atsushi Yonezawa, Daiki Hira, Tomohiro Handa, Kiminobu Tanizawa, Shunsaku Nakagawa, Masahiro Tsuda, Yasuaki Ikemi, Ryo Itotani, Hironori Yoshida, Motoo Nomura, Junichi Matsubara, Kosaku Murakami, Hiroaki Ozasa, Manabu Muto, Tomohiro Terada

  Journal of Pharmaceutical Health Care and Sciences (Springer Science and Business Media LLC)  10 ( 1 ) 52 2024.12

  Research paper (scientific journal), Joint Work, Corresponding author, Accepted,  ISSN  2055-0294

  　View Summary

  Abstract
  
  Background
  
  Interstitial lung disease (ILD) is one of the most common fatal immune-related adverse events (irAEs). ILD development adversely affects the continuation of anticancer drug therapy, including immune checkpoint inhibitor (ICI) therapy and prognosis. There are no established useful clinical indicators for the early detection of ILD. Furthermore, the factors that lead the attending physician to suspect ICI-induced ILD (ICI-ILD) remain unclear. This study aimed to investigate the ICI-ILD detection based on subjective symptoms and their relationship with disease severity in patients receiving anti-PD-1/PD-L1 antibody.
  
  Methods
  
  This was a retrospective observational study. We enrolled the patients who received anti-PD-1/PD-L1 antibody at Kyoto University Hospital between September 2014 and April 2021. Patients who developed ICI-ILD were stratified into two distinct groups based on factors that triggered the suspicion of ILD development. The “Subjective symptoms” group was defined as patients in whom ILD was detected based on subjective symptoms. Conversely, the “Routine examinations” group was defined as patients in whom ILD was suspected based on scheduled routine examinations. The severity of ILD in each group was assessed and its association with changes in the respiratory symptoms was examined.
  
  Results
  
  Of 926 patients who received anti-PD-1/PD-L1 antibody, 51 patients (5.5%) developed ICI-ILD. The incidence of ICI-ILD in patients with lung cancer was significantly higher than that in patients with other cancers (P < 0.001). Among the patients with ICI-ILD, 27 patients (52.9%) were classified into the “Subjective symptoms” group. The “Subjective symptoms” group exhibited a significantly higher proportion of Grade 3–5 ICI-ILD cases than the “Routine examinations” group (76.2% vs. 23.8%, P = 0.010). At the last visit, before the suspected onset of ILD, 21 of the 27 patients (77.8%) had no symptoms or no change in the respiratory symptoms.
  
  Conclusion
  
  Subjective symptoms triggered the suspicion of Grade 3–5 ICI-ILD. Enhanced monitoring and patient education could be essential for the early detection of ICI-ILD because ILD may develop rapidly. Our findings might help to manage ICI-ILD in clinical practice.

  • Access to Document (DOI)

• Population Pharmacokinetic Modeling of Posaconazole in Japanese Patients Receiving Fungal Prophylaxis.

  Mitsuhiro Sugimoto, Atsushi Yonezawa, Junya Kanda, Kotaro Itohara, Daiki Hira, Takeo Yamagiwa, Risa Taniguchi, Yuta Hanyu, Mizuki Watanabe, Yasuyuki Arai, Chisaki Mizumoto, Toshio Kitawaki, Tadakazu Kondo, Kouhei Yamashita, Akifumi Takaori-Kondo, Tomohiro Terada

  Therapeutic drug monitoring 46 ( 5 ) 611 - 618 2024.04

  Research paper (scientific journal), Joint Work, Corresponding author, Accepted,  ISSN  0163-4356

  　View Summary

  BACKGROUND: Posaconazole is a vital drug to treat and prevent invasive fungal infections. Several factors, such as sex, body weight, total serum proteins, dietary intake, and severe mucositis, affect posaconazole pharmacokinetics (PKs). However, the relevance of other factors that affect the PKs of posaconazole in hematopoietic stem cell transplantation (HSCT) is unknown. This study explored factors influencing the PKs of posaconazole in HSCT recipients and nontransplant patients with hematological diseases. METHODS: The authors conducted a single-institution, retrospective study. Forty-two Japanese inpatients receiving oral posaconazole tablets as prophylaxis for fungal infections were enrolled in this study. A one-compartment model with first-order absorption was used as the structural pharmacokinetic model. A population PK (PopPK) analysis was performed using a nonlinear mixed-effects modeling program, using a first-order conditional estimation method with interactions. Perl-speaks-NONMEM and R were used to evaluate the goodness of fit and visualize the output. RESULTS: In 29% of the enrolled patients, the serum concentration of posaconazole was <0.5 mcg/mL, considered the effective range. PopPK analysis revealed that the patient had undergone HSCT within 1 year, diarrhea occurred more than 5 times a day, and aspartate aminotransferase were covariates that influenced apparent clearance (CL/F). The CL/F of posaconazole was 1.43-fold higher after HSCT and 1.26-fold higher during diarrhea. CONCLUSIONS: PopPK analysis revealed that HSCT, diarrhea, and aspartate aminotransferase were factors associated with the CL/F of posaconazole. The trough concentration of posaconazole may be below the therapeutic range in a few patients with diarrhea and/or after HSCT. As invasive fungal infections in patients with hematologic diseases can be life-threatening, therapeutic drug monitoring of posaconazole is strongly recommended, and patients should be carefully monitored.

  • Access to Document (DOI)

• Comparison of safety and effectiveness between etanercept biosimilar LBEC0101 and reference in patients with rheumatoid arthritis in real-world data using the KURAMA cohort.

  Tomoya Kawakami, Sho Masui, Akira Onishi, Hideo Onizawa, Takayuki Fujii, Kosaku Murakami, Koichi Murata, Masao Tanaka, Takashi Shimada, Shunsaku Nakagawa, Shuichi Matsuda, Akio Morinobu, Tomohiro Terada, Atsushi Yonezawa

  Modern rheumatology 34 ( 6 ) 1135 - 1141 2024.03

  Research paper (scientific journal), Joint Work, Last author, Corresponding author, Accepted,  ISSN  1439-7595

  　View Summary

  OBJECTIVES: Biosimilars are anticipated to be widely used in the treatment of rheumatoid arthritis (RA), owing to their cost efficiency; LBEC0101 was the first etanercept (ETN) biosimilar approved in Japan. However, there are limited real-world data comparing its safety and effectiveness with those of a reference product. METHODS: This study used data from the Kyoto University Rheumatoid Arthritis Management Alliance cohort, including patients with RA who received ETN therapy-ETN reference product (ETN-RP) or LBEC0101-between 2015 and 2021. Serum ETN levels were measured using liquid chromatography-tandem mass spectrometry. RESULTS: The 1-year continuation rates of ETN-RP and LBEC0101 were 58.7% and 74.4%, respectively. Effectiveness of treatment was evaluated in 18 patients; both products significantly reduced the 28-joint RA disease activity score and erythrocyte sedimentation rate (DAS28-ESR). Moreover, to determine equivalence, we analysed 11 patients who switched from ETN-RP to LBEC0101; the DAS28-ESR and serum ETN levels before and after switching were not significantly different. CONCLUSIONS: This real-world cohort study confirmed that the biosimilar of ETN, LBEC0101, was comparable to the reference product in terms of continuation rate, effectiveness at initiation of introduction, and effect persistence before and after switching in clinical practice.

  • Access to Document (DOI)

• Clinical characteristics of cryopyrin-associated periodic syndrome and long-term real-world efficacy and tolerability of canakinumab in Japan: results of a nationwide survey.

  Miyamoto T, Izawa K, Masui S, Yamazaki A, Yamasaki Y, Matsubayashi T, Shiraki M, Ohnishi H, Yasumura J, Tomohiro K, Miyamae T, Matsubara T, Arakawa N, Ishige T, Takizawa T, Shimbo A, Shimizu M, Kimura N, Maeda Y, Maruyama Y, Shigemura T, Furuta J, Sato S, Tanaka H, Izumikawa M, Yamamura M, Hasegawa T, Kaneko H, Nakagishi Y, Nakano N, Iida Y, Nakamura T, Wakiguchi H, Hoshina T, Kawai T, Murakami K, Akizuki S, Morinobu A, Ohmura K, Eguchi K, Sonoda M, Ishimura M, Furuno K, Kashiwado M, Mori M, Kawahata K, Hayama K, Shimoyama K, Sasaki N, Ito T, Umebayashi H, Omori T, Nakamichi S, Dohmoto T, Hasegawa Y, Kawashima H, Watanabe S, Taguchi Y, Nakaseko H, Iwata N, Kohno H, Ando T, Ito Y, Kataoka Y, Saeki T, Kaneko U, Murase A, Hattori S, Nozawa T, Nishimura K, Nakano R, Watanabe M, Yashiro M, Nakamura T, Komai T, Kato K, Honda Y, Hiejima E, Yonezawa A, Bessho K, Okada S, Ohara O, Takita J, Yasumi T, Nishikomori R, Japan CAPS working group

  Arthritis & rheumatology (Hoboken, N.J.) (Arthritis and Rheumatology)  76 ( 6 ) 949 - 962 2024.01

  Research paper (scientific journal), Joint Work, Accepted,  ISSN  2326-5191

  　View Summary

  Objective: We assess the clinical characteristics of patients with cryopyrin-associated periodic syndrome (CAPS) in Japan and evaluate the real-world efficacy and safety of interleukin-1 (IL-1) inhibitors, primarily canakinumab. Methods: Clinical information was collected retrospectively, and serum concentrations of canakinumab and cytokines were analyzed. Results: A total of 101 patients were included, with 86 and 15 carrying heterozygous germline and somatic mosaic mutations, respectively. We identified 39 mutation types, and the common CAPS-associated symptoms corresponded with those in previous reports. Six patients (5.9% of all patients) died, with four of the deaths caused by CAPS-associated symptoms. Notably, 73.7% of patients (100%, 79.6%, and 44.4% of familial cold autoinflammatory syndrome, Muckle–Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem inflammatory disease, respectively) achieved complete remission with canakinumab, and early therapeutic intervention was associated with better auditory outcomes. In some patients, canakinumab treatment stabilized the progression of epiphysial overgrowth and improved height gain, visual acuity, and renal function. However, 23.7% of patients did not achieve inflammatory remission with crucial deterioration of organ damage, with two dying while receiving high-dose canakinumab treatment. Serological analysis of canakinumab and cytokine concentrations revealed that the poor response was not related to canakinumab shortage. Four inflammatory nonremitters developed inflammatory bowel disease (IBD)—unclassified during canakinumab treatment. Dual biologic therapy with canakinumab and anti–tumor necrosis factor-α agents was effective for IBD– and CAPS-associated symptoms not resolved by canakinumab monotherapy. Conclusion: This study provides one of the largest epidemiologic data sets for CAPS. Although early initiation of anti–IL-1 treatment with canakinumab is beneficial for improving disease prognosis, some patients do not achieve remission despite a high serum concentration of canakinumab. Moreover, IBD may develop in CAPS after canakinumab treatment. (Figure presented.).

  • Access to Document (DOI)

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• 広報出版部特別座談会　病院薬剤師による研究活動　なぜ私たちは研究をするのか(後編)

  大野 能之, 安 武夫, 米澤 淳, 小林 一男, 那須 いずみ, 村上 修太郎

  東京都病院薬剤師会雑誌 ((一社)東京都病院薬剤師会)  73 ( 3 ) 131 - 138 2024.05

  ISSN  1345-7624

• 【"糖鎖とDDS"】糖鎖が抗体医薬品を運ぶ

  米澤 淳

  Drug Delivery System (日本DDS学会)  38 ( 4 ) 297 - 304 2023.09

  ISSN  0913-5006

  　View Summary

  抗体医薬品は医療において極めて重要な役割を果たしている。Fc領域の297番目のアスパラギン残基にはN-結合型糖鎖が結合しており、薬力学および薬物動態において重要な役割を果たす。特に、末端ガラクトース、シアル酸、フコースなどは、抗体依存性細胞傷害(ADCC)、補体依存性細胞傷害(CDC)、肝取り込みに影響することが知られている。すなわち、糖鎖が抗体医薬品を運んでいる。他方、抗体医薬品の測定は主に酵素結合免疫吸着検査法(ELISA法)が用いられており、糖鎖の変化などは区別できない。しかし、抗体医薬品も生体内での構造変化(バイオトランスフォーメーション)が起こることが明らかにされつつある。そこで、質量分析技術を用いた新たな分析手法が注目されている。本稿では、抗体医薬品における糖鎖の役割に加えて、筆者らの研究成果を紹介する。(著者抄録)

• 【抗体医薬の進歩と課題】臨床における最新動向　抗体医薬品の血中濃度モニタリング

  米澤 淳

  医学のあゆみ (医歯薬出版(株))  285 ( 10 ) 960 - 964 2023.06

  ISSN  0039-2359

  　View Summary

  薬物血中濃度モニタリング(TDM)は抗菌薬,抗てんかん薬,免疫抑制薬などの個別化医療に大きく貢献してきた.抗体医薬品は免疫原性を有し血中濃度の個人差も現れることから,TDMの導入が期待されている.近年,関節リウマチ患者におけるインフリキシマブ血中濃度評価が承認された.しかし,低分子医薬品と同じように有効域を目指した投与設計を行うわけではなく,どのように実臨床で活用していくかの課題が残る.従来のproactive TDMに加えて,イベント発生時に行うreactive TDMという考え方も生まれ,抗体医薬品TDMの新しい考え方か展開されていく.また,抗体医薬品の革新的な分析手法の開発や,バイオトランスフォーメーションのエビデンスも蓄積されており,さらなる研究展開が進んでいる.本稿では,抗体医薬品のTDMの現状と今後の展望を概説するとともに,抗体医薬品の測定法の開発についてもも述べる.(著者抄録)

• 【気になるがん治療の最新Topics】がん治療におけるバイオシミラー

  米澤 淳

  薬事 ((株)じほう)  65 ( 6 ) 1082 - 1086 2023.05

  ISSN  0016-5980

  　View Summary

  ＜Key Point＞●バイオシミラーは先行バイオ医薬品と有効成分がまったく同じものではないため,同等性・同質性を検証する品質評価や臨床試験を実施して開発されている。●バイオ医薬品は高額であるため,バイオシミラーの使用は医療費削減に貢献する。●バイオシミラーのさらなる使用促進が課題である。●より良いバイオシミラーの開発が期待される。(著者抄録)

• 【Onco-nephrology:悪性腫瘍治療と腎機能障害】CKD患者における抗がん薬治療　蛋白尿・低アルブミン血症患者へのがん薬物療法

  北村 寛, 桑原 孝成, 米澤 淳, 加藤 大悟

  腎と透析 ((株)東京医学社)  92 ( 3 ) 567 - 572 2022.03

  ISSN  0385-2156

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• Analysis of biotransformation in therapeutic antibody

  2023.04

  -

  2027.03

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

  　View Summary

  近年、研究代表者らは一部の抗体医薬品が生体内において、糖鎖の変化、アミノ酸の脱アミド化、末端アミノ酸切断など生体内での構造変化（バイオトランスフォーメーション）を発見している。本研究では、抗体医薬品のバイオトランスフォーメーションの実態を解明し臨床的意義を明らかにすることを目的とする。関節リウマチ患者を対象としたKURAMAコホートを用い、研究代表者らにより確立された独自の測定技術を活用する。さらに、バイオトランスフォーメーションの臨床効果への影響について疫学専門家による臨床情報の解析も実施する。本研究により抗体医薬品の真の体内動態が明らかになり臨床効果の説明が可能となることが期待される。

• Basic and clinical analysis of anti-drug antibody against therapeutic antibody

  2019.04

  -

  2023.03

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Yonezawa Atsushi, Grant-in-Aid for Scientific Research (B), Principal investigator

  　View Summary

  Unlike conventional low-molecular-weight drugs, therapeutic antibody has immunogenicity, and anti-drug antibodies are produced in the body. In this study, we clarified the characteristics of anti-drug antibodies against various therapeutic antibodies, investigated the effects on clinical efficacy and on the pharmacokinetics of therapeutic antibodies in patients with autoimmune diseases. Although the production of anti-drug antibodies is observed in many therapeutic antibodies, their characteristics varied, such as reducing the blood concentration of therapeutic antibody, some not, and others depending on the measurement method. The clinical effect has stronger correlation with the blood concentration of therapeutic antibody. In addition, biotransformation of therapeutic antibodies was also discovered.

• Phathological analysis of RFVT knockout mice

  2015.04

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  2018.03

  Grants-in-Aid for Scientific Research, Yonezawa Atsushi, Grant-in-Aid for Scientific Research (C), Principal investigator

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  Riboflavin (Vitamin B2) is a orange-yellow water-soluble vitamin, which plays important roles in the metabolism of glucose, amino acids and lipids. In the present study, we analyzed the pathology of the disruption in riboflavin transporter RFVT gene. It was revealed that the disruption of RFVT gene induced metabolic disorders, caused by riboflavin deficiency, in mice. These results will contribute to the development of therapy in RFVT-genetic rare diseases.

• Individualized L-dopa therapy in patients with Parkinson's disease

  2012.04

  -

  2015.03

  Grants-in-Aid for Scientific Research, MATSUBARA Kazuo, YONEZAWA Atsushi, FUKUDO Masahide, OMURA Tomohiro, NAKAGAWA Shunsaku, Grant-in-Aid for Scientific Research (C), Coinvestigator(s)

  　View Summary

  L-dopa remains the gold standard for treating Parkinson's disease (PD); however, long-term L-dopa treatment is associated with motor adverse effects, particularly wearing-off. Entacapone prevents catechol-O-methyltransferase (COMT) from metabolizing L-dopa into 3-methoxy-4-hydroxy-L-phenylalanine in the periphery and ameliorates wearing-off in patients with PD treated with L-dopa for a prolonged period. In the present study, we examined whether the blood concentration of L-dopa was affected by COMT gene polymorphisms in patients taking L-dopa concomitantly with entacapone.
  We demonstrated that entacapone did not change the area under the blood concentration-time curve of L-dopa in PD patient who had a low-activity COMT gene. This result suggests that the blood concentration of L-dopa taken concomitantly with entacapone is affected by the COMT gene polymorphism.

• Pathophysiology of riboflavin transporter deficiency for developing therapeutic drugs

  2012.04

  -

  2015.03

  Grants-in-Aid for Scientific Research, YONEZAWA Atsushi, Grant-in-Aid for Scientific Research (C), Principal investigator

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  In the present study, we carried out in vitro, in vivo and clinical investigations in order to clarify the pathology of riboflavin transporter (RFVT) deficiency. The data using the mice and culture cells showed that RFVT2 is expressed in the small intestine and mediates the uptake of riboflavin into intestinal epithelial cells. In addition, in the collaboration with foreign groups, it was suggested that the deficiency of RFVT2 as well as RFVT3 causes Brown-Vialetto-Van Laere syndrome (BVVLS). These results can help to clarify the pathology and develop the therapeutic strategy for BVVLS.

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Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• THAI PHARMACY EXPERIENCE

  2024

• STUDY OF MAJOR FIELD(INTEGRATIVE CLINICAL PHARMACOLOGY)

  2024

• STUDY OF MAJOR FIELD: (CLINICAL PHARMACOKINETICS)

  2024

• SEMINAR(INTEGRATIVE CLINICAL PHARMACOLOGY)

  2024

• RESEARCH FOR BACHELOR'S THESIS 1

  2024

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