Yonezawa, Atsushi

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 統合臨床薬理学講座 ( Shiba-Kyoritsu )

Position

Professor

External Links

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

  • 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

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

Licenses and Qualifications 【 Display / hide

  • 薬剤師免許, 2002.05

 

Research Areas 【 Display / hide

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

 

Books 【 Display / hide

Papers 【 Display / hide

  • Population pharmacokinetic analysis of bevacizumab in Japanese cancer patients with proteinuria: a prospective cohort study.

    Takashi Masuda, Taro Funakoshi, Takahiro Horimatsu, Sho Masui, Daiki Hira, Marin Inoue, Kodai Yajima, Shunsaku Nakagawa, Yasuaki Ikemi, Junzo Hamanishi, Atsushi Takai, Shinya Yamamoto, Takeshi Matsubara, Masaki Mandai, Hiroshi Seno, Motoko Yanagita, Manabu Muto, Tomohiro Terada, Atsushi Yonezawa

    Cancer chemotherapy and pharmacology 95 ( 1 ) 46 - 46 2025.12

    Research paper (scientific journal), Joint Work, Last author, Corresponding author, Accepted,  ISSN  03445704

     View Summary

    PURPOSE: Bevacizumab (BV) is an effective therapeutic antibody utilized in various cancers. Serum BV concentration can be a factor that potentially affects its therapeutic efficacy. Although proteinuria could affect BV pharmacokinetics, its influence was not evaluated in the previous population pharmacokinetic (PopPK) studies. Because BV can cause proteinuria as an adverse event, the present study aimed to develop a PopPK model in patients with proteinuria and to evaluate the influence of proteinuria on BV pharmacokinetics. METHODS: This prospective cohort study enrolled 70 Japanese cancer patients newly starting BV, and 368 concentration samples from these patients were analyzed. Serum BV concentrations were measured at several time points including at the onset of proteinuria. PopPK analysis was conducted using a non-linear mixed-effects modeling program. A two-compartment model was used to estimate total body clearance (CL). RESULTS: Serum BV concentrations divided by the dose per body weight and dosing interval tended to be lower in patients with higher urinary protein to creatinine ratio (UPCR). The covariate analysis showed that increasing BV CL was associated with decreasing serum albumin concentration and increasing body weight and UPCR. The simulated median trough concentrations of BV in patients with Common Terminology Criteria for Adverse Events grades 1, 2, and 3 proteinuria were decreased by 12.0%, 20.6%, and 31.5%, respectively, compared to those in patients with grade 0. CONCLUSION: We successfully established a PopPK model incorporating UPCR to predict serum BV concentrations in patients with proteinuria. Our study provides additional insights to better understand BV pharmacokinetics.

  • Questionnaire Survey on the Needs of Outpatients Receiving Cancer Treatment Regarding Hospital Pharmacists:

    Sugimoto Mitsuhiro, Yonezawa Atsushi, Ikemi Yasuaki, Ikuta Keiko, Okada Hiroshi, Manaka Akihiro, Naganawa Hanako, Saigo Mamiko, Ogawa Akihiro, Iihara Hirotoshi, Miyake Tomohiro, Suzuki Akio, Terada Tomohiro

    Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) (Japanese Society of Pharmaceutical Health Care and Sciences)  51 ( 10 ) 605 - 613 2025.10

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1346342X

     View Summary

    <p>Hospital pharmacists can reduce the burden on physicians and improve the quality of cancer chemotherapy through task shifting and task sharing in cancer treatment. However, the specific needs and expectations of patients toward hospital pharmacists have not yet been clarified. We conducted an anonymous, self-administered questionnaire survey to assess the types of requests hospital pharmacists have for patients undergoing outpatient cancer treatment. A total of 310 outpatients with cancer attending Kyoto University Hospital, Gifu University Hospital, or Ise Red Cross Hospital were surveyed. The questionnaire response rate was 78.7%. The questionnaire survey revealed that approximately 30% of the patients were unable to fully communicate their wishes to medical doctors, and most of them preferred to consult with hospital pharmacists. The primary request of the patients for hospital pharmacists was an explanation about the adverse effects related to cancer treatment and anticancer drugs. There was also a high demand for advice on daily life precautions, lifestyle habits, and consultations on issues that patients feel unable to discuss with their primary doctor. However, some patients are still unable to consult with either their doctor or pharmacist. Therefore, there is a strong expectation for establishing a system that allows patients to consult with hospital pharmacists in outpatient cancer care. In conclusion, outpatient patients with cancer have a high need for hospital pharmacists. Hospital pharmacists must secure time to meet outpatients and effectively promote task shifting/sharing that benefits both medical doctors and patients.</p>

  • Identification and Physiological Analysis of Novel Riboflavin Transporter RFVT

    Yonezawa Atsushi

    Biological and Pharmaceutical Bulletin (The Pharmaceutical Society of Japan)  48 ( 7 ) 951 - 956 2025.07

    Lead author, Last author, Corresponding author, Accepted,  ISSN  09186158

     View Summary

    <p>Riboflavin (vitamin B2) is an essential water-soluble vitamin that serves as a precursor for flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), key cofactors in biological redox reactions. These reactions are crucial for energy metabolism and cellular homeostasis. Mammals cannot synthesize riboflavin and rely on specialized transport systems for its absorption and distribution. The discovery of the riboflavin transporter (RFVT) family, comprising RFVT1 (SLC52A1), RFVT2 (SLC52A2), and RFVT3 (SLC52A3) has provided critical insights into riboflavin homeostasis. These transporters show tissue-specific expression and play essential roles in riboflavin uptake. Mutations in SLC52A2 and SLC52A3 have been linked to Brown–Vialetto–Van Laere syndrome (BVVLS), a rare neurodegenerative disorder characterized by progressive sensorineural hearing loss and cranial nerve dysfunction. Functional studies using knockout mouse models have demonstrated that Rfvt deficiency results in embryonic lethality or severe neurological impairment due to impaired riboflavin transport. Patients with BVVLS and RFVT mutations showed symptomatic improvement with high-dose riboflavin supplementation. This review summarizes the molecular characteristics, physiological functions, and pathological implications of RFVTs and emphasizes their role in disease mechanisms and potential therapeutic strategies. Understanding the riboflavin transport mechanisms provides a foundation for developing targeted treatments for riboflavin-related disorders.</p>

  • Effectiveness of posaconazole as primary prophylaxis in allogeneic hematopoietic stem cell transplantation

    Hanyu Y., Kanda J., Sugimoto M., Iwasaki M., Watanabe M., Arai Y., Mizumoto C., Kitawaki T., Yamashita K., Yamagiwa T., Taniguchi R., Nakagawa S., Yonezawa A., Terada T., Takaori-Kondo A.

    International Journal of Hematology  2025

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  09255710

     View Summary

    We retrospectively analyzed the effectiveness of posaconazole (tablet and infusion formulations) and its correlation with blood concentration in preventing invasive fungal infections (IFIs) in 360 patients who underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) between 2010 and 2023. A total of 61 patients received posaconazole, 102 received micafungin, and 197 received fluconazole for primary prophylaxis. By day 100 post-transplant, the cumulative incidence of IFIs was significantly lower with posaconazole (5.0%) compared with fluconazole (14.4%) or micafungin (16.9%). Multivariate analysis showed that the risk of IFIs was significantly higher with fluconazole/micafungin than with posaconazole (hazard ratio 4.04, 95% CI 1.17–13.94, P = 0.027). This difference was most notable among patients with lymphoid malignancies (P = 0.053) and those undergoing repeat transplantation (P = 0.024). There were no significant differences in overall survival, non-relapse mortality, or mortality from IFI. Mean blood levels of posaconazole dropped to 0.57 μg/mL two weeks after allo-HSCT, coinciding with the observation of most IFIs in the posaconazole group shortly after transplant. Posaconazole appears to be more effective than fluconazole or micafungin as primary prophylaxis against IFIs in allo-HSCT recipients.

  • 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.

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Papers, etc., Registered in KOARA 【 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

  • Analysis of biotransformation in therapeutic antibody

    2023.04
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    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

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    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)

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    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

  • STUDY OF MAJOR FIELD: (CLINICAL PHARMACOKINETICS)

    2025

  • STUDY OF MAJOR FIELD(INTEGRATIVE CLINICAL PHARMACOLOGY)

    2025

  • SEMINAR(INTEGRATIVE CLINICAL PHARMACOLOGY)

    2025

  • RESEARCH FOR BACHELOR'S THESIS 1

    2025

  • PRE-CLINICAL TRAINING FOR HOSPITAL & COMMUNITY PHARMACY

    2025

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