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)

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)

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

  Kawakami, T; Masui, S; Onishi, A; Onizawa, H; Fujii, T; Murakami, K; Murata, K; Tanaka, M; Shimada, T; Nakagawa, S; Matsuda, S; Morinobu, A; Terada, T; Yonezawa, A

  MODERN RHEUMATOLOGY  2024.03

  Joint Work, Last author, Corresponding author, Accepted,  ISSN  1439-7595

  • 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.)  2024.01

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

  • Access to Document (DOI)

• Low serum concentrations of bevacizumab and nivolumab owing to excessive urinary loss in patients with proteinuria: a case series.

  Takashi Masuda, Taro Funakoshi, Takahiro Horimatsu, Shinya Yamamoto, Takeshi Matsubara, Sho Masui, Shunsaku Nakagawa, Yasuaki Ikemi, Motoko Yanagita, Manabu Muto, Tomohiro Terada, Atsushi Yonezawa

  Cancer chemotherapy and pharmacology （Cancer Chemotherapy and Pharmacology)   2024

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

  　View Summary

  PURPOSE: Proteinuria can cause interindividual variability in the pharmacokinetics of therapeutic antibodies and may affect therapeutic efficacy. Here, we measured the serum and urinary concentrations of bevacizumab (BV) and nivolumab (NIVO) in patients with proteinuria and reported a case series of these patients. METHODS: Thirty-two cancer patients who received BV every 3 weeks or NIVO every 2 weeks between November 2020 and September 2021 at Kyoto University Hospital were enrolled in this study. The serum and urinary concentrations of BV and NIVO were measured using liquid chromatography-tandem mass spectrometry. RESULTS: We divided the BV-treated patients and the NIVO-treated patients into two groups based on the urine protein-creatinine ratio (UPCR): UPCR 1 g/g or higher (BV, n = 9; NIVO, n = 3) and UPCR less than 1 g/g (BV, n = 14; NIVO, n = 6). Serum concentrations of the therapeutic antibodies adjusted by their doses were significantly lower in both BV- and NIVO-treated patients with UPCR 1 g/g or higher compared to those with less than 1 g/g. In patients with UPCR 1 g/g or higher, urinary concentrations of the therapeutic antibodies adjusted by their serum concentrations and urinary creatinine concentrations tended to increase. CONCLUSION: This case-series study suggests a possibility of reduction in serum concentrations of BV and NIVO in patients with proteinuria by urinary excretion of these drugs.

  • Access to Document (DOI)

• A case report of a prolonged decrease in tacrolimus clearance due to co-administration of nirmatrelvir/ritonavir in a lung transplant recipient receiving itraconazole prophylaxis

  Ayumi Tsuzawa, Yoshiki Katada, Keisuke Umemura, Mitsuhiro Sugimoto, Asami Nishikawa, Yu-ki Sato, Yuko Yoshida, Norikai Kitada, Atsushi Yonezawa, Daisuke Nakajima, Hiroshi Date, Tomohiro Terada

  Journal of Pharmaceutical Health Care and Sciences （Japanese Society of Pharmaceutical Health Care and Sciences)  9 （ 1 ） 12 2023.12

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

  　View Summary

  Background: Drug-drug interaction management is complex. Nirmatrelvir/ritonavir is a potent cytochrome P450 (CYP) 3A inhibitor and influences pharmacokinetics of co-administered drugs. Although there are several reports about drug-drug interactions of nirmatrelvir/ritonavir, an influence of a concomitant use of nirmatrelvir/ritonavir and another potent CYP3A inhibitor on tacrolimus remains unclear. Here, we experienced a lung transplant patient with the novel coronavirus disease 2019 (COVID-19). In this patient, nirmatrelvir/ritonavir was administered, and the inhibitory effect of itraconazole on CYP3A was prolonged. Case presentation: We present a case in forties who had undergone lung transplantation. He was administered itraconazole and tacrolimus 1.0 mg/d, with a trough value of 8–12 ng/mL. The patient contracted the COVID-19, and a nirmatrelvir/ritonavir treatment was initiated. During the antiviral treatment, tacrolimus administration was discontinued for 5 d. Tacrolimus was resumed at 1.0 mg/d after completion of the nirmatrelvir/ritonavir treatment, but the trough value after 7 d was high at 31.6 ng/mL. Subsequently, the patient was placed on another 36-h tacrolimus discontinuation, but the trough value decreased to only 16.0 ng/mL. Conclusions: Co-administration of ritonavir caused a prolonged decrease in tacrolimus clearance through its inhibitory effects on CYP3A in a patient taking itraconazole. Management of drug-drug interaction by pharmacists can be important for patients with multiple medications.

  • Access to Document (DOI)

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• 【"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

• 【難しい数式も、TDMもわからない!「ニガテさん」のための薬物動態】(第5章)相互作用が見抜ける!遺伝子多型がわかる!　トランスポーターの阻害による相互作用

  米澤 淳

  調剤と情報 ((株)じほう)  27 ( 10 ) 1797 - 1801 2021.07

  ISSN  1341-5212

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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

  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)

  　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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