米澤　淳 (ヨネザワ　アツシ)

Yonezawa, Atsushi

写真a

所属（所属キャンパス）

薬学部 薬学科 （芝共立）

職名

教授

外部リンク
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経歴 【 表示 ／ 非表示 】

  • 2007年04月
    -
    2013年05月

    京都大学医学部附属病院, 薬剤部, 助教

  • 2013年06月
    -
    2016年03月

    京都大学医学部附属病院, 薬剤部, 講師

  • 2014年10月
    -
    2015年09月

    Stanford University, Visiting Assistant Professor

  • 2016年04月
    -
    2023年03月

    京都大学医学部附属病院, 薬剤部, 副部長

  • 2016年07月
    -
    2023年03月

    京都大学大学院, 薬学研究科, 准教授

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学歴 【 表示 ／ 非表示 】

  • 1998年04月
    -
    2002年03月

    京都大学, 薬学部, 総合薬学科

    大学, 卒業

  • 2002年04月
    -
    2004年03月

    京都大学, 薬学研究科

    大学院, 修了, 修士

  • 2004年04月
    -
    2007年03月

    京都大学, 薬学研究科

    大学院, 修了, 博士

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学位 【 表示 ／ 非表示 】

  • 博士（薬学）, 京都大学, 課程, 2007年03月

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免許・資格 【 表示 ／ 非表示 】

  • 薬剤師免許, 2002年05月

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研究分野 【 表示 ／ 非表示 】

  • ライフサイエンス / 医療薬学 (臨床薬理学、薬物動態学)

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論文 【 表示 ／ 非表示 】

  • 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

    Tsuzawa A., Katada Y., Umemura K., Sugimoto M., Nishikawa A., Sato Y.k., Yoshida Y., Kitada N., Yonezawa A., Nakajima D., Date H., Terada T.

    Journal of Pharmaceutical Health Care and Sciences （Journal of Pharmaceutical Health Care and Sciences)  9 （ 1 ）  2023年12月

    筆頭著者, 最終著者, 責任著者, 査読有り

    　概要を見る

    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.

  • Preparation and pharmaceutical properties of Hangeshashinto oral ointment and its safety and efficacy in Syrian hamsters with 5-fluorouracil-induced oral mucositis

    Ogihara T., Kagawa M., Yamanaka R., Imai S., Itohara K., Hira D., Nakagawa S., Yonezawa A., Ito M., Nakagawa T., Terada T., Matsubara K.

    Journal of Natural Medicines （Journal of Natural Medicines)  77 （ 1 ） 53 - 63 2023年01月

    筆頭著者, 最終著者, 責任著者, 査読有り,  ISSN  13403443

    　概要を見る

    Chemotherapy-induced oral mucositis (COM) is a common adverse effect of cancer chemotherapy. Several clinical studies reported that repetitive use of mouthwashes containing 2.5–6.25% Hangeshashinto (HST), a Kampo formula, relieves COM, but the effect is insufficient. To solve this problem, we produced an oral ointment of 12% HST extract (considered quantitatively equivalent to 20% commercially available HST), which will increase the local concentrations of its active ingredients and prolong the contact time with COM. In this study, we evaluated the pharmaceutical properties (spreadability and stability) of HST oral ointment. In addition, its safety (oral mucosal irritation) and therapeutic effects on 5-fluorouracil-induced oral mucositis were evaluated in male Syrian hamsters. The HST ointment showed good spreadability and stability for more than 8 weeks at 4 °C. In the oral mucosal irritation test, topical application of HST ointment (0.2 g) three times per day for 14 days had no adverse effect on the oral mucosa of hamsters. In hamsters treated with 5-fluorouracil (60 mg/kg) twice, COM was induced by a submucosal injection of 5% acetic acid into the cheek pouch. When HST ointment (50 µg) was topically applied to the mucositis area once per day for 12 days, the area and macroscopic score of mucositis were significantly decreased, and the depth of the wound tended to be reduced compared with the lactose ointment-treated control animals. These findings suggest that HST oral ointment shows good properties in spreadability, stability, and safety, and elicits a therapeutic effect in an animal model of COM. Graphical abstract: [Figure not available: see fulltext.]

  • Effect of Severe Renal Dysfunction on the Plasma Levels of DNA-Reactive Platinum after Oxaliplatin Administration

    Nakagawa S., Shimazaki A., Funakoshi T., Yonezawa A., Kataoka S., Horimatsu T., Hira D., Itohara K., Imai S., Nakagawa T., Matsubara T., Yanagita M., Muto M., Matsubara K., Terada T.

    Biological and Pharmaceutical Bulletin （Biological and Pharmaceutical Bulletin)  46 （ 2 ） 194 - 200 2023年

    筆頭著者, 最終著者, 責任著者, 査読有り,  ISSN  09186158

    　概要を見る

    Higher amounts of circulating ultrafilterable platinum (fPt) are found in patients with renal dysfunction receiving a constant dose of oxaliplatin. However, the increased systemic fPt levels do not increase oxaliplatin-induced toxicities. We hypothesized that renal dysfunction has minimal effect on the elimination rate of reactive fPt, and that the DNA-binding capacity is one of the properties of reactive Pt species. This study aimed to quantify DNA-reactive fPt in plasma and to evaluate the impact of severe renal dysfunction on its pharmacokinetics. The pharmacokinetics of oxaliplatin was assessed in rats with bilateral nephrectomy (BNx) and in a hemodialysis patient who received mFOLFOX7 therapy for advanced metastatic gastric cancer. The platinum concentrations were determined using inductively coupled plasma-mass spectrometry. The amount of DNA-reactive fPt in the plasma was evaluated by the reaction between plasma and calf thymus DNA. Compared to the sham group in rats, the BNx group had significantly higher plasma total fPt concentrations at 24 h after drug administration. However, there was no significant difference in the plasma levels of DNA-reactive fPt between the two groups. In a hemodialysis patient, the plasma levels of total fPt decreased to 35.9 and 7.3% at 2 and 14 d after treatment, respectively. The plasma level of DNA-reactive fPt also decreased to 1.9 and 0.6%, respectively, on these days. This study showed that severe renal dysfunction has a limited effect on the plasma levels of DNA-reactive fPt after oxaliplatin administration.

  • Association between time in therapeutic range of tacrolimus blood concentration and acute rejection within the first three months after lung transplantation

    Katada Y., Nakagawa S., Itohara K., Suzuki T., Kato R., Endo H., Sugimoto M., Yonezawa A., Nakagawa T., Ohsumi A., Nakajima D., Date H., Terada T.

    Journal of Pharmaceutical Health Care and Sciences （Journal of Pharmaceutical Health Care and Sciences)  8 （ 1 ）  2022年12月

    筆頭著者, 最終著者, 責任著者, 査読有り

    　概要を見る

    Background: Tacrolimus is a key drug in immunosuppressive therapy following lung transplantation. The blood tacrolimus levels are likely to fluctuate in the early postoperative period, and failure to maintain the tacrolimus trough level in target ranges is a risk factor for rejection. However, there is little information about the relationship between the time in therapeutic range (TTR) of the tacrolimus trough level (tacrolimus TTR) and clinical outcomes. This study aimed to evaluate the association between tacrolimus TTR and acute rejection (AR) within the first three months after lung transplantation. Methods: This was a retrospective study of patients who underwent lung transplantation at a single center. The target tacrolimus trough levels were 10–15 ng/mL, and tacrolimus TTR was calculated using the Rosendaal method. The cut-off value of the tacrolimus TTR was estimated by receiver operating characteristic analysis based on AR. Results: The study included 90 patients. AR was observed in 26 patients. In this study, ‘‘early-AR’’ was defined as any AR within 2 weeks post-transplant (n = 22) and ‘‘late-AR’’ was defined as any AR after 1-month post-transplant (n = 4). For early AR, the relationship between tacrolimus TTR and the onset of AR was examined. There were no differences in the tacrolimus TTR between the early-AR group and non-AR group (35.7 ± 22.4 vs 31.5 ± 19.9%, P = 0.416). For late-AR, the relationship with tacrolimus TTR was examined every 10 d. The tacrolimus TTR during postoperative days (POD) 21–30 and POD 31–onset was significantly lower in the late-AR group than the no-AR group (50.0 ± 7.1 vs. 71.8 ± 18.0% and 37.0 ± 26.6 vs. 68.9 ± 31.5%, P < 0.05, respectively). The cutoff value of the tacrolimus TTR during POD 21–30 was estimated as 55.0%. Conclusions: Our findings suggest that a lower tacrolimus TTR is a predictor of late AR. A tacrolimus TTR of 55% or higher is necessary to reduce the risk of AR during this period after lung transplantation.

  • Use of proton pump inhibitors and macrolide antibiotics and risk of acute kidney injury: a self-controlled case series study

    Ikuta K., Nakagawa S., Yamawaki C., Itohara K., Hira D., Imai S., Yonezawa A., Nakagawa T., Sakuragi M., Sato N., Uchino E., Yanagita M., Terada T.

    BMC Nephrology （BMC Nephrology)  23 （ 1 ）  2022年12月

    筆頭著者, 最終著者, 責任著者, 査読有り

    　概要を見る

    Background: Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal disorders such as peptic ulcer disease and dyspepsia. However, several studies have suggested that PPI use increases the risk of acute kidney injury (AKI). PPIs are often concomitantly used with antibiotics, such as macrolides and penicillins for Helicobacter pylori eradication. Although macrolide antibiotics are considered to have relatively low nephrotoxicity, they are well known to increase the risk of AKI due to drug-drug interactions. In this study, we aimed to investigate the association between PPI use and the development of AKI. We also evaluated the effect of concomitant use of PPIs and macrolide antibiotics on the risk of AKI. Methods: This self-controlled case series study was conducted using electronic medical records at Kyoto University Hospital. We identified patients who were prescribed at least one PPI and macrolide antibiotic between January 2014 and December 2019 and underwent blood examinations at least once a year. An adjusted incident rate ratio (aIRR) of AKI with PPI use or concomitant use macrolide antibiotics with PPIs was estimated using a conditional Poisson regression model controlled for the estimated glomerular filtration rate at the beginning of observation and use of potentially nephrotoxic antibiotics. Results: Of the 3,685 individuals who received PPIs and macrolide antibiotics, 766 patients with episodes of stage 1 or higher AKI were identified. Any stage of AKI was associated with PPI use (aIRR, 1.80 (95% confidence interval (CI) 1.60 to 2.04)). Stage 2 or higher AKI was observed in 279 cases, with an estimated aIRR of 2.01 (95% CI 1.57 to 2.58, for PPI use). For the period of concomitant use of macrolide antibiotics with PPIs compared with the period of PPIs alone, an aIRR of stage 1 or higher AKI was estimated as 0.82 (95% CI 0.60 to 1.13). Conclusions: Our findings added epidemiological information for the association between PPI use and an increased risk of stage 1 or higher AKI. However, we did not detect an association between the concomitant use of macrolide antibiotics and an increased risk of AKI in PPI users.

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総説・解説等 【 表示 ／ 非表示 】

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競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 抗体医薬品のバイオトランスフォーメーションの実態解明

    2023年04月
    -
    2027年03月

    科学研究費助成事業, 米澤 淳, 基盤研究(B), 未設定

  • 抗体医薬品に対する抗薬物抗体の実態解明と臨床疫学解析

    2019年04月
    -
    2023年03月

    科学研究費助成事業, 米澤 淳, 中川 俊作, 橋本 求, 基盤研究(B), 未設定

    　研究概要を見る

    バイオ医薬品はヒトの体内で免疫原性を持つことから、抗体医薬品に対する抗体（抗薬物抗体）が出現し、極端な薬効低下が引き起こす。しかし、抗薬物抗体の実態や出現要因に関する情報は不足する。それは、適切な臨床サンプルと測定技術に基づく研究成果が無いことにも起因する。本研究では、京大病院のリウマチ患者を対象としたKURAMAコホートを用い、革新的な測定技術を活用して、抗薬物抗体の実態解明を目指す。さらに、抗薬物抗体出現要因や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。本研究成果は、抗体医薬品使用における免疫原性の回避法の確立や個別化医療の実現に有益な、基礎的情報を提供する。
    2021年度は、京都大学医学部附属病院リウマチセンターKURAMAコホートとして登録されている311例のインフリキシマブが投与された関節リウマチ患者のうち、データが揃う41例について、バイオマーカーの解析を実施した。インフリキシマブは質量分析系で、抗薬物抗体とサイトカインはMeso Scale Discovery社の QuickPlex SQ120を用いて測定した。抗薬物抗体9例において血中濃度低下と判定され、DAS28-ESRで判定した臨床効果の減弱が確認された。他方、4例で抗薬物抗体の陽性が検出されたが、臨床効果との相関は認められなかった。さらに、前向きの治療効果継続の予測についても、IL6と組み合わせて血中濃度測定の有用性が示唆された。
    また、質量分析を用いた解析の結果、エタネルセプトで体内での、N末端2アミノ酸切断（バイオトランスフォーメーション）が明らかとなった。詳細な解析の結果、DPP4の関与が明らかとなった。効果との相関や他の抗体医薬品におけるバイオトランスフォーメーションならびに抗薬物抗体の反応性を今後検討予定である。抗体医薬品が生体内で構造変化を受けることは、ほとんど報告のない新しい現象で、バイオ医薬品の体内動態研究に新しい概念を提唱するものと考える。
    抗薬物モノクローナル抗体の作製が遅れているが、臨床効果との相関解析やバイオトランスフォーメーションの発見は想定より進んでいる。
    昨年度までに収集したデータの解析を進め、バイオマーカーの同定とバイオトランスフォーメーションの実態解明を進める計画である。

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担当授業科目 【 表示 ／ 非表示 】

  • 課題研究（統合臨床薬理学）

    2023年度

  • 課題研究（臨床薬物動態学）

    2023年度

  • 演習（統合臨床薬理学）

    2023年度

  • 卒業研究１（薬学科）

    2023年度

  • 実務実習事前学習（実習）

    2023年度

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