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Papers - Suzuki, Sayo

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A simulated interprofessional team conference using cross-training in interprofessional education: A qualitative content analysis.

Etsuko Tomizaki, Junji Haruta, Takashi Horiguchi, Tomoko Arahata, Rika Fukui, Shunsuke Uno, Takayuki Ando, Tetsuhiro Yoshino, Satoko Ishikawa, Sayo Suzuki, Katsunori Yamaura, Toshiaki Monkawa.

Advances in Medical Education and Practice. 16 583 - 594 2025.04

Research paper (scientific journal), Joint Work, Accepted

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Evaluation of Medication Adherence Among Prevalent Users in Hypertension, Dyslipidemia, and Diabetes Using Health Insurance Claims: A Population-Based Cohort Study in Japan.

Matsumoto M., Harada S., Ikuta H., Iida M., Kato S., Sata M., Shibuki T., Ishibashi Y., Miyagawa N., Hisamatsu M., Hirata A., Kuwabara K., Takeuchi A., Sugiyama D., Suzuki S., Nakamura T., Okamura T., Takebayashi T.

Pharmacoepidemiology and Drug Safety 33 ( 8 ) e5855 2024.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 10538569

Purpose: Hypertension (HT), dyslipidemia (DL), and diabetes mellitus (DM) are major risk factors for cardiovascular diseases. Despite the wide availability of medications to reduce this risk, poor adherence to medications remains an issue. The aim of this study is to evaluate medication adherence of prevalent users in these disease medications (HT, DL, DM) using claims data. Factors associated with non-adherence were also examined. Methods: Of 7538 participants of the Tsuruoka Metabolomics Cohort Study, 3693 (HT: 2702, DL: 2112, DM: 661) were identified as prevalent users of these disease medications. Information on lifestyle was collected through a questionnaire. Adherence was assessed by a proportion of days covered (PDC) and participants with PDC ≥0.8 were defined as adherent. Predictors of non-adherence were determined by performing multivariable logistic regression. Results: Medication adherence differed by treatment status. Among those without comorbidities, those with HT-only showed the highest adherence (90.2%), followed by those with DM-only (81.2%) and those with DL-only (80.8%). Factors associated with non-adherence in each medication group were skipping breakfast and poor understanding of medications among those with HT medications, females, having comorbidities, having a history of heart disease, and drinking habit among those with DL medications, and good sleep quality and skipping breakfast among those with DM medications. Conclusion: While participants showed high medication adherence, differences were observed across medication groups. The identified predictors of non-adherence could help target those in need of adherence support.

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Considering Medical Professionalism from the Standpoint of Pharmacy Education

Suzuki Sayo

YAKUGAKU ZASSHI (The Pharmaceutical Society of Japan) 144 ( 6 ) 615 - 624 2024.06

Research paper (scientific journal), Lead author, Last author, Corresponding author, Accepted, ISSN 0031-6903

Worldwide interest in teaching medical professionalism has increased drastically over the past two decades and is recognized as an important core competency. It is also essential in pharmacy education. However, there is no single definition of medical professionalism owing to its multifaceted nature, leading to difficulty in understanding it. The foundational concept of professionalism are the social contract and accountability, which describe the relationship between the profession and the society which it serves. Profession must understand expectations from the society, which is trustworthy, assures competence, and devoted to the public good for the contract based on their mutual trust. In “teaching,” three basic educational actions (“setting expectations,” “providing experiences,” and “evaluating outcomes”) are required. There are two learning goals of professionalism education: the minimum goal of not doing unprofessional acts and the aspirational goal of pursuing a higher level of interiorized professionalism which leads to the professional identity formation. The true professionals are “reflective practitioners,” who have the ability to manage ambiguous problems using their interiorized professionalism in complicated situations. Therefore, reflection is one of the central concepts of professionalism education. The Professionalism Mini-Evaluation Exercise (P-MEX), an observational tool to evaluate medical professionalism, has some favorable aspects; the Japanese version is available and is a guide to specific actions for professionalism through its items, although some cautions must be exercised when using it. Considering that teaching professionalism includes not only formal but informal and hidden curricula, all of the staff in the educational environments should consider professionalism education by understanding professionalism.

Outcomes that pharmacy education should aim for, as considered with specialists in each field

Takeda Kayoko, Sayo Suzuki

Japanese Journal of Pharmaceutical Education (Japan Society for Pharmaceutical Education) 8 ( 0 ) n/a 2024.03

Research paper (scientific journal), Last author, ISSN 24324124

In 2024, a new model core curriculum for pharmacy education based on needs from society will be implemented. Many universities are focused on how to develop the qualities and competencies required for pharmacists in undergraduate education. However, the final goal of outcome in undergraduate education should be the spread to society and the world of the high level of expertise that pharmacy graduates should truly aspire to or demonstrate their competency to contribute to society. In fact, recently, International Pharmaceutical Federation indicates that “Making an impact on society” that is one of the pillars of qualities of pharmacy education is the final proof of it. And based on this, it should be necessary to reflect on undergraduate education and improve and review education. In this symposium, lecturers who have already contributed to society, demonstrated a high level of expertise and made an impact on the world gave lectures and discussed pharmacy education across fields. In particular, the lecturers gave an overview of current cutting-edge research from areas C, D, E and F of the current model core curriculum, from drug discovery to clinical practice. This was followed by a discussion on the future prospects of those areas and the points to be improved and expectations for future pharmacy education as perceived by the lecturers.

Pharmacokinetics/pharmacodynamics analysis and establishment of optimal dosing regimens using unbound cefmetazole concentration for patients infected with Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E).

Takaya Namiki, Yuta Yokoyama, Hideki Hashi, Rentaro Oda, Aya Jibiki, Hitoshi Kawazoe, Kazuaki Matsumoto, Sayo Suzuki, Tomonori Nakamura.

Pharmacotherapy. (Pharmacotherapy) 44 ( 2 ) 149 - 162 2024.02

Research paper (scientific journal), Joint Work, Accepted, ISSN 0277-0008

Study Objective: Establish methods for measuring cefmetazole (CMZ) concentrations conduct a pharmacokinetic/pharmacodynamic (PK/PD) analysis using unbound CMZ concentrations for extended-spectrum β-lactamase producing enterobacterales (ESBL-E) and investigate optimal dosing regimens for not undergoing hemodialysis (non-HD) and undergoing hemodialysis (HD) patients. Design: Prospective observational study. Patients: Included patients treated with CMZ who provided written informed consent and were admitted to the Tokyo Bay Urayasu Ichikawa Medical Center between August 2021 and July 2022. Measurements: Total and Unbound CMZ concentration was measured by high-performance liquid chromatography (HPLC) with solid-phase extraction and ultrafiltration. Setting: Determining the CMZ dosing regimen involved modified creatinine clearance (CLCR) with measured body weight (BW) using the Cockcroft–Gault equation. For non-HD patients, blood samples were collected during at least three points. For patients undergoing HD, 1 g was administered via intravenous infusion, or rapid intravenous injection after HD, or 30 min before the end of HD. Blood samples were collected before HD (pre-HD), and 1 and 3 h after starting HD and post-HD. All blood samples were collected at steady-state. Patient information was collected from electronic medical records. An unbound PK model was constructed for the non-HD patients. A nomogram was constructed using Monte Carlo simulations with a 90% probability of target attainment at 70% free time above the minimum inhibitory concentration (MIC). For the HD patients, a nomogram was used to determine the optimal dosing regimen for each HD schedule. Main Results: CMZ measurement methods were established. A model analysis of unbound PK in 37 non-HD patients incorporated creatinine clearance (CLCR) using the Cockcroft–Gault equation, albumin (ALB) for clearance and body weight (BW) for the volume of distribution. In Monte Carlo simulations, nomograms corresponding to the MIC (known and unknown) were generated for each covariate. Using the nomogram, non-HD patients with an ESBL-E MIC of 8 mg/L, a BW of 60 kg, an ALB of 25 g/L, and a CLCR of 60 mL/min required administration of 2 g every 6 h (1- and 3-h infusions). Unbound PK model parameters were calculated for 7 HD patients, and the optimal dosing regimens following PK/PD were determined for each HD schedule. In HD patients, the regimen after and during HD was established using a treatment that was effective up to an ESBL-E MIC of 4 mg/L. Conclusions: The nomogram for CMZ regimens established by PK/PD analysis of measured CMZ concentrations enables optimal CMZ dosing for ESBL-E-infected patients.

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Drug repositioning study on the antiemetic efficacy of anamorelin for cisplatin-induced nausea and vomiting in rats.

Nishino Haruto, Kawazoe Hitoshi, Sekiguchi Mayu, Jibiki Aya, Yokoyama Yuta, Suzuki Sayo, Nakamura Tomonori.

BPB Reports (The Pharmaceutical Society of Japan) 7 ( 1 ) 1 - 6 2024.01

Research paper (scientific journal), Joint Work, Accepted

Objective: Platinum- and anthracycline-based chemotherapy regimens cause nausea and vomiting in clinical practice, resulting in the deterioration of patients’ QoL, discontinuation of chemotherapy, and reduced therapeutic outcomes. Using pica behavior as an indicator, we aimed to clarify whether anamorelin, an orally active ghrelin receptor agonist, exerts antiemetic effects against cisplatin-induced nausea and vomiting in rats. Materials and Methods: Sprague–Dawley rats were treated with cisplatin (5 mg/kg, i.p.), three-drug or four-drug antiemetics (granisetron [0.3 mg/kg, p.o.], dexamethasone [1.5 mg/kg, p.o.], fosaprepitant [12.5 mg/kg, i.p.], with or without anamorelin [30 mg/kg, p.o.]). Data on kaolin intake, normal food intake, and spontaneous motor activity (SMA) were recorded 1 d before and 5 d after cisplatin administration. Body weight (BW) was measured daily, and the percentage change in BW from baseline was calculated. Results: At the primary endpoint, kaolin intake was significantly higher in the cisplatin-only group than in the pretreatment and vehicle groups (p < 0.05). Additionally, kaolin food intake was not significantly low in cisplatin-treated mice treated with three-drug antiemetics with or without anamorelin. At the secondary endpoints, normal food intake, SMA, and percentage change in BW were significantly lower in the cisplatin-only group than in the vehicle group. Conclusion: Our findings suggest that the prophylactic administration of standard three-drug antiemetics, besides anamorelin, may not improve cisplatin-induced nausea and vomiting. Further studies using methods suitable for evaluating anamorelin levels are required.

Patient prognosis and prediction model for taking Kampo formulas in dysmenorrhea: An observational study.

Maeda-Minami, Ayako, Kawamoto Ayako, Yoshino Tetsuhiro, Yokoyama Yuta, Suzuki Sayo , Horiba Yuko, Nakamura Tomonor, Mimura Masaru, Watanabe Kenji.

Medicine (Medicine (United States)) 102 ( 48 ) e36191 2023.12

Research paper (scientific journal), Accepted, ISSN 0025-7974

Two representative Kampo formulas, keishibukuryogan and tokishakuyakusan, are frequently prescribed for patients with dysmenorrhea. We previously constructed a model that could predict which of these 2 formulas was most suitable, which is based on 4 subjective symptoms and 3 objective signs. To evaluate the prognosis of patients with dysmenorrhea using the established prediction model and assess the treatment outcomes between those treated in accordance with the prediction model and those who received various other treatments. In this retrospective, observational study, we included patients with menstrual pain who visited the Kampo Clinic at the Keio University Hospital for the first time between October 2014 and December 2020. These patients were monitored over a 90-day follow-up period. Participants were categorized into 2 groups: model-accordance and various-options. The progression of visual analogue scale (VAS) values was evaluated by determining the slopes from regression analysis between these 2 groups, with changes corroborated by the medical records. The study comprised 57 patients: 37 in the model-accordance group and 20 in the various-options group. Notably, the various-options group reported a significantly higher number of subjective symptoms (P = .03). The VAS value showed a decline, as indicated by the negative slope value of the regression line, across both groups - irrespective of their classification. There were no significant differences in the occurrence of adverse events between the 2 groups. The prognosis of patients with dysmenorrhea and the incidence of adverse events remained consistent, regardless of whether the treatment approach was in accordance with the prediction model or varied. Further studies are warranted to assess the prognosis when Kampo formulas are chosen based on the prediction model in the various-options population.

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優れた研究能力と高い専門性を活用し患者アウトカムを改善する！

山口浩明, 鈴木小夜

The Annual Meeting of Japanese Society of Pharmaceutical Health Care and Sciences (Japanese Society of Pharmaceutical Health Care and Sciences) 33 ( 0 ) 50 - 55 2023.11

Research paper (international conference proceedings), Accepted

What Factors Improve the Evaluation of Achievement at the End of Pharmacy Practice Experiences?

Ishikawa H, Kawazoe H, Iwata H, Nakamura Y, Jibiki A, Yokoyama Y, Kobayashi N, Suzuki S, Yamaura K, Nakamura T.

Japanese Journal of Pharmaceutical Health Care and Sciences (Japanese Society of Pharmaceutical Health Care and Sciences) 49 ( 4 ) 173 - 182 2023.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 1346-342X

In the pharmacy practice experience (PPE) component of the pharmaceutical education model core curriculum, factors by which achievement can best be evaluated in rubric format have not been empirically determined. In this study, multivariate analysis was conducted based on characteristic information obtained from PPEs.Data were analyzed from a total of 146 fifth-year students of Keio University Faculty of Pharmacy who completed PPEs in 2021. Using “Learning Results Prior to PPE”, “Presence / Absence of Role Model in PPE”, “Number of Experience Areas focused on Representative Eight Diseases”, and “Number of People who were Provided Medication Instruction” as the explanatory variables, and “Number of Mentor-provided Performance Evaluations with Scores ≥3” and “Sum of Mentor-provided Performance Evaluation Scores” as the objective variables, multiple regression analysis was performed. For “Number of Mentor-provided Performance Evaluations with Scores ≥3” predictions in training at a pharmacy, training at a hospital, or both, the respective probability values were <0.001, 0.189, and 0.012. For “Sum of Mentor-provided Performance Evaluation Scores”, the respective probability values were 0.005, 0.046, and 0.048. The effect of “Number of Experience Areas focused on Representative Eight Diseases” on each objective variable was consistently large.Multivariate analysis using PPE-relevant collected information identified factors that improve the evaluation of achievement at the end of a PPE.

Ingenol mebutate inhibits the growth of pancreatic cancer cells in vitro via STING with an efficacy comparable to that of clinically used anticancer agents.

Kikuyama F, Suzuki S, Jibiki A, Yokoyama Y, Kawazoe H, Kitanaka S, Nakamura T

Journal of natural medicines (Journal of Natural Medicines) 77 ( 2 ) 343 - 351 2023.01

Research paper (scientific journal), Joint Work, Corresponding author, Accepted, ISSN 1340-3443

Pancreatic cancer is associated with a poor prognosis; thus, there is an urgent need to develop new and effective treatments. Ingenol mebutate (IM), which is isolated from the latex of Euphorbia peplus, was recently shown to be effective against pancreatic cancer cell lines; however, its mechanism of action has not been fully elucidated. In this study, we focused on the less drug-sensitive pancreatic cancer cell line Panc-1 and compared IM to commercially available anticancer drugs using cell survival assays. In addition, we aimed to identify novel biomolecules that may be involved in the mechanism of action of IM using RNA sequencing, western blotting, and inhibition assays. The IC50 values after 72 h of exposure to IM and SN-38, drugs to which the Panc-1 cells are most sensitive among the tested anticancer agents, were 43.1 ± 16.8 nM and 165 ± 37 nM, respectively. IM showed a cytostatic effect equal to or greater than that of the clinically used pancreatic cancer therapeutic drugs. RNA sequencing and protein expression analysis revealed that expression of stimulator of interferon genes (STING) increased at low IM concentration, whereas cell viability decreased. Co-exposure of IM and STING inhibitor, H-151, to Panc-1 or MIA PaCa-2 cell lines canceled the growth-inhibitory effects of IM alone. In conclusion, IM may have an efficacy comparable to that of existing pancreatic cancer therapeutic agents on the less drug-sensitive Panc-1 cell line and the immune-related molecule STING plays a role in the mechanism of action of IM.

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Population Pharmacokinetics, Pharmacogenomics, and Adverse Events of Osimertinib and its Two Active Metabolites, AZ5104 and AZ7550, in Japanese Patients with Advanced Non-small Cell Lung Cancer: a Prospective Observational Study.

Ishikawa E, Yokoyama Y, Chishima H, Kasai H, Kuniyoshi O, Kimura M, Hakamata J, Nakada H, Suehiro N, Nakaya N, Nakajima H, Ikemura S, Kawada I, Yasuda H, Terai H, Jibiki A, Kawazoe H, Soejima K, Muramatsu H, Suzuki S, Nakamura T

Investigational new drugs (Investigational New Drugs) 41 ( 1 ) 122 - 133 2023.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 0167-6997

Background: Potential novel strategies for adverse event (AE) management of osimertinib therapy, including therapeutic drug monitoring and the use of biomarkers, have not yet been fully investigated. This study aimed to evaluate (1) the relationship between exposure to osimertinib, especially its active metabolites (AZ5104 and AZ7550), and AEs, and (2) the relationship between germline polymorphisms and AEs. Methods: We conducted a prospective, longitudinal observational study of 53 patients with advanced non-small cell lung cancer receiving osimertinib therapy from February 2019 to April 2022. A population pharmacokinetic model was developed to estimate the area under the serum concentration–time curve from 0 to 24 h (AUC0–24) of osimertinib and its metabolites. Germline polymorphisms were analyzed using TaqMan® SNP genotyping and CycleavePCR® assays. Results: There was a significant association between the AUC0–24 of AZ7550 and grade ≥ 2 paronychia (p = 0.043) or anorexia (p = 0.011) and between that of osimertinib or AZ5104 and grade ≥ 2 diarrhea (p = 0.026 and p = 0.049, respectively). Furthermore, the AUC0–24 of AZ5104 was significantly associated with any grade ≥ 2 AEs (p = 0.046). EGFR rs2293348 and rs4947492 were associated with severe AEs (p = 0.019 and p = 0.050, respectively), and ABCG2 rs2231137 and ABCB1 rs1128503 were associated with grade ≥ 2 AEs (p = 0.008 and p = 0.038, respectively). Conclusion: Higher exposures to osimertinib, AZ5104, and AZ7550 and polymorphisms in EGFR, ABCG2, and ABCB1 were related to higher severity of AEs; therefore, monitoring these may be beneficial for osimertinib AE management.

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薬学教育が真に目指すべきコアカリの先のアウトカム

SUZUKI Sayo, TAKEDA Kayoko

Farumashia (The Pharmaceutical Society of Japan) 59 ( 2 ) 137 - 139 2023

ISSN 00148601

薬学教育モデル・コアカリキュラムには各専門領域で育成すべき資質が明示されているが，現在，それは学部教育で目指す枠組みでしかない．医療薬学フォーラム2022／第30回クリニカルファーマシーシンポジウムの「薬学教育」シンポジウムでは，各専門領域の学びの先にある真のアウトカムとも言うべき世界で活躍されている4名の先生方に，現在行っている最先端の研究・お仕事と，そのお立場から今後の薬学教育に求めることを共有いただき，今後のあるべき「薬学教育」について議論した．

基質特異性拡張型β-ラクタマーゼ産生腸内細菌目細菌感染患者に対する遊離形セフメタゾール濃度を用いたPPK/PD解析と最適投与法の構築

並木孝哉, 横山雄太, 枦秀樹, 織田錬太郎, 地引綾, 河添仁, 松元一明, 鈴木小夜, 中村智徳

Annual Scientific Meeting of The Japanese Society of Clinical Pharmacology and Therapeutics (The Japanese Society of Clinical Pharmacology and Therapeutics) 44 ( 0 ) 2-C-O12-5 2023

【目的】基質特異性拡張型β-ラクタマーゼ産生腸内細菌目細菌（ESBL-E）感染症治療において、カルバペネム系抗菌薬の代替薬としてセフメタゾール（CMZ）が注目されている。CMZは腎排泄型で蛋白結合率が高い薬剤であり、ESBL-Eに対して、fT≧MICが70％になるように投与設計することにより、有効な殺菌効果が得られると報告されている。しかし、ESBL-E感染患者に対する遊離形薬物動態（PK）パラメータを用いた最適投与法は不明である。本研究は、ESBL-E感染患者における遊離形CMZ濃度を用いた母集団薬物動態／薬力学（PPK/PD）解析を実施し、最適投与法を構築する。【方法】本研究は倫理審査委員会の承認を得て、CMZ投与患者よりインフォームドコンセントを取得した。血液サンプルはCMZ投与前、点滴終了直後、点滴終了１時間後時点等から採取した。2020年9月～2022年3月のESBL-E株のMICは、臨床検査標準協会のガイドラインに従い、微量液体希釈法より測定した。PPK解析は、PhoenixR NLMETMより、遊離形CMZ濃度を用いて、ベースモデルを構築、共変量探索、最終モデルの適格性評価を行った。組み込まれた共変量ごとに各投与法（投与量、投与間隔、点滴時間）に応じてモンテカルロシミュレーションを実施し、目標達成確率(PTA)を算出した。PTAは、10,000回のシミュレーション結果のうち70％ fT≧MICを達成する確率を示し、PTA(％)≧90％を達成する投与法を検討した。また、各菌の全株数に占める各MICの分率に、各MICでのPTAを乗じた値を総計した有効反応期待確率として算出し、投与法を検討した。【結果・考察】対象患者37人が組み込まれ、血液サンプル146検体の遊離形CMZ濃度を測定した。ESBL-E株のMIC50値及びMIC90値はそれぞれ2、4 mg/Lだった。ベースモデルは1コンパートメントモデル、混合誤差モデルが選択された。PPK解析後の遊離形CMZの最終モデル式は、CL = 16.2 × (CLCR/4.36)0.781 × (アルブミン/28)1.2 L/h、V = 47.1 × (体重/62.8)0.751 Lであった。適格性評価より、最終モデルの妥当性が示された。患者個々のCLCR、アルブミン及び体重ごとの最適投与法のノモグラムを作成し、投与量及び投与回数の増加もしくは点滴時間を延長することでPTA及び有効反応期待確率を増加することが示された。【結論】遊離形CMZ濃度を用いたPPK/PD解析を実施し、ESBL-E感染患者に対するCLCR、アルブミン及び体重ごとの最適投与法のノモグラムを構築した。

Design, Synthesis, and Monoamine Oxidase B Selective Inhibitory Activity of N-Arylated Heliamine Analogues.

Yamada Makito, Hirose Yu, Lin Bangzhong, Fujimoto Megumi, Nunomura Kazuto, Sirimangkalakitti Natchanun, Takahashi Naoyuki, Ohki, Yuuta, Sako Makoto, Murai Kenichi, Harada Kazuo, Arai Masayoshi, Suzuki Sayo, Nakamura Tomonori, Haruta Junichi, Arisawa Mitsuhiro.

ACS Medicinal Chemistry Letters 13 ( 10 ) 1582 - 1590 2022.08

Research paper (scientific journal), Joint Work, Accepted

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Simultaneous quantification of dasatinib, nilotinib, bosutinib, and ponatinib using high-performance liquid chromatography–Photodiode array detection

Yokoyama Y, Nozawa E, Morita M., Ishikawa E, Mori T, Sakurai M, Kikuchi T, Matsuki E, Yamazaki R, Kataoka K, Jibiki A., Kawazoe H, Suzuki S, Nakamura T.

Journal of Clinical Laboratory Analysis 36 ( 8 ) e24598 2022.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 08878013

Background: Dasatinib, nilotinib, and bosutinib, second-generation tyrosine kinase inhibitors (TKIs), and ponatinib, a third-generation TKI, are approved pharmaceuticals used in the treatment of chronic myeloid leukemia (CML). Although liquid chromatography-tandem mass spectrometry assays for simultaneous quantification of the four TKIs in human serum have been reported in the literature, a high-performance liquid chromatography (HPLC) assay that simultaneously quantifies these compounds has not yet been developed. This study aims to establish and validate an efficient HPLC analytical method using a photodiode array (PDA) detector for the simultaneous quantification of the four TKIs. Methods: Calibration standards were prepared by serial dilution of serum samples containing the four TKIs, followed by solid-phase extraction. The four TKIs were eluted in order within 10 min using a binary HPLC gradient system. Results: The calibration ranges were 2–500 ng/ml for dasatinib, 100–5000 ng/ml for nilotinib, and 10–500 ng/ml for bosutinib and ponatinib. Intra-day and inter-day precision and accuracy values were found to be in accordance with the U.S. Food and Drug Administration guidelines. The recovery rates were 92.9%–96.0%, 80.7%–86.1%, 91.6%–99.0%, and 86.4%–92.6% for dasatinib, nilotinib, bosutinib, and ponatinib, respectively. Conclusion: To the best of our knowledge, this is the first report of an HPLC-PDA analytical method that allows efficient simultaneous quantification of the four TKIs in the serum of patients with CML. We believe that the method developed herein can improve the efficiency of therapeutic drug monitoring in patients with CML in clinical practice.

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Development and validation of a new liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of afatinib, dacomitinib, osimertinib, and the active metabolites of osimertinib in human serum.

Ishikawa E, Yokoyama Y, Chishima H, Kuniyoshi O, Sato I, Nakaya N, Nakajima H, Kimura M, Hakamata J, Suehiro N, Nakada H, Ikemura S, Jibiki A, Kawazoe H, Muramatsu H, Suzuki S, Nakamura T

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 1199 123245 2022.05

Research paper (scientific journal), Accepted, ISSN 1570-0232

Reports on the therapeutic drug monitoring (TDM) of second- and third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer patients are limited and are required to improve the safety of EGFR-TKI therapy. Some EGFR-TKIs have active metabolites with similar or higher potency compared with the parent compounds; thus, monitoring the parent compound as well as its active metabolites is essential for truly effective TDM. In this study, we developed and validated a method that simultaneously quantifies second- and third-generation EGFR-TKIs (afatinib, dacomitinib, and osimertinib) and the active metabolites of osimertinib, AZ5104 and AZ7550, in the human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The clinical application of the method was also evaluated. The analytes were extracted from a 100 μL serum sample using a simple protein precipitation method and analyzed using LC-MS/MS. Excellent linearity of calibration curves was observed at ranges of 2.5–125.0 ng/mL for afatinib, 2.5–125.0 ng/mL for dacomitinib, 4.0–800.0 ng/mL for osimertinib, 1.0–125.0 ng/mL for AZ5104, and 2.5–125.0 ng/mL for AZ7550. The precision and accuracy were below 14.9% and within ± 14.9% of the nominal concentrations, respectively. The mean recovery was higher than 94.7% and the coefficient of variation (CV) was lower than 8.3%. The mean internal-standard normalized matrix factors ranged from 94.6 to 111.9%, and the CVs were lower than 9.7%. This analytical method met the acceptance criteria of the U.S. Food and Drug Administration guidelines. The method was also successfully applied to the analysis of 45 clinical samples; it supports the efficient and valuable analysis for TDM investigations of EGFR-TKIs.

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特集明日から使える免疫関連有害事象マネジメント　～免疫チェックポイント阻害薬の看護ケア～第Ⅳ章　免疫チェックポイント阻害薬の薬物動態を知る～くすりを知ればケアがよくなる～一般的な薬物と免疫チェックポイント阻害薬の体内動態　～薬物は体内でどのような運命をたどって効果を発揮し体内から消失していくのか～

鈴木小夜, 中村智徳

がん看護 (南江堂) 27 ( 2 ) 200 - 205 2022.02

ISSN 13420569

特集明日から使える免疫関連有害事象マネジメント　～免疫チェックポイント阻害薬の看護ケア～第Ⅳ章　免疫チェックポイント阻害薬の薬物動態を知る～くすりを知ればケアがよくなる～免疫チェックポイント阻害薬の体内動態と有効性/毒性との関係

鈴木小夜, 中村智徳

がん看護 (南江堂) 27 ( 2 ) 206 - 212 2022.02

ISSN 13420569

Prognostic Value of Baseline Medications Plus Neutrophil-to-Lymphocyte Ratio in the Effectiveness of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer: A Retrospective Study.

Ogiwara T, Kawazoe H, Egami S, Hashimoto H, Saito Y, Sakiyama N, Ohe Y, Yamaguchi M, Furukawa T, Hara A, Hiraga Y, Jibiki A, Yokoyama Y, Suzuki S, Nakamura T

Frontiers in oncology (Frontiers in Oncology) 11 770268 2021.11

Research paper (scientific journal), Joint Work, Accepted, ISSN 2234-943X

Background: Nivolumab and pembrolizumab are the standard treatments for patients with advanced non-small-cell lung cancer (NSCLC). While there are reports on several inflammatory indices and the prognosis of patients with cancer, no study has combined baseline medication with the neutrophil-to-lymphocyte ratio (NLR) to predict clinical outcomes. This study investigated the efficacy of baseline medications plus NLR to predict the effectiveness of nivolumab and pembrolizumab in a real-world clinical setting. Methods: We conducted a single-center retrospective observational study of consecutive patients with advanced NSCLC who received nivolumab or pembrolizumab as first-line, second-line, or beyond treatment between December 2015 and November 2018 at the National Cancer Center Hospital in Japan. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The drug-based prognostic score for baseline medications plus NLR was weighed based on the regression β coefficients. The multivariable Cox proportional hazard model was used to assess the association between the prognostic score-stratified groups and survival outcomes. Results: In total, 259 patients were evaluated in this study. A prognostic score calculated from the baseline medications plus NLR was used to categorize the patients into good (score 0), intermediate (scores 1–2), and poor (scores 3–6) -prognosis groups. The multivariable Cox proportional hazard model revealed a significant association between the poor-prognosis group and reduced OS. The hazard ratio of OS was 1.75 (95% confidence interval: 1.07–2.99; P = 0.031). In contrast, no association between these prognosis groups and PFS was observed. Conclusions: The findings suggest that the baseline medications with nivolumab or pembrolizumab plus NLR could lead to progressively shorter survival outcomes in patients with advanced NSCLC and could be used as a prognostic index for poor outcomes. However, to ascertain the clinical application of these findings, these concomitant medications need further validation in a large-scale multicenter study.

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Can Rubric-based Performance Evaluation Measure Students’ Performance Levels in Pharmacy Practice Experiences?: Based on the Revised Model Core Curriculum for Pharmaceutical Education.

Kawazoe Hitoshi, Suzuki Sayo, Hiraga Yui, Yokoyama Yuta, Jibiki Aya, Iwata Hiroki, Kobayashi Noriko, Fujimoto Kazuko, Nakada Hideo, Aomori Tohru, Yamaura Katsunori, Nakamura Tomonori

Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) (Japanese Society of Pharmaceutical Health Care and Sciences) 47 ( 9 ) 513 - 524 2021.09

Research paper (scientific journal), Joint Work, Corresponding author, Accepted, ISSN 1346-342X

This study aimed to clarify whether the performance levels of pharmaceutical students could be measured by a rubric-based performance evaluation, which consists of a four-point score, during pharmacy practice experiences (PPEs) at both community and hospital pharmacies on a revised model core curriculum for pharmaceutical education in Japan. We assessed the changes in performance evaluation by mentors and students during PPEs, the correlation of their total scores, and those between community pharmacies and hospitals. Data from the electronic records of fifth-year students of the Keio University Faculty of Pharmacy, who did PPEs in 2019, were retrospectively analyzed. A total of 144 students were included in this study. The median scores of performance evaluation by mentors and students in all tasks significantly increased from the commencement to the end of training in community pharmacies and hospitals (P < 0.05). Consequently, there was a significant association of total scores of performance evaluation between mentors and students in the community pharmacies (ρ = 0.755) or hospitals (ρ = 0.724). In contrast, there was a poor association of total scores of performance evaluation by mentors between community pharmacies or hospitals (ρ = 0.209) and those between community pharmacies and hospitals (ρ = 0.409). In conclusion, these findings suggest that performance evaluation by mentors and students reflects the latter’s performance level and can measure their growth in the PPEs at a community pharmacy and a hospital.

Design, synthesis, and monoamine oxidase inhibitory activity of (+)-cinchonaminone and its simplified derivatives.

Sato Yuta, Oyobe Naoko, OGAWA Takao, Suzuki Sayo, Aoyama Hiroshi, Nakamura Tomonori, Fujioka Hiromichi, Shuto Satoshi and Arisawa Mitsuhiro.

ACS Medicinal Chemistry Letters 12 ( 9 ) 1464 - 1469 2021.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 1948-5875

The absolute structure of an indole alkaloid (+)-cinchonaminone by total synthesis of both (+)-cinchonaminone and its enantiomer was determined. The main focus of the study was the enantioselective synthesis of both enantiomers of a chiral cis-3,4-disubstituted piperidine. We also evaluated monoamine oxidase (MAO) inhibitory activities of these enantiomers. Furthermore, its structurally simplified derivatives were synthesized that did not have any chiral center. Two of these derivatives showed stronger MAO inhibitory activities than that of (+)-cinchonaminone.

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Drug repositioning of antipsychotic drugs for cisplatin-induced pica behavior in mice.

Sekiguchi Mayu, Sagano Nanami, Kawzoe Hitoshi, Hiraga Yui, Jibiki Aya, Yokoyama Y,uta Suzuki Sayo, Nakamura Tomonori.

Pharmazie 76 ( 10 ) 484 - 487 2021.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 00317144

We aimed to clarify whether various antipsychotics ameliorate cisplatin-induced pica behavior in mice using a drug repositioning approach. Mice were administered cisplatin (12.5 mg/kg, i.p.) with or without olanzapine (1 mg/kg, i.p.), asenapine (4 mg/kg, i.p.), mirtazapine (5 mg/kg, i.p.) or standard three-drug antiemetics (granisetron [0.5 mg/kg, i.p.], fosaprepitant [25 mg/kg, i.p.], and dexamethasone [3 mg/kg, i.p.]). Kaolin, food, and water intake, and spontaneous motor activity on the day before and seven consecutive days after the cisplatin administration were measured using a telemetry system. At the primary endpoint, kaolin intake was significantly higher at day three in the cisplatin group than in the pre-treatment and saline groups (p < 0.05). Additionally, kaolin intake was not significantly higher in cisplatin with olanzapine, asenapine, and mirtazapine groups for seven days than in the pre-treatment group. At the secondary endpoint, cisplatin decreased the food and water intake, and spontaneous motor activity in a time-dependent manner. Three antipsychotics failed to improve the cisplatin-induced decrease in food and water intake, and spontaneous motor activity. The findings suggest that prophylactic administration of antipsychotics besides olanzapine may improve cisplatin-induced nausea and vomiting in a delayed phase and de-escalate standard 3-drug antiemetics.

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Evaluation of long-term storage stability of antimicrobial agents, antiviral agents, and sodium chloride eye drops prepared in the hospital.

Takeda Mami, Yokoyama Yuta, Watanabe Takeaki, Hiraga Yui, Jibiki Aya, Kawazoe Hitoshi, Suzuki Sayo, Kadota Keiko, Nakamura Tomonori

Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) (Japanese Society of Pharmaceutical Health Care and Sciences) 47 ( 6 ) 316 - 325 2021.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 1346-342X

It is necessary to determine the expiration date and storage methods for in-hospital preparations. However, data on the physical properties and stability of in-hospital preparations for eye drops, especially in long-term storage, are limited. Therefore, the stability of in-hospital preparations for eye drops, 0.5％ vancomycin (VCM), 0.25％ DENOSINE® (GCV), 0.1％ Funguard® (MCFG), 1％ VFEND® (VRCZ), and 5％ sodium chloride (NaCl), were evaluated for long-term storage.All eye drops were stored for 12 weeks under the following conditions: cool (4℃)/darkness, room temperature(approximately 23℃)/darkness, room temperature (approximately 24℃)/scattered light (approximately 1,500 lx), or high temperature (37℃)/darkness. The concentration of eye drops over time was measured by high-performance liquid chromatography and automated clinical chemistry analyzer, and pH, appearance, and sterility were evaluated.As a result, 0.5％ VCM eye drops can be stored for 3 weeks at room temperature when placed in a light-shielding bag or for 12 weeks at 4℃. The 0.25％ GCV, 1％ VRCZ, and 5％ NaCl eye drops can be stored for 12 weeks at 4 - 37℃. The 0.1％ MCFG eye drops can be stored for 6 weeks at 37℃, or for 12 weeks at room temperature or 4℃.The stability of in-hospital preparations for eye drops during long-term storage under varying conditions was demonstrated. Therefore, the use of in-hospital preparations for eye drops is considered to be safer and more effective.

The Effect of Minimum Medical Conditions and Community Pharmacy Practice on Outcome in Hospital Pharmaceutical Practice.

清宮啓介, 津田壮一郎, 池淵由香, 鈴木小夜, 地引綾, 岩田紘樹, 横山雄太, 河添仁, 小林典子, 藤本和子, 山浦克典, 中村智徳, 村松博, 青森達, 望月眞弓

医療薬学 46 ( 12 ) 715 - 721 2020.12

Research paper (scientific journal), Joint Work, Accepted

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Pharmacy students’ self-efficacy for pharmaceutical expertise affects successful experiences as enactive attainments in pharmacy practice experience in Japan.

Fumihiro Kikuyama, Sayo Suzuki*, Aya Jibiki, Yuta Yokoyama. Hitoshi Kawazoe, Tomonori Nakamura.

YAKUGAKU ZASSHI (The Pharmaceutical Society of Japan) 140 ( 6 ) 799 - 808 2020.06

Research paper (scientific journal), Joint Work, Corresponding author, Accepted, ISSN 00316903

Pharmacy practice experience (PPE) is essential in the six-year course of pharmaceutical education in Japan. We previously found that PPE reinforced students' self-efficacy for curriculums (SECs), leading robust acquisition and reconstruction of pharmaceutical expertise. In this study, we aimed to clarify whether students' SECs affect successful experiences as enactive attainments in PPE. We distributed survey questionnaires to the fifth-year students in Keio University in 2016-2017 before and after PPE. The students made a self-assessment of their psychological state "expect to do well" on a seven-point Likert scale for each curriculum (C1 to C18), and their successful experiences were also collected from free description type questionnaire. We could follow up 139 students. The SEC scores increased from pre-PPE to post I (p<0.001) and II terms (p<0.01). The increase in SEC scores during PPE was associated with the rate of students' successful experiences in the first-term PPE (p=0.04). The path analysis revealed the following as significant predictive factors of SECs for successful experiences: basic sciences (C1, C2, C3, C4, C5, and C6) with stand-ardizing coefficient 0.35, health and environmental sciences (C11 and C12) with 0.39, and pharmaceutical sciences (C7, C8, C9, C10, C13, and C14) with −0.51. Students in the first-term PPE tended to experience successful performance in medical professions by using their pharmaceutical expertise that they had learned. In this study, for the first time, we demonstrated that Japanese students' SECs for pharmaceutical expertise affected successful experiences, leading better outcomes of PPE.

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デキサメタゾン配合後における先発及び後発品のゲムシタビン注射剤の製剤学的安定性の評価

吉浦誠海, 河添仁, 鈴木小夜, 横山雄太, 地引綾, 中村智徳

日本臨床腫瘍薬学会雑誌 ((一社)日本臨床腫瘍薬学会) 14 1 - 7 2020.04

Research paper (scientific journal), Joint Work, Accepted

ゲムシタビン誘発性血管痛は末梢静脈投与で生じ、臨床上未解決のままとなっている。エピルビシンとオキサリプラチンにおける先行研究によれば、抗炎症作用とpH調整目的にデキサメタゾンがオプションとなる。本研究の目的は、先発及び後発品のゲムシタビンとデキサメタゾン配合の製剤学的安定性を調査することであった。我々はデキサメタゾン配合後の凍結乾燥製剤及び液体製剤のゲムシタビン先発及び後発品11品目の濃度、pH及び外観変化を生理食塩液及び5%ブドウ糖液希釈において24時間後まで評価した。濃度とpHはそれぞれ高速液体クロマトグラフィーとpHメータで測定した。配合液の濃度及びpHは生理食塩液及び5%ブドウ糖液希釈において24時間後まで変化しなかった。ゲムシタビンの液体製剤のpHは凍結乾燥製剤と比較して、生理食塩液及び5%ブドウ糖液希釈においてわずかに低かった。さらに、生理食塩液及び5%ブドウ糖液希釈において外観変化はなかった。これらの結果は、すべての先発及び後発品のゲムシタビンの製剤学的安定性はデキサメタゾン配合によって影響を受けなかった。本研究は、実臨床においてゲムシタビン誘発性血管痛の可能性を減らすために、先発及び後発品のゲムシタビンはデキサメタゾンと配合投与できることを示唆する。(著者抄録)

Educational Effect of Practical Training on Students' Robust Acquisition and Reconstruction of Expertise on Pharmaceutical Sciences They Had Learned before Practical Training

Kikuyama Fumihiro, Suzuki Sayo, Nakamura Tomonori

YAKUGAKU ZASSHI (The Pharmaceutical Society of Japan) 139 ( 9 ) 1201 - 1209 2019.09

Research paper (scientific journal), Joint Work, Corresponding author, Accepted, ISSN 0031-6903

Long-term practical training in the 6-year course of pharmaceutical education is a program for students after acquiring basic knowledge on pharmaceutical sciences and preclinical training. However, it remains unproved whether practical training affects students' robust acquisition and reconstruction of pharmaceutical expertise which they had learned before starting practical training. To address this issue, we administered survey questionnaires to 5th-year students (n=149) of Keio University in 2016 both before and after practical training. From the viewpoint of self-efficacy, psychological approach was applied to evaluate respondents' psychological state "to do well" on a 7-point Likert scale (1=disagree, 4=neither, 7=agree) for specific subjects C1-C18 (18 core units of pharmaceutical expertise in the current Model Core Curriculum for Pharmaceutical Education), mainly including basic pharmaceutical sciences, public health, clinical pharmacology and pharmacotherapy. C1-C18 total score values, which reflect the strength of certainty to acquire expertise, were significantly higher after the first term of practical training compared to before training, regardless of the pharmacy and the hospital (p<0.001), but not after the second term. Specific factors associated with increased score values for "to do well" were not extracted from other questionnaire answers concerning students' mentors or their self-learning during practical training. These results demonstrated that practical training at least partly reinforced students' feeling of "to do well", contributing to their robust acquisition and reconstruction of pharmaceutical expertise. Giving students recognition individually of their learning process themselves encourages more effective practical training toward their development of resources as a pharmacist.

The Newly Introduced Rubric-based Assessment of Students' Performance during Practical Training:: Measuring Outcome and Suggestions for Improvement Based on Students' Perspective

Suzuki Sayo, Kawazoe Hitoshi, Jibiki Aya, Yokoyama Yuta, Nakamura Tomonori

Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) (Japanese Society of Pharmaceutical Health Care and Sciences) 45 ( 4 ) 228 - 239 2019.04

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted, ISSN 1346-342X

To prepare for a new practical training scheme starting in 2019 based on a revised-model core curriculum for pharmaceutical education that incorporates outcome-based education, rubric-based assessment of student performance was implemented in practical training between May and July of 2018. The goals were to evaluate the rubric-based assessment to identify ways to improve it for appraising pharmaceutical students. All fifth-year students of the Keio University Faculty of Pharmacy in 2018 (n = 160) self-assessed their performance during practical training using evaluation sheets in a rubric form comprising three general instructional objectives with 10 task descriptions developed by the Japanese Pharmaceutical Association or Japanese Society of Hospital Pharmacists. Compared to the commencement of the training, the median evaluations in all tasks significantly increased at the completion of the practical training in the community pharmacy and the hospital settings. Survey questionnaires were administered to the students after the practical training. Customer satisfaction analysis identified two main areas for improvement of the rubric-based assessment for student growth: (1) students' lack of understanding of the rubric-based assessment in hospitals and (2) mentors' lack of understanding of it in both settings. The results suggest that rubric-based assessment is a feasible method for assessing pharmaceutical student performance during practical training. Additionally, the Faculty of Pharmacy should provide and disseminate information to students and mentors about rubric-based assessment and support mentors' efforts for student progress during practical training.

Renal dysfunction and anemia associated with long-term imatinib treatment in patients with chronic myelogenous leukemia.

Masatoshi Sakurai, Daiki Karigane, Hidenori Kasahara, Eri Matsuki, Risa Hashida, Yusuke Yamane, Ryohei Abe, Yuya Koda, Takaaki Toyama, Taku Kikuchi, Jun Kato, Takayuki Shimizu, Yuta Yokoyama,Suzuki Sayo, Tomonori Nakamura, Shinichiro Okamoto, and Takehiko Mori.

Int J Hematol. 109 ( 3 ) 292 - 298 2019.01

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

© 2019, Japanese Society of Hematology. Knowledge of the toxicity profile of long-term treatment with imatinib is limited. In the present study, we sought to evaluate renal function and hemoglobin levels during long-term imatinib treatment. Eighty-two patients with chronic myelogenous leukemia in chronic phase who had been on imatinib for over 5 years were retrospectively analyzed. The mean estimated glomerular filtration rate (eGFR) was significantly decreased over 5 years (77 ± 17 to 62 ± 14 ml/min/1.73m², P < 0.001). Higher age and lower eGFR value at initiation of imatinib were significantly associated with development of renal dysfunction by multivariate analyses. Mean hemoglobin levels also significantly decreased over the 5-year period (12.9 ± 1.7 to 12.4 ± 1.3 g/dl, P < 0.01). The rate of decrease in eGFR correlated significantly with hemoglobin levels (correlation coefficient = − 0.249, P < 0.05). Serum erythropoietin (EPO) levels did not increase in 16 patients with both renal dysfunction and anemia (median, 31.9 mIU/ml). In patients who participated in a clinical trial of imatinib discontinuation, mean eGFR (50.0 ± 6.5 to 56.0 ± 10.2 ml/min/1.73m², P < 0.05) and hemoglobin levels (12.0 ± 1.7 to 14.0 ± 1.6 g/dl, P < 0.01) improved significantly at 1 year after discontinuation. These findings suggest that long-term imatinib results in a partially reversible continuous decline in renal function and decreased hemoglobin levels.

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Macrophage-selective inhibitory effect of Kikyo-to, a Japanese traditional kampo medicine, on the viability of mouse macrophage RAW264.7 cells.

Seki Kengo, Suzuki Sayo, Mori Takehiko, Nakamura Tomonori

Proceedings for Annual Meeting of The Japanese Pharmacological Society (Japanese Pharmacological Society) 92 ( 0 ) 3 - O-13 2019

Research paper (other academic), Joint Work, Corresponding author, Accepted

Kikyo-to is a kampo medicine which is composed of Platycodi Radix (PR) and Glycyrrhizae Radix (GR), and used for Pharyngitis. As previous research in our laboratory has found the possibility that kikyo-to could influence cell viability of RAW264.7, we examined the effect of kikyo-to in detail. Decoction of both crude PR and GR, that is kikyo-to (K-D), or each crude herbal medicine, or aqueous solution of extract granule preparation of kikyo-to (K-G) were exposed to RAW264.7 mouse macrophage-derived cells, CACO-2 human colorectal cancer cells and K562 human blood cancer cells. Viability of these cells were evaluated after exposure of various dilution of these preparations.K-D decreased cell viability of RAW264.7 in a time and concentration-dependent manner and K-G also decreased cell viability of RAW264.7 in a concentration-dependent manner. In contrast, the viability of other cells did not change significantly. Decoction of GR alone decreased cell viability of RAW264.7, suggesting that components of GR may contribute to decrease in cell viability of RAW264.7, selectively. To confirm this hypothesis, further studies, functional analysis and clinical validations are needed.

Assessing pharmaceutical students' performance in practical training in a hospital:—Developing rubrics of the Keio University version and preliminary validation

Suzuki Sayo, Nakamura Tomonori

Japanese Journal of Pharmaceutical Education (Japan Society for Pharmaceutical Education) 2 ( 0 ) n/a 2018.08

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted, ISSN 2432-4124

Since 2015, in Keio University, we have developed a set of holistic rubrics for assessing students' performance in practical training in their fifth year. We have administered it on a series of trials in Keio University Hospital in 2016 and 2017 to prepare for the practical training in 2019, which is based on a "revised model core curriculum for pharmaceutical education" incorporating out-come based education. The first and second trials in 2016 identified some problems. The mentors felt burdened, and the rubrics did not work well because the descriptions of performance at each achievement level were unclear. To address these issues, first, we revised the rubrics and added examples to help mentors with the assessment. Second, the assessment frequency was decreased. Furthermore, we also organized faculty-led orientation sessions on using the rubrics not only for mentors but for all pharmacists in the facility. These efforts have resulted in the effective use of the rubrics in the subsequent 2017 trial, thus reducing the mentors' burden of using the rubrics. This is not so different from using the rating scale of Specific Behavioral Objectives (SBOs). Furthermore, to mentors, the rubrics seemed to be more proper and objective for assessing students' performance than the SBOs' rating scale.Based on these results, it is feasible to use rubrics for assessing pharmaceutical students' performance in practical training. However, effective efforts, as follows, are needed: (a) making rubrics clearer and more user-friendly, (b) familiarizing the rubrics, and (c) building unity of purpose among relevant staff.

Population pharmacokinetics of intravenous busulfan in Japanese pediatric patients with primary immunodeficiency.

Yasuyoshi Ishiwata, Masashi Nagata, Kohta Tsuge, Hiromitsu Takahashi, Sayo Suzuki, Kohsuke Imai, Masatoshi Takagi, Hirokazu Kanegane, Tomohiro Morio, Masato Yasuhara

J Clin Pharmacol 58 ( 3 ) 327 - 331 2018.02

Research paper (scientific journal), Joint Work, Accepted

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Development of a new scholastic program for medication counseling practice in preclinical training, constructed for junior students by senior students based on their experiences of on-site practice.

Suzuki Sayo

YAKUGAKU ZASSHI (日本薬学会) 137 ( 11 ) 1391 - 1408 2017.11

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted, ISSN 00316903

© 2017 The Pharmaceutical Society of Japan. Long-term practical on-site training, based on the Model Core Curriculum for Pharmaceutical Education, is a core program of the 6-year course of pharmaceutical education, introduced in Japan in 2010. In particular, medication counseling in practical training in 5th-year provides valuable opportunities for communication with real patients rather than simulated patients (SPs). However, it can also cause anxiety in 4th-year students before practical training. To address such concerns, upperclassmen (5th-and 6th-year students), who have already completed practical training, constructed and conducted a new educational program for medication counseling practice in preclinical training based on their experiences. They also developed case scenarios and played the role of patients themselves to create more realistic clinical settings. Advice from professional SPs was also provided. The 5-step program is composed of 1st counseling, 1st small group discussion (SGD) for improving counseling, 2nd revised counseling based on the 1st SGD, 2nd SGD, and development of a counseling plan and presentation. Educational effects of the program were evaluated by questionnaire survey after preclinical training in 4th-year students and after their practical training in 5th-year students. This new program, the Advanced Medication Counseling Practice, was found to be useful to reduce anxiety about communication with patients among 4th-year students (about 90%). Even after their practical training in 5th-year, they still appreciated usefulness of this program (about 80%). This program is still valued 4 years after its development. We developed the Advanced Medication Counseling Practice in preclinical training for junior students by senior students.

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電子味覚システムとヒト官能試験によるクリンダマイシンの苦味抑制飲食物の探索．

Suzuki Sayo

医療薬学 (日本医療薬学会) 43 ( 9 ) 492 - 501 2017.09

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

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The problems and improvement plans for student’s satisfaction of OTC drugs practices in pre-clinical training and clinical practice in community pharmacy

Suzuki Sayo

薬学教育 (日本薬学教育学会) 1 1 - 8 2017.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 2432-4124

薬局実務実習を終えた薬学部5年生151人と、実務実習を受け入れた延べ125薬局を対象とした。OTC薬の実習内容は、「販売」44名、「RP+見学」39名、「見学のみ」26名、「RPのみ」28名、「いずれも実施せず」13名、無回答1名であった。OTC薬実習に対して「興味」、「十分」、「満足度」を問う質問に対して「そう思う」と回答した学生は、それぞれ110名、54名、69名であった。OTC薬の種類に関する知識の必要性を感じた学生は131名、OTC薬の成分や薬理作用に関する知識の必要性を感じた学生は126名、疾患や病態の知識の必要性を感じた学生は137名であった。OTC薬実習の総合満足度を改善する因子の探索をCS分析で行い、改善度が高かった順に「学生による実際の販売(相談販売)」、「薬剤師がOTC薬を販売しているところの見学」、「OTC薬選択となる疾患や症状の基準」「学生による実際の販売(指名販売)」であった。8割以上の薬局薬剤師はOTC薬実習に関するSBOsを達成することに困難を感じていた。指導薬剤師は学生のコミュニケーションスキルの不足を感じていた。

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Suppression of antibody to infliximab by azathioprine in a patient with rheumatoid arthritis.

Aomori Tohru, Tsuchiya Ayumi, Suzuki Sayo, Jibiki Aya, Otsuka Naoko, Ishioka Eriko, Kaneko Yuko, Takeuchi Tsutomu, Nakamura Tomonori.

Die Pharmazie 72 ( 2 ) 95 - 97 2017.02

Research paper (scientific journal), Joint Work, Accepted, ISSN 00317144

© 2017, Govi-Verlag Pharmazeutischer Verlag GmbH. All rights reserved. In rheumatoid arthritis (RA) treatment, the concomitant use of methotrexate has been shown to reduce the incidence of antibodies to infliximab (ATI), on the other hand, it is unclear whether azathioprine can reduce ATI production. We enrolled a total of 10 Japanese adult patients with RA who were treated with infliximab concomitantly with methotrexate or azathioprine. Serum concentrations of infliximab and ATI of these patients were measured. The mean serum infliximab concentrations was 1.6±1.3 μg/ml in patients with methotrexate and 1.0±0.5 μg/ml in patients with azathioprine. Serum ATI concentrations were below the limit of quantitation in 4 of 5 patients in each group. The results from the present study suggest that azathioprine suppresses ATI production.

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Effect of genetic polymorphisms of azathioprine-metabolizing enzymes on response to rheumatoid arthritis treatment.

Ayumi Tsuchiya, Tohru Aomori, Mami Sakamoto, Arisa Takeuchi, Suzuki Sayo, Aya Jibiki, Naoko Otsuka, Eriko Ishioka, Yuko Kaneko, Tsutomu Takeuchi, Tomonori Nakamura.

Die Pharmazie 72 ( 1 ) 22 - 28 2017.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 00317144

© 2017, Govi-Verlag Pharmazeutischer Verlag GmbH. All rights reserved. Azathioprine (AZA) is increasingly being prescribed to rheumatoid arthritis (RA) patients. Following oral administration, AZA is converted into its active form. Inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) patients with low thiopurine (S)-methyltransferase (TPMT) activity tend to respond well to AZA therapy. In a previous study of Japanese SLE patients under low-dose AZA therapy, the group with the 94C>A mutation in inosine triphosphatase (ITPA) showed greater improvement in their disease activity index. However, it is not yet clear how genotypes relate to responsiveness to RA treatment. The genotypes ITPA 94C>A, TPMT∗3C, NUDT15 595C>T, GST-M1, GST-T1 and MRP4/ABCC4 2269G>A of Japanese patients with RA were determined. The relationship between these genotypes and response to AZA therapy was evaluated using the Disease Activity Score 28 (DAS28) and various medical data. Of the 22 patients 15 had the ITPA 94C/C genotype, 7 had the ITPA 94C/A genotype, none had the TPMT∗3C mutation, 4 had the NUDT15 595C>T mutation, 8 had the GST-M1 and T1 null genotypes and 9 had the MRP4/ABCC4 2269G>A mutation. Changes in DAS28 at 6 months after baseline were similar in both ITPA genotype groups. However, the maintenance dose of AZA was significantly lower in the C/A group than in the C/C group (0.85±0.30 mg/kg/day vs. 1.2±0.46 mg/kg/day, respectively; p = 0.043). The ITPA 94C/A group showed the same response to RA treatment as the C/C group, but at a lower dose. This demonstrates that RA patients with the ITPA 94C>A mutation are more responsive to AZA.

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Meta-analytic population pharmacokinetic analysis to evaluate the effect of renal dysfunction on imatinib clearance in Japanese subjects.

Suzuki S, Hattori Y, Takagi A, Aomori T, Kasai H, Nakamura T.

Proc Annu Meet IATDMCT 2017

Research paper (international conference proceedings), Joint Work, Lead author, Corresponding author, Accepted

Forced expression of S100A10 reduces sensitivity to oxaliplatin in colorectal cancer cells.

Suzuki S, Tanigawara Y*.

Proteome Science (BioMed Central) 12 ( 1 ) 26 2014.05

Research paper (scientific journal), Joint Work, Lead author, Accepted

Background: Individual responses to oxaliplatin (L-OHP)-based chemotherapy remain unpredictable. Our recent proteomics studies have demonstrated that intracellular protein expression levels of S100A10 are significantly correlated with the sensitivity of colorectal cancer (CRC) cells to L-OHP, but not 5-FU, suggesting that S100A10 is a candidate predictive marker for the response to L-OHP. In this study, we investigated whether S100A10 is involved in L-OHP sensitivity or not.Results: Forced expression of S100A10 in COLO-320 CRC cells significantly increased the 50% inhibitory concentration (IC50) for L-OHP (P = 0.003), but did not change that for 5-FU, indicating that S100A10 is more specific to L-OHP than 5-FU. Silencing of the S100A10 gene showed no apparent effect on sensitivity to L-OHP in HT29 cells. Silencing of the annexin A2 (a binding partner of S100A10) gene alone downregulated both annexin A2 and S100A10 protein levels, with no change in S100A10 gene expression. However, original levels of intact S100A10 protein in CRC cells positively correlated with S100A10 mRNA levels (P = 0.002, R = 0.91).Conclusions: The present results have shown that protein expression of S100A10 was associated with resistance to L-OHP, but not 5-FU, supporting the hypothesis that S100A10 expression may predict L-OHP sensitivity. Thus, our present study provides basic findings to support that S100A10 expression can be used as a predictive marker for tumor sensitivity to L-OHP. © 2014 Suzuki and Tanigawara; licensee BioMed Central Ltd.

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OTC薬実習の問題点とその改善のための提案.

剱田侑希, 門田佳子, 鈴木小夜, 青森達, 小林典子, 高木彰紀, 手塚淑人, 大谷壽一, 中村智徳*.

医療薬学誌 (日本医療薬学会) 40 ( 2 ) 117 - 123 2014.02

Research paper (scientific journal), Joint Work, Accepted

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S100A10 protein expression is associated with oxaliplatin sensitivity in human colorectal cancer cells.

Suzuki S, Yamayoshi Y, Nishimuta A, Tanigawara Y*.

Proteome Science (BioMed Central) 9 76 2011.12

Research paper (scientific journal), Joint Work, Lead author, Accepted

Background: Individual responses to oxaliplatin (L-OHP)-based chemotherapy remain unpredictable. The objective of our study was to find candidate protein markers for tumor sensitivity to L-OHP from intracellular proteins of human colorectal cancer (CRC) cell lines. We performed expression difference mapping (EDM) analysis of whole cell lysates from 11 human CRC cell lines with different sensitivities to L-OHP by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), and identified a candidate protein by liquid chromatography/mass spectrometry ion trap time-of-flight (LCMS-IT-TOF).Results: Of the qualified mass peaks obtained by EDM analysis, 41 proteins were differentially expressed in 11 human colorectal cancer cell lines. Among these proteins, the peak intensity of 11.1 kDa protein was strongly correlated with the L-OHP sensitivity (50% inhibitory concentrations) (P < 0.001, R 2 = 0.80). We identified this protein as Protein S100-A10 (S100A10) by MS/MS ion search using LCMS-IT-TOF. We verified its differential expression and the correlation between S100A10 protein expression levels in drug-untreated CRC cells and their L-OHP sensitivities by Western blot analyses. In addition, S100A10 protein expression levels were not correlated with sensitivity to 5-fluorouracil, suggesting that S100A10 is more specific to L-OHP than to 5-fluorouracil in CRC cells. S100A10 was detected in cell culture supernatant, suggesting secretion out of cells.Conclusions: By proteomic approaches including SELDI technology, we have demonstrated that intracellular S100A10 protein expression levels in drug-untreated CRC cells differ according to cell lines and are significantly correlated with sensitivity of CRC cells to L-OHP exposure. Our findings provide a new clue to searching predictive markers of the response to L-OHP, suggesting that S100A10 is expected to be one of the candidate protein markers. © 2011 Suzuki et al; licensee BioMed Central Ltd.

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患者指導用資材を活用した実践的な吸入指導実習の構築.

寺島朝子*, 前澤佳代子, 高橋麻由, 竹村知子, 小林典子, 大塚尚子, 鈴木小夜, 門田佳子, 木津純子.

日病薬誌 (日本病院薬剤師会) 47 ( 3 ) 323 - 328 2011.03

Research paper (scientific journal), Joint Work, Accepted

Protein S100A10: Expression and correlation with sensitivity to oxaliplatin in colorectal cancer cells.

Suzuki S, Nishimuta A, Tanigawara Y.

Proc Annu Meet Am Assoc Cancer Res (American Association for Cancer Research) 51 870 2010.04

Research paper (international conference proceedings), Joint Work, Lead author, Accepted

S100A10 as a potential protein biomarker for oxaliplatin sensitivity in colorectal cancer cells.

Suzuki S, Yamayoshi Y, Nishimuta A, Watanabe M, Tanigawara Y.

Proc Annu Meet Am Assoc Cancer Res (American Association for Cancer Research) 50 699 2009.04

Research paper (international conference proceedings), Joint Work, Lead author, Accepted

Protein biomarkers for predicting sensitivity to Oxaliplatin by SELDI-TOF MS screening.

Suzuki S, Yamayoshi Y., Nishimuta A., Watanabe M., Tanigawara Y.

Proceedings of the CBI Society Annual Meeting 2008 (International Synposium). (The Chemo-Bio Informatics (CBI) Society) 144 2008.10

Research paper (international conference proceedings), Joint Work, Lead author, Accepted

Discovery of blood biomarkers to predict sensitivity to CPT-11 by metabolome analysis.

Watanabe M, Arita E, Nishimuta A, Suzuki T , Yamayoshi Y, Suzuki S, Iketani O, Sagawa H, Ishikawa T, Matsuzaki T, Soga T, Tanigawara Y.

Proceedings of the CBI Society Annual Meeting 2008 (International Synposium). (The Chemo-Bio Informatics (CBI) Society) 142 2008.10

Research paper (international conference proceedings), Joint Work, Accepted

CE-TOFMS metabolome analysis of intracellular metabolite kinetics after 5-FU exposure.

Nishimuta A, Yamayoshi Y, Hirayama A, Abe J, Nagashima A, Sato H, Suzuki S, Watanabe M, Soga T, Tanigawara Y.

Proceedings of the CBI Society Annual Meeting 2008 (International Synposium). (The Chemo-Bio Informatics (CBI) Society) 143 2008.10

Research paper (international conference proceedings), Joint Work, Accepted

Metabolomic screening for blood biomarkers to predict sensitivity to CPT-11 by using CE-TOFMS.

Arita E, Watanabe M, Yamayoshi Y, Nishimuta A, Suzuki S, Iketani O, Sagawa H, Ishikawa T, Matsuzaki T, Soga T, Tanigawara Y.

Proc Annu Meet Am Assoc Cancer Res (American Association for Cancer Research) 49 1139 2008.04

Research paper (international conference proceedings), Joint Work, Accepted

Proteomic approach to discover new biomarkers that can predict Oxaliplatin sensitivity by using SELDI-TOF MS.

Suzuki S, Yamayoshi Y, Nishimuta A, Watanabe M, Tanigawara Y.

Proc Annu Meet Am Assoc Cancer Res (American Association for Cancer Research) 49 1140 2008.04

Research paper (international conference proceedings), Joint Work, Lead author, Accepted

Intracellular metabolite kinetics after 5-FU exposure by CE-TOFMS metabolome analysis.

Nishimuta A, Yamayoshi Y, Hirayama A, Abe J, Nagashima A, Sato H, Suzuki S, Watanabe M, Soga T, Tanigawara Y.

Proc Annu Meet Am Assoc Cancer Res (American Association for Cancer Research) 49 608 2008.04

Research paper (international conference proceedings), Joint Work, Accepted

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