Details of a Researcher - Igarashi, Yuki

External validation of a flowchart related to achieving the target area under the concentration-time curve for vancomycin: A retrospective multicenter study.

Tomoyuki Ishigo, Ayako Suzuki, Yuta Ibe, Satoshi Fujii, Masahide Fukudo, Hiroaki Yoshida, Hiroaki Tanaka, Hisato Fujihara, Fumihiro Yamaguchi, Fumiya Ebihara, Takumi Maruyama, Yusuke Yagi, Yukihiro Hamada, Masaru Samura, Fumio Nagumo, Toshiaki Komatsu, Atsushi Tomizawa, Akitoshi Takuma, Hiroaki Chiba, Yoshifumi Nishi, Yuki Igarashi, Yuki Enoki, Kazuaki Matsumoto

Journal of Infection and Chemotherapy 31 ( 5 ) 2025.05

Accepted, ISSN 1341321X

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During therapeutic drug monitoring (TDM) for vancomycin (VCM), the area under the concentration-time curve (AUC) is important for balancing efficacy versus toxicity. In a previous study, we developed a decision tree (DT) model to achieve the target AUC during TDM over the follow-up period (AUCfollow-up). This study aimed to validate the DT model for achieving the target AUCfollow-up. Patients who received VCM for at least 72 h and had an initial TDM within four doses between January 2023 and December 2023 were analyzed. The AUC of the initial TDM was calculated over 2-point (peak/trough) concentrations via Bayesian estimation. The target AUCfollow-up was defined as 400–600 μg h/mL. Among 188 patients (median age [interquartile range], 66 [56, 79] years; 50 % female), the target AUCfollow-up was achieved in 70 % (132/188). When the predicted AUC was 400–600 μg h/mL, 84 % (102/121) achieved the target AUCfollow-up. In a 12 h dosing interval subgroup, 86 % (88/102) achieved the target AUCfollow-up. Conversely, when the predicted AUC was <400 or >600 μg h/mL, the proportion who achieved the target AUCfollow-up dropped to 44 % (30/67). Only 30 % (3/10) of those with creatinine clearance rates of >130 mL/min/1.73 m2 achieved the target. The area under the receiver operating characteristics curve was 0.74, and the R2 value was 0.15. Our findings confirmed the external validity of the DT model and supported its use for optimizing VCM dosing. Overall, the DT model offers a reliable framework for achieving target AUC values during follow-up for TDM, aiding safe and effective treatment.
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Influence factors of metronidazole-related CNS disorders: an analysis of the Japan adverse drug event report and FDA adverse event reporting system

Takada K., Enoki Y., Samura M., Igarashi Y., Taguchi K., Tanikawa K., Matsumoto K.

Expert Opinion on Drug Safety 2025.04

Research paper (scientific journal), Accepted, ISSN 14740338

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Background: Metronidazole (MNZ) can be administered for various infections. The impact of comorbidities/concomitant drugs on MNZ-induced central nervous system (CNS) disorders remains unclear. Research design and methods: We assessed the risk of metronidazole-related CNS disorders using the Japan Adverse Drug Event Report (JADER, May 2023) and the US Food and Drug Administration Adverse Event Reporting System (FAERS, Q1 2023), excluding comorbidities/concomitant drugs. Clonazepam and diazepam were evaluated as potential prophylactics based on the efficacy of benzodiazepines for MNZ-related CNS disorders. Reporting odds ratios (ROR) and 95% confidence intervals (CI) were calculated. Additionally, sensitivity analysis by sex and age was conducted. Results: The ROR (95% CI) of CNS disorders associated with MNZ in JADER and FAERS were 3.16 (2.69–3.72) and 1.69 (1.64–1.73), respectively. MNZ was significantly related to CNS disorders after excluding comorbidities (brain/spinal cord or liver abscesses) and concomitant drugs (glucocorticoids, antiepileptic, antiparkinson, and schizophrenia drugs). In sensitivity analysis, MNZ was significantly related to CNS disorders, despite sex and age. The ROR in the concomitant with clonazepam (CZP) was 0.70 (0.53–0.92) in FAERS. Conclusion: MNZ may be associated with CNS disorders, even if comorbidities/concomitant drugs that are potential risk factors for CNS disorders are excluded. Additionally, CZP may suppress CNS disorders.
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Development and validation of a population pharmacokinetic model of vancomycin for patients of advanced age

Takada K., Samura M., Igarashi Y., Suzuki A., Ishigo T., Fujii S., Ibe Y., Yoshida H., Tanaka H., Ebihara F., Maruyama T., Hamada Y., Komatsu T., Tomizawa A., Takuma A., Chiba H., Yagi Y., Nishi Y., Enoki Y., Taguchi K., Tanikawa K., Kunishima H., Matsumoto K.

Journal of Pharmaceutical Health Care and Sciences 11 ( 1 ) 2025.03

Accepted

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Background: Population pharmacokinetic (PPK) models of vancomycin (VCM) commonly use creatinine clearance (CLcr) as a covariate for clearance (CL). However, relying on CLcr in patients of advanced age may lead to inaccuracies in estimating VCM clearance. Therefore, this study aimed to develop and validate a new PPK model specifically for patients aged 75 years and older. Methods: PPK analysis was performed based on the blood concentrations of VCM (n = 159 patients). The predictive performance of the developed model was compared with that of previous models using mean absolute error (MAE) and mean squared error (MSE) for another dataset. Results: The PPK analysis optimized a two-compartment model using CLcr and the Alb levels as covariates at the central compartment of VCM clearance. The final model was as follows: CL (L/h) = 1.96 × (CLcr/3.09) 0.63 × (Serum albumin (Alb) /2.3) 0.22 × exponential (0.11). Clearance between the central and peripheral compartments (L/h) = 4.86. Central compartment volume of distribution (L) = 31.78. Peripheral compartment volume of distribution (L) = 53.64. The validation study revealed that compared with those of previous models (ranging from 0.67 to 0.79 L/h and from 0.81 to 1.11 (L/h)2, respectively), the final model demonstrated the smallest MAE of 0.60 L/h and MSE of 0.65 (L/h)2 for patients of advanced age with serum creatinine levels of < 0.6 mg/dL. Conclusion: The PPK model of VCM for patients of advanced age was optimized by adding the Alb levels and CLcr as covariates for CL. The predictive accuracy of the PPK model for patients with an SCr of < 0.6 mg/dL tended to be higher than those of previous models based just on CLcr. Thus, dosage is suggested to be adjusted based on CLcr and Alb levels for patients with an SCr of < 0.6 mg/dL.
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SARS-CoV-2 mRNA vaccine-related myocarditis and pericarditis: An analysis of the Japanese Adverse Drug Event Report database.

Keisuke Takada, Kazuaki Taguchi, Masaru Samura, Yuki Igarashi, Yuko Okamoto, Yuki Enoki, Koji Tanikawa, Kazuaki Matsumoto

Journal of Infection and Chemotherapy 31 ( 1 ) 2025.01

Accepted, ISSN 1341321X

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Background: The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines and myocarditis/pericarditis in the Japanese population has not been systematically investigated. This study was aimed at clarifying the association between SARS-CoV-2 mRNA vaccines (BNT162b2 and mRNA-1273) and myocarditis/pericarditis as well as influencing factors by using the Japanese Adverse Drug Event Report database. Methods: Reporting odds ratios (RORs) and 95 % confidence intervals (95 % CIs) for the association between the vaccines and myocarditis/pericarditis were calculated using data from the database (April 2004–December 2023). Age, sex, onset time, and outcomes in symptomatic patients were evaluated. Results: The total number of reports was 880,999 (myocarditis: 1846; pericarditis: 761). The adverse events associated with the vaccines included myocarditis (919 cases) and pericarditis (321 cases), with the ROR [95 % CIs] being significant for both (myocarditis: 30.51 [27.82–33.45], pericarditis: 21.99 [19.03–25.40]). Furthermore, the ROR [95 % CIs] of BNT162b2 and mRNA-1273 were 15.64 [14.15–17.28] and 54.23 [48.13–61.10], respectively, for myocarditis, and 15.78 [13.52–18.42] and 27.03 [21.58–33.87], respectively, for pericarditis. Furthermore, most cases were ≤30 years or male. The period from vaccination to onset was ≤8 days, corresponding to early failure type based on analysis using the Weibull distribution. Outcomes were recovery or remission for most cases; however, they were severe or caused death in some cases. Conclusion: In the Japanese population, SARS-CoV-2 mRNA vaccination was significantly associated with the onset of myocarditis/pericarditis. The influencing factors included age of ≤30 years and male. Furthermore, although most adverse events occurred early after vaccination, overall outcomes were good.
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Simulated achievement rate of β-lactams/nacubactam treatment in humans using instantaneous MIC-based PK/PD analysis.

Yuki Igarashi, Kazuaki Taguchi, Yuki Enoki, Victor Tuan Giam Chuang, Kazuaki Matsumoto

Journal of Antimicrobial Chemotherapy 80 ( 2 ) 547 - 553 2024.12

Lead author, Accepted, ISSN 03057453

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Background: Nacubactam (NAC), a new diazabicyclooctane β-lactamase inhibitor, is being developed for use together with aztreonam (AZT) and cefepime (CFPM). However, the effective clinical dosages of AZT/NAC and CFPM/NAC have not yet been established. We have previously shown that free time above instantaneous MIC (fT > MICi) is a valuable pharmacokinetic (PK)/pharmacodynamic parameter for β-lactam (BL)/NAC in a mouse thigh infection model. Objectives: This study simulated the fT > MICi (%) for AZT/NAC and CFPM/NAC against carbapenemase-producing Enterobacterales (CPE) with different MIC in humans to estimate the clinical efficacy at practically achievable combination doses of AZT/NAC and CFPM/NAC. Methods: Using previously reported PK parameters of each drug in humans and chequerboard MIC data, we calculated the fT > MICi (%) for AZT/NAC and CFPM/NAC in 10 000 simulated patients to predict the percentages of target attainment of bacteriostatic and bactericidal efficacies at various combined doses. Results: The results predicted that both BL/NAC combinations could achieve 100% 2 log10-kill against CPE strains at the lowest combination dose (0.5 g/0.5 g q8h). Additionally, in MIC studies examining BLs/NAC at a 1:1 ratio, the dosage regimen for strains with MICcomb ≤ 1 mg/L was expected to offer 100% bactericidal efficacy (2 log10-kill) at 0.5 g/0.5 g q8h or higher doses. For strains with 1 mg/L < MICcomb ≤ 16 mg/L, BLs/NAC at a 2 g/2 g q8h was predicted to produce bactericidal efficacy (1 log10-kill). At MICcomb = 32 mg/L, some bacteriostatic effect was expected at high BL doses. Conclusions: AZT/NAC and CFPM/NAC are bactericidal against CPE at practically achievable dosages.
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Presentations 【 Display / hide 】

肺炎球菌感染症に対する13価、15価の肺炎球菌ワクチン単剤接種及び23価肺炎球菌ワクチンとの併用接種の有効性並びに安全性比較：システマティックレビュー&メタ解析

坪内愛佑、松本ゆうり、三原貴之、岡本侑子、池上眞太郎、高橋実秀、中林花音、西本直人、水上雄貴、村石琢真、五十嵐裕貴、榎木裕紀、田口和明、松元一明

第９回日本老年薬学会 (千葉県) ,

2025.06
,
Oral presentation (general)
Mycobacterium avium complexに対するβラクタム系薬2剤併用のin vitro有効性評価

吉川万衣子、西村知泰、三澤可奈、島村莉奈、鈴木健太、五十嵐裕貴、榎木裕紀、長谷川直樹、南宮湖、松元一明

第8回フレッシャーズカンファランス (京都府) ,

2025.06
,
Oral presentation (general)
診療情報データベースを用いたDays of Antibiotic Spectrum Coverage(DASC)に基づく診療科および診療体制に着目した抗菌薬使用量調査

中林花音, 髙田啓介, 今井俊吾, 佐村優, 鈴木絢子, 岡本侑子, 五十嵐裕貴, 榎木裕紀, 堀里子, 松元一明

第8回フレッシャーズカンファランス (京都府) ,

2025.06
,
Oral presentation (general)
抗菌薬投与が引き起こすMycobacterium abscessus の細胞壁脂質とコロニー形態変化

島村莉奈、西村知泰、吉川万衣子、三澤可奈、矢野大和、榎木裕紀、五十嵐裕貴、長谷川直樹、南宮湖、松元一明

第8回フレッシャーズカンファランス (京都府) ,

2025.06
,
Oral presentation (general)
β-ラクタム薬/β-ラクタマーゼ阻害薬の併用療法における in vivo pharmacokinetics/pharmacodynamics評価方法の構築

五十嵐裕貴

第73回日本化学療法学会総会 (神奈川県) ,

2025.05
,
Poster presentation

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Awards 【 Display / hide 】

第8回フレッシャーズ・カンファランス優秀演題発表賞

島村莉奈,西村知泰,吉川万衣子,三澤可奈,矢野大和,榎木裕紀,五十嵐裕貴,長谷川直樹,南宮湖,松元一明, 2025.06, 抗菌薬投与が引き起こすMycobacterium abscessusの細胞壁脂質とコロニー形態変化

Type of Award： Award from Japanese society, conference, symposium, etc.
日本化学療法学会Young Challenger Award（YCA）2025

五十嵐裕貴, 2025.05, 日本化学療法学会, β-ラクタム薬/β-ラクタマーゼ阻害薬の併用療法におけるin vivo pharmacokinetics/pharmacodynamics評価方法の構築

Type of Award： Award from Japanese society, conference, symposium, etc.
第34回日本医療薬学会年会Postdoctoral award

五十嵐裕貴, 2024.11, 日本医療薬学会, β-ラクタム薬/β-ラクタマーゼ阻害薬の併用療法におけるin vivo pharmacokinetics/pharmacodynamics評価方法の構築

Type of Award： Award from Japanese society, conference, symposium, etc.
2023年度KP会星野尚美記念薬学研究・活動奨励賞研究論文部門

五十嵐裕貴, 2024, Development of an optimized and practical pharmacokinetics/pharmacodynamics analysis method for aztreonam/nacubactam against carbapenemase-producing K. pneumoniae

Type of Award： Other
Sato Pharmaceutical Research Encouragement Award

五十嵐裕貴, 2020, 佐藤製薬株式会社, PK/PD理論に基づくCefditorenの適正使用を目指したマウスにおける薬物動態研究

Type of Award： Other