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Affiliation |
Hospital Department of Pharmacy |
Graduating School 【 display / non-display 】
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-2002.03
Tohoku Pharmaceutical University Faculty of Pharmaceutical Science Graduated
Graduate School 【 display / non-display 】
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-2010.03
Tohoku Pharmaceutical University Graduate School, Division of Pharmaceutical Sciences Doctor's Course Completed
Campus Career 【 display / non-display 】
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2023.12-Now
Akita University Hospital Department of Pharmacy Professor
Research Areas 【 display / non-display 】
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Life Science / Clinical pharmacy
Research Achievements 【 display / non-display 】
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The prevalence of end-of-life chemotherapy and targeted therapy in Japan, assessed using a health claims database.
Masami Tsuchiya, Taku Obara, Masafumi Kikuchi, Nariyasu Mano
Cancer chemotherapy and pharmacology 2023.05 [Refereed]
Research paper (journal)
PURPOSE: This study aimed to investigate the current status of end-of-life chemotherapy and targeted therapy and explore the aggressiveness of end-of-life care in Japan using the DeSC database, a large administrative claims database. METHODS: We identified fatal cases of at least one cancer-related diagnosis between April 2015 and November 2020. Patients prescribed at least one anticancer drug were analyzed, and chemotherapy regimens were categorized based on the combination of concomitant anticancer drugs prescribed. RESULTS: Among 1,095,713 individuals enrolled in the National Health Insurance database, 7,300 deaths with cancer-related diagnosis were identified. Of these, 4,010 cases were identified in which at least one anticancer drug was prescribed, and 11.6% of 7,300 death had been prescribed anticancer drugs in their last 30 days of life. The most commonly used regimen was S-1 (tegafur, gimeracil, and oteracil potassium combination) monotherapy, followed by nivolumab monotherapy and nab-paclitaxel plus gemcitabine. Immune checkpoint inhibitor monotherapy was more likely prescribed to patients whose last chemotherapy dose was in the last 30 days of life (p = 0.0066, chi-squared test). CONCLUSIONS: This study provides insights into the current status of end-of-life chemotherapy and targeted therapy in Japan, using a large administrative claims database. The results of this study will inform future research on end-of-life chemotherapy and targeted therapy, and help develop strategies to improve the quality of life of patients with advanced cancer.
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Therapeutic Drug Monitoring of Blood Sirolimus and Tacrolimus Concentrations for Polypharmacy Management in a Lymphangioleiomyomatosis Patient Taking Two Cytochrome P450 3A Inhibitors.
Masaki Kumondai, Masafumi Kikuchi, Atsushi Mizuguchi, Nagomi Hayashi, Masahiro Ui, Takashi Hirama, Yoshinori Okada, Yu Sato, Toshihiro Sato, Masamitsu Maekawa, Nariyasu Mano
The Tohoku journal of experimental medicine 260 ( 1 ) 29 - 34 2023.03 [Refereed]
Research paper (journal)
Patients with lymphangioleiomyomatosis (LAM) and lung transplantations are treated with multiple drugs, such as tacrolimus, mycophenolate mofetil, prednisolone, and itraconazole, for long-term suppression of rejection response and prevention of infection. Additional drugs are required when lung transplant recipients develop graft complications. Therefore, managing polypharmacy is critical because of drug-drug interactions caused by various factors, including drug-metabolizing enzymes such as cytochrome P450 3A (CYP3A). The patient was a 48-year-old woman (height 144.9 cm and weight 38.4 kg) who underwent lung transplantation for LAM. Mycophenolate mofetil, tacrolimus (target blood concentration, 4.0-8.0 ng/mL), and prednisolone were administered for immunosuppression, and itraconazole and clarithromycin were administered to manage graft infection. The patient developed unilateral lymphedema, predominantly in the left leg; therefore, sirolimus was initiated with a target blood concentration of 3.0-5.0 ng/mL. In addition to 1.0 mg/day of sirolimus, tacrolimus (0.3 mg/day), itraconazole (100 mg/day), and clarithromycin (800 mg/day) were added. Blood sirolimus concentrations ranged from 18.8 to 36.9 ng/mL on days 6 to 9; thus, treatment with sirolimus was stopped because of over-target blood concentrations. Blood concentrations of sirolimus and tacrolimus were successfully managed without adverse events using therapeutic drug monitoring (TDM) and azole anti-fungal substitution of azithromycin instead of clarithromycin although sirolimus concentration was relatively lower compared to the target range. Thereby, frequent TDM, management of polypharmacy that influences CYP3A activity, and possibly CYP3A genotyping should be appropriately conducted for personalized medicine.
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Evaluation of a Capillary Microsampling Device for Analyzing Plasma Lenvatinib Concentration in Patients With Hepatocellular Carcinoma.
Akihiro Saito, Masafumi Kikuchi, Yuko Matsumoto, Erina Sugawara, Gesshu Takao, Hayato Inomata, Akane Takahashi, Yuji Sato, Masaki Kumondai, Yu Sato, Toshihiro Sato, Masashi Ninomiya, Jun Inoue, Masamitsu Maekawa, Nariyasu Mano
Therapeutic drug monitoring 44 ( 6 ) 771 - 776 2022.12 [Refereed]
Research paper (journal)
BACKGROUND: The anticancer drug, Lenvima (lenvatinib), has severe side effects. Therapeutic drug monitoring helps ensure its efficacy and safety. Regular and optimally timed blood sampling is tough, especially when lenvatinib is self-medicated. Microsampling using the easy to handle Microsampling Wing (MSW) may help circumvent this problem. However, current lenvatinib detection methods are not sensitive enough to detect its concentrations in microsamples (<50-250 μL). Thus, the aim of this study was 2-fold (1) develop an analytic method to estimate plasma lenvatinib concentrations in microsamples and (2) verify whether this method works on micro (5.6 μL) blood plasma samples obtained clinically through MSW from patients with unresectable hepatocellular carcinoma (HCC). METHODS: A simple, highly sensitive, and specific liquid chromatography-electrospray ionization tandem mass spectrometry method was developed. Using this novel protocol, the trough blood plasma concentration of lenvatinib was measured for both blood sampled conventionally and that using MSW. Thirty-five venous whole blood samples were obtained from 11 patients with HCC. Furthermore, the stability of lenvatinib in MSW samples during storage was evaluated. RESULTS: The mean plasma lenvatinib concentration estimates were not significantly different between the MSW and conventional venous blood samples. CV for interday and intraday assays was low. Up to day 5, the lenvatinib concentration in the MSW samples was 85%-115% of the initial day concentration (when stored at 25°C or 4°C). The interference of endogenous matrix components in the human plasma was low. CONCLUSIONS: These results indicate that the novel mass spectrometry protocol accurately measures lenvatinib in human plasma and is reproducible. Thus, MSW could be a useful microsampling device for lenvatinib therapeutic drug monitoring in patients with HCC when used in combination with this novel liquid chromatography-electrospray ionization tandem mass spectrometry detection method.
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Masamitsu Maekawa, Keitaro Miyoshi, Aya Narita, Toshihiro Sato, Yu Sato, Masaki Kumondai, Masafumi Kikuchi, Katsumi Higaki, Torayuki Okuyama, Yoshikatsu Eto, Hiroshi Sakamaki, Nariyasu Mano
Biological and Pharmaceutical Bulletin ( Pharmaceutical Society of Japan ) 45 ( 9 ) 1259 - 1268 2022.09 [Refereed]
Research paper (journal)
As Niemann-Pick disease type C (NPC) is difficult to diagnose owing to its various clinical symptoms; biomarker tests have been developed. Previously, we revealed urinary sulfated cholesterol metabolites as noninvasive biomarkers for NPC. However, LC/tandem mass spectrometry (LC/MS/MS) requires long separation time and large urine volumes. Recently, a basic mobile phase was reported to increase the MS intensity. Thus, we developed a highly sensitive and rapid LC/MS/MS method for analyzing urinary cholesterol metabolites using a basic mobile phase additive. 3β-Sulfooxy-7β-N-acetylglucosaminyl-5-cholenic acid, its glycine and taurine conjugates, 3β-sulfooxy-7β-hydroxy-5-cholenic acid, and 7-oxo form were measured, with selected reaction monitoring in negative ion mode. Oasis HLB and L-column 3 were used for column-switching LC/MS/MS and urine diluted 10-fold was employed as the sample. After trapping, gradient separation was performed using solutions containing 1% (v/v) ammonium solution. On average, a 16-fold increase in peak areas was observed compared to that obtained at pH 5.5 with the mobile phases. Although the previous method needed 60 min for separation from interference peaks, we succeeded to separate them in 7 min with optimized LC condition. Further, all compounds showed good linearity from 0.3-1000 ng/mL, with satisfactory intra- and inter-day reproducibility. The developed method was applied to the urinalysis of healthy participants and NPC patients. Overall, the concentrations of metabolites correlated with those obtained using the previous method. Therefore, we succeeded to increasing MS intensity and shorten LC running time; and the method is useful for the noninvasive diagnostic screening of patients with NPC.
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Minami Yamauchi, Toshihiro Sato, Ayana Otake, Masaki Kumondai, Yu Sato, Masafumi Kikuchi, Masamitsu Maekawa, Hiroaki Yamaguchi, Takaaki Abe, Nariyasu Mano
International Journal of Molecular Sciences ( MDPI AG ) 23 ( 15 ) 8508 - 8508 2022.07 [Refereed]
Research paper (journal)
Patients with liver diseases not only experience the adverse effects of liver-metabolized drugs, but also the unexpected adverse effects of renally excreted drugs. Bile acids alter the expression of renal drug transporters, however, the direct effects of bile acids on drug transport remain unknown. Renal drug transporter organic anion-transporting polypeptide 4C1 (OATP4C1) was reported to be inhibited by chenodeoxycholic acid. Therefore, we predicted that the inhibition of OATP4C1-mediated transport by bile acids might be a potential mechanism for the altered pharmacokinetics of renally excreted drugs. We screened 45 types of bile acids and calculated the IC50, Ki values, and bile acid–drug interaction (BDI) indices of bile acids whose inhibitory effect on OATP4C1 was >50%. From the screening results, lithocholic acid (LCA), glycine-conjugated lithocholic acid (GLCA), and taurine-conjugated lithocholic acid (TLCA) were newly identified as inhibitors of OATP4C1. Since the BDI index of LCA was 0.278, LCA is likely to inhibit OATP4C1-mediated transport in clinical settings. Our findings suggest that dose adjustment of renally excreted drugs may be required in patients with renal failure as well as in patients with hepatic failure. We believe that our findings provide essential information for drug development and safe drug treatment in clinics.
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Simultaneous analysis of remdesivir, favipiravir, and etoposide used to treat COVID-19 infection using liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring
高崎新也, 佐藤稔之, 鈴木博也, 青柳哲史, 青柳哲史, 森下啓, 千葉僚, 佐藤裕, 佐藤紀宏, 菊地正史, 大島謙吾, 徳田浩一, 前川正充, 眞野成康
JSBMS Letters 46 ( Supplement ) 2021
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Fundamental study for the development of LC/ESI-MS/MS method for simultaneous quantification of oral molecular targeted drugs and their metabolites
平澤天晴, 菊地正史, 菊地正史, 高崎新也, 公文代將希, 佐藤裕, 佐藤紀宏, 前川正充, 前川正充, 眞野成康, 眞野成康
JSBMS Letters 46 ( Supplement ) 2021
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インソースCIDを利用したLC/ESI‐MS/MSによる薬物一斉定量法構築への取り組み
菊地正史, 前川正充, 塚本多矩, 眞野成康, 眞野成康
臨床化学 48 ( Suppl.1 ) 162 - 162 2019.08
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インソースCIDを利用したLC/ESI‐MS/MSによる抗がん薬の同時測定法の構築に向けた基礎的検討
平澤天晴, 重田健介, 前川正充, 小倉次郎, 菊地正史, 菊地正史, 眞野成康, 眞野成康
臨床化学 ( (一社)日本臨床化学会 ) 48 ( Suppl.1 ) 251 - 251 2019.08
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第2回病院薬剤師が実践するリバーストランスレーショナルリサーチの最前線〜分子標的探索と個別化医療への挑戦〜 経口分子標的薬の個別化投与設計に向けて
山口 浩明, 高崎 新也, 菊地 正史, 川崎 芳英, 荒井 陽一, 眞野 成康
薬学雑誌 ( (公社)日本薬学会 ) 139 ( 6 ) 911 - 915 2019.06
異なるチロシンキナーゼ阻害薬を服用している腎癌患者の血中濃度を,それぞれの最適条件で同時分析することは困難であり,これまでは各薬物を個別に測定する必要があった.チロシンキナーゼ阻害薬一斉測定法を開発したので概説した.さらに,日本人の腎細胞癌患者におけるスニチニブの有効血中濃度域を明らかにするため,総血中濃度と有害事象および治療継続期間の関連性について解析した.
◆Original paper【 display / non-display 】
◆Other【 display / non-display 】
Grant-in-Aid for Scientific Research 【 display / non-display 】
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Grant-in-Aid for Scientific Research(C)
Project Year： 2021.04 - 2024.03
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Grant-in-Aid for Encouragement of Scientists
Project Year： 2014.04 - 2015.03
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Grant-in-Aid for Encouragement of Scientists
Project Year： 2014.04 - 2015.03
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Grant-in-Aid for Encouragement of Scientists
Project Year： 2014.04 - 2015.03
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Grant-in-Aid for Encouragement of Scientists
Project Year： 2014.04 - 2015.03
Presentations 【 display / non-display 】
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Fundamental study for the development of LC/ESI-MS/MS method for simultaneous quantification of oral molecular targeted drugs and their metabolites
平澤天晴, 菊地正史, 菊地正史, 高崎新也, 公文代將希, 佐藤裕, 佐藤紀宏, 前川正充, 前川正充, 眞野成康, 眞野成康
JSBMS Letters 2021 - 2021
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Simultaneous analysis of remdesivir, favipiravir, and etoposide used to treat COVID-19 infection using liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring
高崎新也, 佐藤稔之, 鈴木博也, 青柳哲史, 青柳哲史, 森下啓, 千葉僚, 佐藤裕, 佐藤紀宏, 菊地正史, 大島謙吾, 徳田浩一, 前川正充, 眞野成康
JSBMS Letters 2021 - 2021
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インソースCIDを利用したLC/ESI‐MS/MSによる抗がん薬の同時測定法の構築に向けた基礎的検討
平澤天晴, 重田健介, 前川正充, 小倉次郎, 菊地正史, 菊地正史, 眞野成康, 眞野成康
臨床化学 2019.08 - 2019.08 (一社)日本臨床化学会
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血中エベロリムス濃度と臨床効果の関連性~腎癌治療における長期追跡調査~
高崎新也, 川崎芳英, 菊地正史, 田中雅樹, 山口浩明, 伊藤明宏, 眞野成康
TDM研究 2019.05 - 2019.05 (一社)日本TDM学会
Academic Activity 【 display / non-display 】
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2024.04-Now
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2023.06-Now
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2023.03-2025.03
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2022.04-Now
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2022.04-Now