Details of a Researcher - KIKUCHI Masafumi

Development and Clinical Application of a Simultaneous Liquid Chromatography-Tandem Mass Spectrometry Method for Patients with Graft-versus-Host Disease to Quantify the Plasma Concentrations of Ruxolitinib and Posaconazole.

Masaki Kumondai, Nagomi Hayashi, Yu Sato, Daisuke Kobayashi, Ayaka Otsuki, Yugo Ueki, Yasushi Onishi, Taku Tsukamoto, Kohei Yoshikawa, Yoshihiro Hayakawa, Yuji Sato, Toshihiro Sato, Mayumi Sato, Masafumi Kikuchi, Masamitsu Maekawa, Nariyasu Mano

Biological & pharmaceutical bulletin 49 ( 2 ) 301 - 309 2026

Research paper (journal)

Graft-versus-host disease (GVHD) is a clinically significant problem with high mortality that is gradually increasing. Ruxolitinib (RUX) is the only drug used for steroid-refractory GVHD treatment and is thereby crucial. Therapeutic drug monitoring of RUX may be effective because of the relationship between the plasma RUX concentration and treatment outcomes. Posaconazole (PCZ) has also been the recent focus of combined treatment with RUX owing to its pharmacokinetics. We established a simultaneous LC-tandem MS (LC-MS/MS) method and performed plasma drug concentration measurements and monitoring using clinical laboratory values for both RUX and PCZ. We also compared our technique to a simple LC-MS/MS method for clinical application. Moreover, the utility of the automated pretreatment LC-MS/MS (auto-LC-MS/MS) method was tested for further applications. The simultaneous quantification LC-MS/MS method satisfied analytical validation criteria under clinical conditions. Our method demonstrated linearity over the range of 0.3-500 ng/mL for RUX and 3-5000 ng/mL for PCZ, with intra- and inter-day precision and accuracy within ±15%. A possible correlation between plasma RUX concentration and kidney injury was observed in 1 of the 6 patients. Notably, plasma PCZ concentrations were decreased by changing the administration route. Moreover, the plasma concentration levels obtained using the auto-LC-MS/MS method were highly concordant with those obtained using the LC-MS/MS method. The validated LC-MS/MS method was found to be useful in clinical applications; thus, further research into its applications in clinical practice is desirable.

Efficacy of Switching to Levetiracetam After S-1-Induced Phenytoin Concentration Increase: A Case Report.

Hayato Yokota, Haruka Igarashi, Yumiko Akamine, Shinichiro Atsumi, Akise Umakoshi, Masafumi Kikuchi

Cureus 17 ( 4 ) e82653 2025.04 [Refereed]

Research paper (journal)

S-1, an oral anticancer drug, interacts with phenytoin (PHT) to increase PHT serum concentration. Although the PHT dosage is usually adjusted, few studies have examined the effects of switching from PHT to another antiepileptic drug. Here, we report the details of a case in which a patient with gastric cancer continued adjuvant chemotherapy after switching from PHT to levetiracetam (LEV) to prevent interactions with S-1. A man in his 60s with advanced gastric cancer received adjuvant chemotherapy with S-1 120 mg/day (cycles of two weeks of administration followed by one week of rest). He had experienced generalized tonic-clonic seizures 48 years prior and had been taking PHT (170 mg/day) and carbamazepine (250 mg/day). On day 22 of treatment, the PHT concentration increased from 3.72 to 11.76 µg/mL. On day 25, he developed dizziness and fell. Gradual PHT dose reduction and a switch to LEV improved his symptoms, and he remained seizure-free over nine treatment cycles. The findings of this case report suggest an approach for switching from PHT to another antiepileptic drug when PHT levels increase due to interactions with S-1. Switching to LEV may result in fewer interactions.

Effect of isavuconazole on the concentration of tacrolimus in a patient with genotype CYP3A5*1/*3: a case report.

Hayato Yokota, Yumiko Akamine, Harumi Hatakeyama, Hideaki Kagaya, Sho Sakamoto, Mitsuru Saito, Masahide Takeda, Kazuhiro Sato, Katsutoshi Nakayama, Masafumi Kikuchi

Journal of pharmaceutical health care and sciences 11 ( 1 ) 20 - 20 2025.03

Research paper (journal)

BACKGROUND: Azole antifungals are the standard treatment for pulmonary mycosis, which may develop during long-term immunotherapy for kidney transplant. Isavuconazole (ISCZ) is a cytochrome P450 (CYP) 3 A inhibitor that has a risk of interacting with the immunosuppressive drug tacrolimus (TAC). We report a case of simple pulmonary aspergilloma with renal dysfunction due to increased trough levels of TAC after ISCZ coadministration. CASE PRESENTATION: A male in his 60s was treated with TAC 3.0 mg/day orally to prevent graft rejection after kidney transplantation. He received a loading dose of ISCZ 600 mg/day orally for two days, followed by a maintenance dose of 200 mg/day for simple pulmonary aspergilloma. The TAC trough concentration increased markedly from 2.4 to 9.9 ng/mL on day 6 after coadministration. The creatinine level increased from 0.70 to 1.08 mg/dL, suggesting renal dysfunction due to TAC. Subsequently, the TAC dosage was reduced, leading to a decreased blood TAC concentration and improved renal function. The patient's genotype was CYP3A5*1/*3. CONCLUSIONS: In the early stages of ISCZ treatment, the blood TAC concentration is higher, and CYP3A5 polymorphisms may partially explain the extent of this interaction. We recommend more careful monitoring of TAC and serum creatinine levels for approximately one week after ISCZ administration.

Relevance of plasma lenvatinib concentrations and endogenous urinary cytochrome P450 3A activity biomarkers in clinical practice.

Masaki Kumondai, Reika Ogawa, Nagomi Hayashi, Yurika Ishida, Hanae Oshikiri, Yuji Sato, Masafumi Kikuchi, Yu Sato, Toshihiro Sato, Masamitsu Maekawa, Nariyasu Mano

Pharmacology research & perspectives 12 ( 4 ) e1241 2024.08

Research paper (journal)

Lenvatinib (LEN), a multitarget tyrosine kinase inhibitor used in various cancer treatments, is mainly metabolized by cytochrome P450 3A (CYP3A) enzymes. The importance of therapeutic drug monitoring (TDM) in patients administered LEN has been proposed. Although some biomarkers of endogenous CYP3A activity have been reported, their utility in dosage adjustments has not been well evaluated. This study investigated the correlation between plasma LEN concentrations and endogenous urinary CYP3A biomarkers in clinical practice. Concentrations of plasma LEN (N = 225) and CYP3A biomarkers (cortisol, 6β-hydroxycortisol, deoxycholic acid, and 1β-hydroxydeoxycholic acid) in urine (N = 214) from 20 patients (hepatocellular carcinoma, N = 6; thyroid cancer, N = 3; endometrial cancer, N = 8; and renal cell carcinoma, N = 3) collected for consultation for up to 1 year were evaluated using liquid chromatography-tandem mass spectrometry. Moreover, plasma trough LEN concentrations were predicted using a three-compartment model with linear elimination for outpatients administered LEN before sample collection. Moderate correlations were observed between the quantified actual concentrations and the predicted trough concentrations of LEN, whereas there was no correlation with endogenous urinary CYP3A biomarkers. The utility of endogenous urinary CYP3A biomarkers could not be determined. However, TDM for outpatients administered orally available medicines may be predicted using a nonlinear mixed effect model (NONMEM). This study investigated the utility of endogenous urinary CYP3A biomarkers for personalized medicine and NONMEM for predicting plasma trough drug concentrations. These findings will provide important information for further clinical investigation and detailed TDM.

◆Other【 display / non-display 】

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

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

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

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

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.

DOI PubMed CiNii Research

Grant-in-Aid for Scientific Research 【 display / non-display 】

Grant-in-Aid for Scientific Research(C)

Project Year： 2021.04 - 2024.03
Grant-in-Aid for Encouragement of Scientists

Project Year： 2014.04 - 2015.03
Grant-in-Aid for Encouragement of Scientists

Project Year： 2013.04 - 2014.03
Grant-in-Aid for Encouragement of Scientists

Project Year： 2006 - 2006

Presentations 【 display / non-display 】

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
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
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 2019.08 - 2019.08
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
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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2027.03
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