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Haruka Igarashi, Hayato Yokota, Ayano Saito, Yumiko Akamine, Naoto Takahashi, Masafumi Kikuchi
Journal of pharmaceutical health care and sciences ( Journal of Pharmaceutical Health Care and Sciences ) 12 ( 1 ) 2026年05月
研究論文（学術雑誌）
BACKGROUND: Voriconazole (VRCZ) is an effective treatment for pulmonary aspergillosis. Active infectious disease leads to a reduction in cytochrome P450 activity, resulting in increased VRCZ concentrations. However, the impact of VRCZ dose reduction during the severe inflammatory state on VRCZ concentrations after the resolution of inflammation is not yet fully understood. Here, we report the time-course changes in VRCZ blood concentrations after inflammation in a patient with invasive pulmonary aspergillosis. CASE PRESENTATION: A man in his 60s receiving oral VRCZ tablets at 400 mg/day for invasive pulmonary aspergillosis developed marked inflammation due to bacterial pneumonia and influenza virus infection. C-reactive protein (CRP) levels increased to a peak of 35.54 mg/dL, with a concomitant elevation in the VRCZ trough concentration to 4.7 µg/mL. Following dose reduction to VRCZ 300 mg/day, the trough concentration decreased to 1.1 µg/mL on day 11 after dose reduction, while CRP declined to 4.78 mg/dL after antibiotic therapy. VRCZ was continued at the same dose. However, four weeks after CRP levels had stabilized, the VRCZ concentration decreased to 0.6 µg/mL. After re-escalation of VRCZ to 400 mg/day, the trough concentration returned to the effective therapeutic range of 1.1 µg/mL. CONCLUSIONS: After infection is controlled, VRCZ concentrations may decrease to levels below the therapeutic range. Following VRCZ dose reduction during a high inflammatory state, reassessment of trough concentrations after improvement of inflammation may be useful to prevent excessive decreases in VRCZ concentrations.
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Yayoi Fukushi, Kazuma Fujita, Yumiko Akamine, Haruka Igarashi, Katsuya Sasaki, Koji Fukuda, Hiroyuki Shibata, Masafumi Kikuchi
Journal of pharmaceutical health care and sciences ( Journal of Pharmaceutical Health Care and Sciences ) 12 ( 1 ) 2026年02月
研究論文（学術雑誌）
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Naoto Takahashi, Yumiko Akamine, Masatomo Miura
European journal of clinical pharmacology ( European Journal of Clinical Pharmacology ) 82 ( 2 ) 49 - 49 2026年01月
研究論文（学術雑誌）
PURPOSE: The effects of polymorphisms in CYP3A4, UGT2B7, ABCB1, ABCG2, ABCC2, NR1I2, and AHR genes on asciminib exposure were evaluated in Japanese patients with chronic myeloid leukemia. METHODS: Plasma concentrations of asciminib (40 mg twice daily [BID] or 80 mg once daily [QD]) were measured by high-performance liquid chromatography. Statistical analysis was performed using SPSS (P < 0.05). RESULTS: For both regimens, the median asciminib area under the concentration-time curve (AUC) was significantly higher in female than in male patients (P = 0.009 and 0.004, respectively). Significant correlations were observed between the asciminib AUC of 40 mg BID or 80 mg QD and body weight (P = 0.042 and < 0.001, respectively). The asciminib AUC0-12 of 40 mg BID in patients with the -25385 T allele of the NR1I2 -25385C > T polymorphism was significantly lower than that in patients with the -25385C/C genotype (5363 and 10607 ng∙h/mL, respectively, P = 0.001). In multiple regression analyses, the NR1I2 -25385C > T polymorphism (P = 0.001) and female sex (P = 0.002) were independently predictive of a higher asciminib AUC0-12 for the 40 mg BID regimen (determination coefficient: 52.8%), whereas body weight (P < 0.001) and female sex (P = 0.047) were independently predictive of a higher asciminib AUC0-24 for the 80 mg QD regimen (determination coefficient: 52.2%). CONCLUSION: Overall, our findings showed that an adjustment of the initial asciminib dose may be needed based on genotyping information for the NR1I2 -25385C > T polymorphism and the body weight of the patient; however, further prospective studies are necessary.
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Drug Interaction Between Erlotinib and Itraconazole in a Patient With Non-Small Cell Lung Cancer.
Hayato Yokota, Satoshi Goshima, Yuji Okuda, Sho Sakamoto, Masahide Takeda, Kazuhiro Sato, Yumiko Akamine, Katsutoshi Nakayama, Masatomo Miura
Case reports in oncological medicine 2026 7788444 - 7788444 2026年
研究論文（学術雑誌）
INTRODUCTION: Erlotinib (ERL) is metabolized primarily by cytochrome P450 (CYP) 3A4. We report a case of non-small cell lung cancer in which plasma ERL concentrations increased following coadministration of itraconazole (ITCZ). CASE PRESENTATION: In this patient, a 67-year-old man receiving ERL 150 mg/day, the trough plasma concentration (C 0) of ERL and its major metabolite, O-desmethyl ERL (OSI-420), increased following coadministration of ITCZ. The total clearance of ERL at steady state was 6.1 L/h. The mean C 0 of ERL and OSI-420 were 437 and 47.1 ng/mL, respectively, and the C 0 ratio of OSI-420/ERL was 0.108. With coadministration of oral ITCZ (200 mg/day capsule), the mean C 0 of ERL and OSI-420 increased to 1124 and 166 ng/mL, respectively, and the mean C 0 ratio of OSI-420/ERL increased to 0.147. The mean C 0 of ITCZ and the sum of ITCZ and the active metabolite hydroxyitraconazole (OH-ITCZ) were 109 and 271 ng/mL, respectively. The mean C 0 of ERL increased approximately 2.5-fold. CONCLUSION: Even at the relatively lower C 0 of ITCZ (compared with the recommended target value), ITCZ coadministration increased the C 0 of ERL. In patients with a sufficient ERL C 0 of more than 500 ng/mL prior to ITCZ coadministration or patients exhibiting adequate absorption of oral ITCZ, the risk of ERL-related adverse events with ITCZ coadministration may increase due to further elevation of the ERL C 0. Therefore, when ERL is coadministered with ITCZ, careful monitoring for adverse effects and appropriate dose adjustments are required, considering potential changes in ERL concentrations. Management using the C 0 of ERL and ITCZ may be necessary.
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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年04月
研究論文（学術雑誌）
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.
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An update on the clinical pharmacokinetics of fexofenadine enantiomers.
Akamine Y and Miura M.
Expert Opinion on Drug Metabolism & Toxicology ( Taylor and Francis Group ) 2018年04月
総説・解説（学術雑誌） 国内共著
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相対モル感度を利用した高速液体クロマトグラフィーによる血液中クロザピンおよびN-脱メチルクロザピン濃度の同時定量法の開発
赤嶺 由美子, 大槻 崇, 松下 美由紀, 松藤 寛, 森川 悟, 三浦 昌朋
医療薬学 ( 一般社団法人日本医療薬学会 ) 52 ( 6 ) 324 - 335 2026年06月
The LM1010 high-performance liquid chromatography (HPLC) system determines the plasma concentrations of clozapine using an absolute calibration method. In this study, the LM1010 HPLC method using relative molar sensitivity (RMS) was developed to quantify the plasma concentrations of clozapine and <i>N</i>-desmethylclozapine. The RMS values were calculated from the ratio of the peak area for clozapine or <i>N</i>-desmethylclozapine to that of highly pure and stable carbamazepine used as an RMS reference. The relative standard deviation of the RMS determined by three different laboratories was 1.723％ for clozapine and 1.821％ for <i>N</i>-desmethylclozapine, suggesting that the mean RMS values of 1.843 and 1.639, respectively, can be used for quantitative analysis in different laboratories. In a retrospective analysis of data obtained from a previous study using a conventional LM1010 method, Deming regression analyses showed a high correlation between the data calculated based on RMS values and the data obtained by HPLC using an internal standard method (slope = 0.942 and 0.974 for clozapine and <i>N</i>-desmethylclozapine, respectively). This result was equivalent to the regression between the results obtained from the LM1010 method using absolute calibration and the HPLC method. A prospective analysis of the RMS method showed strong correlations between RMS and HPLC results (slope = 0.922 and 1.037 for clozapine and <i>N</i>-desmethylclozapine, respectively) and was equivalent to correlations between results obtained from the LM1010 using absolute calibration and the HPLC methods. These findings suggest that the RMS method is suitable for the quantitative assay of plasma concentrations of clozapine and <i>N</i>-desmethylclozapine and offers an alternative to the current absolute calibration method.
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併存疾患もまるごと最適化しよう 持病のある患者ががんになったら 慢性疾患を合併したがん患者のマネジメント 精神・神経疾患患者が,がんになったら
赤嶺由美子
月刊薬事 68 ( 8 ) 2026年
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五苓散の網羅的臨床検査値解析による新規薬効の探索とアクアポリン関連機序の検討
阿部史葉, 阿部史葉, 佐藤(沼田)かお理, 赤嶺由美子, 沼田朋大
日本薬学会年会要旨集(Web) 146th 2026年
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The impact of NR1I2 gene polymorphism and body weight on asciminib pharmacokinetics in patients with chronic myeloid leukemia
Naoto Takahashi, Yumiko Akamine, Masatomo Miura
BLOOD 146 2025年11月
研究発表要旨（国際会議）
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薬事【血中濃度の変動要因を見極めよう 悩ましい薬物動態の諸問題】実践編 薬剤別マネジメント 向精神薬(解説)
赤嶺 由美子 ( 担当： その他 )
(株)じほう 2024年
産業財産権 【 表示 ／ 非表示 】
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クロザピン又はその誘導体の血中薬剤濃度上昇リスク判定方法及び薬剤投与量判定方法
特許
特願 特願2016-092152 特開 特開2017-195862 特許 特許第6807094号
出願日： 2016年04月29日
公開日： 2017年11月02日
赤嶺 由美子, 三浦 昌朋
学術関係受賞 【 表示 ／ 非表示 】
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日本医療薬学会奨励賞
2022年09月24日 一般社団法人日本医療薬学会 精神科領域における個別化薬物療法の開発
受賞者： 赤嶺由美子 -
女性研究者支援コンソーシアムあきた賞
2020年11月26日 秋田県 患者血液中マーカーを用いた 精神科領域の個別化薬物療法の確立
受賞者： 赤嶺由美子 -
秋田県病院薬剤師会臨床薬学賞
2020年06月06日 一般社団法人秋田県病院薬剤師会 精神科領域における 個別化薬物療法の確立
受賞者： 赤嶺由美子 -
第27回日本医療薬学会年会 優秀演題賞
2017年11月04日 一般社団法人日本医療薬学会 ACMIA, CLIA, ECLIA, LTIA法によるタクロリムス血中濃度測定値へのCYP3A5遺伝子多型の影響
受賞者： 赤嶺由美子,加賀谷英彰, 佐藤滋, 三浦 昌朋 -
日本薬学会九州支部 学術奨励賞
2013年12月07日 日本薬学会九州支部 フェキソフェナジンの立体選択的体内動態とその規定因子の解析
受賞者： 赤嶺由美子
科研費（文科省・学振）獲得実績 【 表示 ／ 非表示 】
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日本人統合失調症患者におけるクロザピン個別化投与モデルの開発
基盤研究(C)
研究期間: 2026年04月 - 2029年03月 代表者: 赤嶺 由美子
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抗精神病薬誘発性代謝異常に関するメカニズム研究
基盤研究(C)
研究期間: 2021年04月 - 2025年03月 代表者: 赤嶺 由美子
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抗精神病薬誘発性代謝異常に関するメカニズム研究
基盤研究(C)
研究期間: 2021年04月 - 2025年03月 代表者: 赤嶺 由美子
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抗精神病薬誘発性代謝異常に関するメカニズム研究
基盤研究(C)
研究期間: 2021年04月 - 2025年03月 代表者: 赤嶺 由美子
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抗精神病薬誘発性代謝異常に関するメカニズム研究
基盤研究(C)
研究期間: 2021年04月 - 2025年03月 代表者: 赤嶺 由美子
その他競争的資金獲得実績 【 表示 ／ 非表示 】
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クロザピン活性代謝物血中濃度測定の臨床的意義に関する研究
提供機関: 民間財団等 先進医薬研究振興財団
研究期間： 2018年12月 - 2019年11月 代表者: 赤嶺由美子
資金支給機関区分：民間財団等
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PK-PD-PGx に基づいたクロザピン個別化療法の確立
提供機関: 民間財団等 薬学研究奨励財団
研究期間： 2016年04月 - 2019年03月 代表者: 赤嶺由美子
資金支給機関区分：民間財団等
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クロザピンの個別化治療の確立
提供機関: 民間財団等 臨床薬理研究振興財団
研究期間： 2016年04月 - 2017年10月 代表者: 赤嶺由美子
資金支給機関区分：民間財団等