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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 ( Journal of Pharmaceutical Health Care and Sciences ) 11 ( 1 ) 20 - 20 2025年03月
研究論文（学術雑誌）
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.
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Hayato Yokota, Kazuhiro Sato, Sho Sakamoto, Yuji Okuda, Masahide Takeda, Yumiko Akamine, Katsutoshi Nakayama, Masatomo Miura
Cancer chemotherapy and pharmacology ( Cancer Chemotherapy and Pharmacology ) 95 ( 1 ) 49 - 49 2025年03月
研究論文（学術雑誌）
PURPOSE: The inflammatory cytokine interleukin (IL)-6 reduces the activity of drug metabolic enzymes and promotes tumor progression. We investigated the effect of IL-6 on the pharmacokinetics of osimertinib and the association between an IL-6 polymorphism and clinical outcomes in 30 patients with non-small cell lung cancer (NSCLC). METHODS: Osimertinib and IL-6 plasma concentrations were measured on day 15 after therapy initiation. The genotype of IL-6 1800796G > C was identified using polymerase chain reaction-restriction fragment length polymorphism. Risk factors affecting overall survival (OS) were assessed by Cox proportional hazard regression analysis. RESULTS: The IL-6 concentration was significantly correlated with the osimertinib trough plasma concentration (r = 0.423, P = 0.020) and area under the plasma concentration-time curve (r = 0.420, P = 0.021). The IL-6 concentration was significantly higher in patients with the IL-6 rs1800796G allele versus C/C genotype (P = 0.024). OS was significantly shorter in patients with the IL-6 rs1800796G allele versus C/C genotype (median: 15.1 vs. 48.9 months, P = 0.005). Univariate and multivariate analyses indicated that the IL-6 rs1800796G allele is an independent risk factor for OS (crude hazard ratio = 7.07; P = 0.014; adjusted hazard ratio = 6.38; P = 0.021). CONCLUSION: A higher IL-6 concentration was associated with reduced metabolic activity of osimertinib, leading to increased osimertinib exposure. As the IL-6 concentration was higher in NSCLC patients with the IL-6 rs1800796G allele, it might be an independent prognostic factor for patients treated with osimertinib.
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Takahiro Kobayashi, Honami Sato, Yumiko Akamine, Yayoi Fukushi, Naoto Takahashi, Masatomo Miura
Xenobiotica; the fate of foreign compounds in biological systems ( Xenobiotica ) 55 ( 1 ) 1 - 6 2024年12月
研究論文（学術雑誌）
The aim of this study was to investigate the effects of renal function and CYP3A5 polymorphism on the drug interaction between venetoclax and fluconazole in thirty acute myeloid leukaemia patients.The area under the plasma concentration-time curve (AUC) and trough concentration (C0) of venetoclax and the fluconazole C0 were obtained from plasma samples on day 7 later after initiation of venetoclax 200 mg/day combined with fluconazole.The fluconazole C0 values in patients with moderate and severe renal impairment were significantly higher than those in patients with normal or mild impairment (median values 7037, 6234, and 4813 ng/mL, respectively, P = 0.026).In patients with CYP3A5*3/*3 genotype, the AUC0-24 and C0 of venetoclax were not associated with fluconazole C0; however, in patients with a CYP3A5*1 allele, a significant positive correlation was observed between venetoclax C0 and fluconazole C0 (r = 0.782, P = 0.004).The metabolism of venetoclax by CYP3A4 is inhibited even at low fluconazole C0. In patients with a CYP3A5*1 allele, CYP3A5 is inhibited when high fluconazole C0 is induced by renal impairment.The dose of fluconazole for prophylaxis may be 100 mg in patients with severe renal impairment receiving venetoclax therapy.
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Hayato Yokota, Yumiko Akamine, Mizuki Kobayashi, Takuro Kitabayashi, Misato Horie, Tentaro Endo, Takechiyo Yamada, Masafumi Kikuchi
Journal of pharmaceutical health care and sciences ( Journal of Pharmaceutical Health Care and Sciences ) 10 ( 1 ) 2024年08月
研究論文（学術雑誌）
BACKGROUND: Naldemedine is an orally available peripherally acting μ-opioid receptor antagonist approved to treat opioid-induced constipation (OIC). It is contraindicated for patients with known or suspected gastrointestinal obstruction to protect against naldemedine-induced perforation. Here, we report a clinical case of suspected perforation of a diverticulum in the sigmoid colon associated with naldemedine. CASE PRESENTATION: The patient was a 65-year-old man with a history of oral cancer who had been prescribed oxycodone (20 mg/day) for cancer pain. On day 0, the patient started naldemedine 0.2 mg once daily before bedtime for OIC. The dose of oxycodone was increased for pain control up to 60 mg/day. On day 35 of naldemedine treatment, the patient developed fever and abdominal pain, and his frequency of defecation had decreased. Initial laboratory results showed a C-reactive protein (CRP) level of 28.5 mg/dL and white blood cell (WBC) count of 13,500/µL. On day 37, the patient still had tenderness in his lower abdomen. Abdominal computed tomography revealed free air in the abdominal cavity suggesting an intestinal perforation. A Hartmann procedure was performed. Histopathological findings showed numerous diverticula in the sigmoid colon, some of which were perforated. CONCLUSIONS: These results suggest that the effects of OIC may have compressed the intestinal tract, which was followed by naldemedine-activation of peristalsis, which led to the onset of intestinal perforation. In patients with pre-existing diverticular disease, we should monitor for increased WBC counts and CRP levels after the initiation of treatment with naldemedine, and consider performing appropriate tests early in the event of abdominal complaints.
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Kazuma Fujita, Yumiko Akamine, Haruka Igarashi, Yayoi Fukushi, Katsuya Sasaki, Koji Fukuda, Masafumi Kikuchi, Hiroyuki Shibata
Japanese journal of clinical oncology ( Japanese Journal of Clinical Oncology ) 54 ( 11 ) 1165 - 1170 2024年06月
研究論文（学術雑誌）
BACKGROUND: The modified Glasgow Prognostic Score (mGPS) and Prognostic Nutritional Index (PNI) are indicators of nutritional status in cancer patients; however, the effects of baseline mGPS and PNI on the duration of administration of the ghrelin receptor agonist anamorelin, which is used to treat cachexia in patients with cancer, are unclear. This study aimed to clarify the association of mGPS and PNI with the duration of oral anamorelin administration for patients who did not have beneficial effects from anamorelin. METHODS: The attending physician determined the duration of oral anamorelin administration based on discontinuation due to cancer progression, poor efficacy, adverse events, or death. RESULTS: The 12-week continuation rate of oral anamorelin was 30.4%. Univariate analysis revealed that an Eastern Cooperative Oncology Group performance status (ECOG-PS) of ≥2 (P < .001), concurrent chemotherapy (P = .002), albumin level (P = .005), C-reactive protein level (P = .013), and a mGPS of 2 (P = .014) were statistically significant predictors of the 12-week continuation rate of oral anamorelin. In the multivariate analysis, a mGPS of 2 remained a significant risk factor, and the ECOG-PS and concurrent chemotherapy had no effect on the association between the mGPS and 12-week continuation rate of oral anamorelin. CONCLUSION: Patients with a mGPS of 2, compared with mGPS of 0 or 1, are less likely to maintain oral anamorelin therapy, regardless of the ECOG-PS or concurrent chemotherapy. Therefore, it is necessary to consider initiating anamorelin administration at mGPS 0 or 1.
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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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新規高速液体クロマトグラフィ分析装置LM1010を用いたclozapineおよびN-desmethylclozapine血中濃度の同時定量の精度評価
赤嶺由美子, 松下美由紀, 森川悟, 三浦昌朋
臨床精神薬理 28 ( 1 ) 87 - 98 2025年01月
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高速液体クロマトグラフィ分析装置LM1010を用いたフェニトインとカルバマゼピンの同時血中濃度定量と化学発光免疫測定法との比較
赤嶺 由美子, 松下 美由紀, 森川 悟, 三浦 昌朋
医療薬学 ( (一社)日本医療薬学会 ) 50 ( 9 ) 465 - 472 2024年09月
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高速液体クロマトグラフィ分析装置LM1010を用いたフェニトインとカルバマゼピンの同時血中濃度定量と化学発光免疫測定法との比較
赤嶺 由美子, 松下 美由紀, 森川 悟, 三浦 昌朋
医療薬学 ( 一般社団法人日本医療薬学会 ) 50 ( 9 ) 465 - 472 2024年09月
<p>LM1010 high-performance liquid chromatography system was recently approved as a medical diagnostic device. Phenytoin and carbamazepine—the antiepileptic drugs—can be detected simultaneously using LM1010; however, the accuracy of quantification of these two drugs in serum using this system has not been established. Herein, we compared the performance of LM1010 in measuring phenytoin and carbamazepine with that of an established chemiluminescent immunoassay (CLIA）using the ARCHITECT system. When CLIA calibrator samples were examined using both methods, the accuracy of LM1010 was within 3.20％ for phenytoin and 6.50％ for carbamazepine. Moreover, the two methods were applied to serum samples from subjects taking phenytoin (n = 95）or carbamazepine (n = 69). The slopes of Deming regression curves comparing LM1010 to CLIA for phenytoin and carbamazepine were 0.984 and 0.943, respectively. Further, Bland–Altman analyses showed an average positive bias (±1.96 × SD）of 0.180 (−1.998 – 2.359）μg/mL for phenytoin and 0.001 (−1.171 – 1.174）μg/mL for carbamazepine using LM1010 relative to CLIA. There were strong correlations between results from LM1010 and CLIA for serum phenytoin and carbamazepine (Spearman’s <i>r</i> = 0.9836 and 0.9754, respectively). The difference in the measurements of serum concentrations of carbamazepine was partially yet significantly negatively correlated with serum hemoglobin (slope = −0.1094). Thus, we successfully applied LM1010 to the simultaneous determination of serum concentrations of phenytoin and carbamazepine and concluded that this system can be used for routine therapeutic drug monitoring.</p>
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【臨床での疑問にこたえる 統計データの読み方,使い方】実践編 ケーススタディから学ぶ臨床での問題・疑問へのアプローチ もしかして,これって副作用?
赤嶺 由美子
薬事 ( (株)じほう ) 66 ( 12 ) 2341 - 2343 2024年09月
＜Key Points＞◎抗精神病薬の多くは,同じ薬剤を同じ投与量で使用しても治療効果や副作用発現に個人差が大きい。◎2022年度の診療報酬改定にて,抗精神病薬であるクロザピンが特定薬剤治療管理料1の対象薬剤として追加となった。治療薬物モニタリングを実施することは,臨床で経験した副作用に対して実際の血中濃度から議論することができるため,非常に有用な手段である。◎システマティックレビューは多くの論文情報が集約されており,エビデンスレベルも高く,効率的に情報を集める手段として非常に有用である。(著者抄録)
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がん悪液質の患者におけるアナモレリン治療継続期間に影響する因子の解明
五十嵐 遥, 藤田 一馬, 福司 弥生, 赤嶺 由美子, 佐々木 克也, 柴田 浩行
日本臨床腫瘍薬学会雑誌 ( (一社)日本臨床腫瘍薬学会 ) 36 277 - 277 2024年05月
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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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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
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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