研究等業績 - その他 - 奥田 佑道
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Yokota H.
Journal of Pharmaceutical Health Care and Sciences ( Journal of Pharmaceutical Health Care and Sciences ) 10 ( 1 ) 2024年12月
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Sakamoto S.
Current Problems in Cancer: Case Reports ( Current Problems in Cancer: Case Reports ) 10 2023年06月
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秋田県における新型コロナウイルス感染症の流行が高齢者の肺がん検診に与えた影響について
奥田 佑道, 浅野 真理子, 佐藤 一洋, 大本 瑛己, 坂本 祥, 竹田 正秀, 清水 辰徳, 大田 秀隆, 中山 勝敏
日本老年医学会雑誌 ( (一社)日本老年医学会 ) 60 ( Suppl. ) 182 - 182 2023年05月
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Yokota H.
Cancer Chemotherapy and Pharmacology ( Cancer Chemotherapy and Pharmacology ) 92 ( 4 ) 315 - 324 2023年
PURPOSE: Because of the large interindividual variability of afatinib pharmacokinetics and adverse events, we evaluated the effects of polymorphisms in pregnane X receptor (NR1I2) and ABC transporters (ABCB1, ABCG2, and ABCC2) on the pharmacokinetics of afatinib. METHODS: The steady-state area under the concentration-time curve (AUC)0-24 of afatinib was analyzed using blood sampling just prior to and at 1, 2, 4, 6, 8, 12, and 24 h on day 15 after administration. RESULTS: The median oral clearance (CL/F) of afatinib in patients with the NR1I2 7635A allele was significantly lower than those in patients with the 7635G/G genotype (42.0 and 60.0 L/h, respectively, P = 0.025). There were no significant differences in afatinib CL/F between genotypes for NR1I2 8055C > T, -25385C > T, ABCB1, ABCG2, and ABCC2 polymorphisms. Based on the area under the receiver-operating characteristic curve, the threshold afatinib AUC0-24 value for prediction of dose reduction or withdrawal was 689 ng·h/mL at the best sensitivity (81.0%) and specificity (72.7%). In multivariate logistic regression analysis, an afatinib AUC0-24 above 689 ng·h/mL was independently associated with increased risk of dose reduction or withdrawal (OR: 11.66, P = 0.012). CONCLUSIONS: The NR1I2 7635A allele was related to a lower afatinib CL/F. Based on the AUC of 689 ng h/mL and CL/F, the optimal doses for patients with the NR1I2 7635G/G genotype and 7635A allele were recommended to be set at 40 and 30 mg/day, respectively, and subsequent adjustment of the maintenance dose based on the plasma concentrations of afatinib may be necessary to avoid afatinib-related adverse events.
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Yokota H.
Investigational New Drugs ( Investigational New Drugs ) 40 ( 6 ) 1254 - 1262 2022年12月
The effects of polymorphisms in CYP3A4 (20230G > A), CYP3A5 (6986A > G), ABCB1 (1236C > T, 2677G > T/A, 3435C > T), ABCG2 (421C > A), and ABCC2 (-24C > T) on the area under the concentration-time curve (AUC) of osimertinib in 23 patients with non-small cell lung cancer were investigated. Blood sampling was performed just prior to and at 1, 2, 4, 6, 8, 12, and 24 h after osimertinib administration at the steady-state on day 15 after beginning therapy. The osimertinib AUC0-24 was significantly correlated with age (P = 0.038), serum albumin (P = 0.002), and serum creatinine (P = 0.012). Additionally, there were significant differences in the AUC0-24 of osimertinib among the groups administered vonoprazan, histamine 2-receptor antagonists or esomeprazole, and no acid suppressants (P = 0.021). By contrast, there were no significant differences in the AUC0-24 of osimertinib between genotypes of CYP3A4/5 or ABC transporters. Furthermore, there were no significant differences in the AUC0-24 of osimertinib between patients with diarrhea, skin rash, or hepatotoxicity and those without these conditions. In multivariate analysis, only serum albumin value was an independent factor predicting the AUC0-24 of osimertinib. Analysis of CYP3A4/5 and ABC transporter polymorphisms before osimertinib therapy may not predict the efficacy or side effects of osimertinib. The lower serum albumin values were associated with an increase in the AUC0-24 of osimertinib; however, further studies are needed to assess the factors contributing to the interindividual variability of osimertinib pharmacokinetics.
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オシメルチニブによる薬剤性肺障害が疑われた高齢者肺癌の1例
浅野 真理子, 佐藤 一洋, 坂本 祥, 奥田 佑道, 竹田 正秀, 佐野 正明, 横田 隼人, 三浦 昌朋, 大田 秀隆, 中山 勝敏
日本老年医学会雑誌 ( (一社)日本老年医学会 ) 59 ( 4 ) 575 - 575 2022年10月
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高齢で診断された肺動静脈奇形を合併した遺伝性出血性末梢血管拡張症の1例
奥田 佑道, 佐藤 一洋, 五島 哲, 旭 ルリ子, 泉谷 有可, 坂本 祥, 浅野 真理子, 竹田 正秀, 大田 秀隆, 中山 勝敏
日本老年医学会雑誌 ( (一社)日本老年医学会 ) 59 ( 4 ) 576 - 576 2022年10月
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Shimizu T.
Japanese Journal of Geriatrics ( Japanese Journal of Geriatrics ) 59 ( 4 ) 543 - 550 2022年
<p><b>目的：</b>認知症地域支援推進員の効率的な事業展開に向けて必要なことを検討する．<b>方法：</b>当センターがある秋田県において，25市町村の認知症地域支援推進員を対象に活動の現状を把握し，事業を効率的に展開するためにはどういったことが必要かを検討するための簡易アンケート調査を行った．<b>結果：</b>第一に認知症支援推進員の存在を地域住民に認知されていないことが判明し，その存在や活動を周知するような機会が必要であることが明らかになった．また推進員同士の情報共有や認知症の支援体制を構築するための社会資源を把握するツールなどが不足していることも明らかになった．また連携の面では，初期集中支援チームや疾患医療センターとの連携はとれているものの，認知症サポーターとの連携が不十分であることが判明した．さらに推進員の大きな役割である認知症ケアパスの作成や活動にはあまり関与しない実態が見えてきた．<b>結論：</b>今回の結果より，事業を効率的に展開するためのポイントとして，1．地域住民に対する認知症地域推進員を周知するための情報発信，2．認知症サポーターや民生委員との連携づくり，3．社会資源マップの作成やその把握，認知症ケアパスの有効活用，4．地域支援推進員が兼務しなくてよい労働環境の整備，5．認知症施策全体を理解するための学習の場づくり，の以上5点を提案する．</p>
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当院における高齢者非小細胞肺癌に対するニボルマブの効果
奥田佑道, 浅野真理子, 佐藤一洋, 熊谷奈保, 坂本祥, 竹田正秀, 小玉鮎人, 大田秀隆, 中山勝敏
日本老年医学会雑誌 59 2022年
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Yokota H.
Biology ( Biology ) 10 ( 10 ) 2021年10月
We evaluated the area under the plasma concentration-time curve (AUC) of afatinib required to avoid the onset of grade 2 or higher diarrhea. The C0 and AUC0-24 of afatinib were significant higher in patients with grade 2 diarrhea than in those with grade 0-1 diarrhea. The areas under the receiver operator curves were 0.795 with the highest sensitivity (89%) and specificity (74%) at an AUC0-24 threshold of 823.5 ng·h/mL, and 0.754 with the highest sensitivity (89%) and specificity (74%) at a C0 threshold of 28.5 ng/mL. In Kaplan-Meier analysis based on these cut-off AUC0-24 and C0 values, the median time to the incidence of grade 2 diarrhea was 16 days. The predicted AUC0-24 of afatinib from the single point of C6 showed the highest correlation with the measured AUC0-24 (r2 = 0.840); however, a significant correlation between the AUC0-24 and C0 was also observed (r2 = 0.761). C0 could be used as a marker of therapeutic drug monitoring because afatinib C0 was related to AUC0-24. Therefore, afatinib C0 should be monitored on day 8 after beginning therapy, and the daily dose of afatinib should be adjusted as an index with a cut-off value of 28.5 ng/mL.
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Eosinophil extracellular traps in a patient with chronic eosinophilic pneumonia
Takeda M.
Asia Pacific Allergy ( Asia Pacific Allergy ) 11 ( 3 ) e24 2021年07月
Eosinophils rapidly release extracellular filamentous chromatin fibers (extracellular traps, ETs) when they are stimulated. Reticulated ETs have been recently shown to affect secretion viscosity in eosinophilic inflammatory diseases. Here we report a 43-year-old woman with infiltrative shadows in both upper lungs that did not respond well to antibiotics. She admitted to occasional coughing and sputum, but had poor viscous regulation. Bronchoalveolar lavage fluid (BALF) collected from the upper left lobe showed many eosinophils (65%). She was diagnosed with chronic eosinophilic pneumonia, per previously reported criteria, and began treatment with prednisolone. The infiltration shadow gradually improved, and she was discharged 28 days after admission. Later, we immune-stained her BALF cell components with antibodies against major basic protein, an eosinophil granule protein, which showed a large number of agglomerating eosinophils; and antibodies against citrullinated histone H3 (CitH3-a marker for ETs), which showed CitH3-positive ETs, spread in a network. These findings confirmed that some BALF eosinophils released eosinophil ETs. This case shows the existence of ETs from BALF in patients with chronic eosinophilic pneumonia. Concentration of eosinophil ETs in eosinophilic inflammatory diseases may affect secretion viscosity in sputum, and so on.
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gefitinibの血中濃度と薬物動態に関する遺伝子多型との関係性についての検討
坂本 祥, 佐藤 一洋, 横田 隼人, 赤嶺 由美子, 奥田 佑道, 浅野 真理子, 竹田 正秀, 三浦 昌朋, 中山 勝敏
日本呼吸器学会誌 ( (一社)日本呼吸器学会 ) 10 ( 増刊 ) 208 - 208 2021年04月
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Unusual morphologies of blood eosinophils in GM-CSF-producing lung cancer
Izumiya Y.
QJM : monthly journal of the Association of Physicians ( QJM : monthly journal of the Association of Physicians ) 114 ( 1 ) 42 - 44 2021年02月
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Unusual morphologies of blood eosinophils in GM-CSF-producing lung cancer
Izumiya Y.
QJM ( QJM ) 114 ( 1 ) 42 - 44 2021年01月
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Kodama A.
Japanese Journal of Geriatrics ( Japanese Journal of Geriatrics ) 58 ( 2 ) 266 - 271 2021年
<p>本研究の目的は，認知症初期集中支援チーム構成員を対象としたアンケート調査を実施し，秋田県内における認知症初期集中支援チームの活動動向を明らかにするとともに，今後の事業のさらなる効率的な推進に寄与すべく要因を明らかにすることである．県内の認知症初期集中支援チーム構成員46名を対象として，合計10項目からなるアンケート調査を実施した．その結果，認知症地域支援推進員や認知症疾患医療センターとの連携体制は概ね確立されているものの，居宅訪問を含めたかかりつけ医との連携が不十分であることが問題点として挙げられた．また，これまでも認知症初期集中支援チームにおける課題として取り上げられている認知症者の早期発見に対しては，この支援チームの存在を知ってもらうための地域住民に向けた周知・啓発や支援チームの介入のために本人ばかりでなく，ご家族との信頼関係の構築が重要であることが示唆された．</p>
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EML4-ALK融合遺伝子陽性の高齢者肺癌の1例
奥田佑道, 奥田佑道, 佐藤一洋, 長谷川幸保, 滝田友里, 泉谷有可, 熊谷奈保, 浅野真理子, 浅野真理子, 竹田正秀, 大田秀隆, 中山勝敏
日本老年医学会雑誌 58 ( 4 ) 2021年
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gefitinibの血中濃度と薬物動態に関する遺伝子多型との関係性についての検討
坂本祥, 佐藤一洋, 横田隼人, 赤嶺由美子, 奥田佑道, 浅野真理子, 竹田正秀, 三浦昌朋, 中山勝敏
日本呼吸器学会誌(Web) 10 2021年
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Sakamoto S.
Investigational New Drugs ( Investigational New Drugs ) 38 ( 6 ) 1687 - 1695 2020年12月
ATP-binding castle protein G2 (ABCG2) is thought to inhibit the activities of certain gefitinib transporters, thereby affecting drug pharmacokinetics. The C421A polymorphism affects the function and expression of ABCG2 on the cell membrane. Previous studies have shown that proton-pump inhibitors (PPIs) inhibit gefitinib absorption, as well as the function of ABCG2. We evaluated the plasma concentrations of gefitinib in patients with and without the ABCG2 C421A polymorphism, who were or were not taking PPIs. In total, 61 patients with advanced epidermal-growth-factor-positive non-small-cell lung cancer were enrolled in this study. They were treated with gefitinib at a dose of 250 mg per day. Plasma gefitinib concentration and ABCG2 C421A status were determined after 2 weeks. The patients were divided into CC- and CA/AA genotype groups. We compared the trough and peak gefitinib levels and the area under the curve (AUC) values for 24-h gefitinib concentrations. We also compared these parameters among four groups distinguished according to the presence or absence of the polymorphism and PPI use. The mean trough gefitinib level and AUC value for 24-h gefitinib concentration were significantly lower in the CA/AA group compared to the CC group (mean trough level: 333.2 vs. 454.5 ng/mL, respectively, P = 0.021; AUC: 9949.9 vs. 13,085.4 ng・h/mL, respectively, P = 0.034). Among patients taking PPIs, the mean trough gefitinib level was significantly lower in the CA/AA group than the CC group (220.1 vs. 340.5 ng/mL, respectively, P = 0.033). The CA/AA-type of ABCG2 C421A polymorphism may be associated with lower gefitinib plasma concentrations.
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熊谷 奈保, 滝田 友里, 泉谷 有可, 坂本 祥, 長谷川 幸保, 浅野 真理子, 奥田 佑道, 竹田 正秀, 佐野 正明, 佐藤 一洋, 中山 勝敏, 高嶋 祉之具, 今井 一博, 南谷 佳弘, 南條 博
肺癌 ( (NPO)日本肺癌学会 ) 60 ( 7 ) 1032 - 1032 2020年12月