記述言語：英語   掲載種別：研究論文（学術雑誌）  

On-site monitoring of plasma drug concentrations is required for effective therapies. Recently developed handy biosensors are not yet popular owing to insufficient evaluation of accuracy on clinical samples and the necessity of complicated costly fabrication processes. Here, we approached these bottlenecks via a strategy involving engineeringly unmodified boron-doped diamond (BDD), a sustainable electrochemical material. A sensing system based on a ∼1 cm2 BDD chip, when analysing rat plasma spiked with a molecular-targeting anticancer drug, pazopanib, detected clinically relevant concentrations. The response was stable in 60 sequential measurements on the same chip. In a clinical study, data obtained with a BDD chip were consistent with liquid chromatography-mass spectrometry results. Finally, the portable system with a palm-sized sensor containing the chip analysed ∼40 μL of whole blood from dosed rats within ∼10 min. This approach with the 'reusable' sensor may improve point-of-monitoring systems and personalised medicine while reducing medical costs.

DOI： 10.1016/j.heliyon.2023.e15963

PubMed

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記述言語：日本語   出版者・発行元：公益社団法人 日本薬理学会  

Measurement of plasma drug concentrations at a clinical site is essential for personalized medicine. For such purpose, the conventional liquid chromatography-mass spectrometry (LC-MS) method is unlikely to be suitable, owing to time and cost consumption. In this study, we describe an approach to rapid, easy, and low-cost drug monitoring with a boron-doped diamond (BDD) electrode, an advanced electrochemical material. As a test drug, we selected pazopanib, an inhibitor for multiple tyrosine kinase types. A small size sensor system with a simple BDD plate electrode of ~26 mm² without any chemical modifications determined the drug concentration in a measurement time of ~35 s from 100 µL rat plasma, which was exogenously mixed with pazopanib. We showed that this system was also applicable to blood samples collected from healthy rats orally administrated with pazopanib as well as drug-treated patients with different cancer types. Notably, all the procedures, including sample preparation and electrochemical measurement, were completed in a short time of ~10 min. The pharmacokinetics data obtained by the BDD electrode were similar to the data determined by LC-MS. Finally, we fabricated a prototype of a palm-sized system, which successfully analyzed ~60 µL of rat blood. This strategy may contribute to advances in on-site drug monitoring.

Based on them, we evaluated plasma samples from five rats orally administered pazopanib and eight clinical patients treated with the drug at our institution. The plasma concentrations and other pharmacokinetic parameters obtained by the BDD method were generally consistent with the LC-MS.

Because this strategy by the BDD sensor is more compact and inexpensive than the LC-MS setup, the electrochemical approach described here can be commonly used and contribute to tailor-made medicine.

DOI： 10.1254/jpssuppl.95.0_2-yia-58

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記述言語：日本語   出版者・発行元：公益社団法人 日本生体医工学会  

経口分子標的薬の抗がん剤は、従来の殺細胞薬に比べ毒性が軽微とされる。それでもなお、患者は堪え難い有害事象に苦しむことが少なくない。原因として、開始用量が患者毎の体表面積に関わらず一定であるため、往々にして過量投与になることが考えられる。対処法として薬を減量すると、用量不足によって効果が減弱することが懸念される。一方、近年開発された分子標的薬のいくつかについては、有効濃度域が不明であり、有害事象の制御が難しい。以上より、投薬法の最適化には、患者一人ひとりに対し、それぞれの薬物の「血中」濃度を測定することが必要である。しかし、臨床の現場では、迅速かつ簡便な測定法が確立していない。そこで本研究では、この困難な課題の解決の基盤となる方法を、従来の素材より安定した反応を示すダイヤモンド電極センサを介した電気化学的アプローチにより創出した。標的薬物として、分子標的薬であるイマチニブ、レンバチニブやパゾパニブ を選択した。ここでは、採取したモルモット血漿に濃度の異なる分子標的薬を単独で添加し、測定法を検証した。その結果、それぞれの臨床濃度域に対応しうる範囲を計測することが可能であった。測定自体は約35秒の短時間で可能であり、サンプル処理を含めても10分以内で全工程が完了した。本計測法を応用すれば、分子標的薬によるテーラーメイド治療が可能になると期待される。

DOI： 10.11239/jsmbe.annual58.286

CiNii Article

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記述言語：日本語   出版者・発行元：公益社団法人 日本薬理学会  

Vancomycin is a glycopeptide antibiotic that kills bacteria by blocking the construction of the cell wall and used to treat different bacterial diseases including meningitis and methicillin‐resistant <i>Staphylococcus aureus</i> infections. Because this antibiotic can sometimes induce renal failure and hearing loss, the plasma concentration is monitored to adjust the dose applied to individual patients. In this study, we show a rapid and simple procedure with an electrochemical approach. The sensor we used consisted of a boron-doped diamond electrode, which elicits more stable reaction than classical materials such as carbon and gold. With this sensor we examined guinea-pig plasma containing vancomycin at different concentrations. The procedure we developed allowed us to complete a series of measurement in 35 sec. Time necessary for all the processes including a sample's pretreatment did not exceed 10 min. The sensor detected the drug concentration of 1 to 50 µM, which falls into the range of the therapeutic window. Moreover, we found that the sensor was repeatedly usable for the measurement with minimal impairment of the sensitivity. The methodology described here may contribute to not only advances in personalized medicine but also reduction of the cost for therapeutic drug monitoring.

DOI： 10.1254/jpssuppl.93.0_1-p-133

CiNii Article

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その他リンク： https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19K16442/

記述言語：日本語   出版者・発行元：公益社団法人 日本薬理学会  

Molecular-targeted anticancer drugs elicit less toxicity than conventional reagents. Yet, patients often suffer from severe adverse effects. A reason is 'fixed dosage' administration of the drug to all the patients regardless of their body size and complications; because of this strategy, the plasma concentration seems to exceed the therapeutic window occasionally. Although frequent measurement of the drug level at a clinical site is a solution, currently available methods such as mass spectrometry are time and cost consuming. To overcome these shortcomings, in this study, we developed a procedure with an electrochemical sensor composed of a conductive diamond, which yields more stable reactions than conventional materials. When guinea-pig plasma mixed with pazopanib, a multi-kinase inhibitor, was tested, the sensor detected a clinically relevant concentration of 3 to 300 µM. Time and sample amount necessary for each series of the measurement was &lt;1 min and 100 µL, respectively. The sensor was repeatedly usable with minimal impairment of the sensitivity, saving the cost for the assay. This rapid and easily-handed method may enable therapeutic drug monitoring and accelerate tailored medicine for cancer.

DOI： 10.1254/jpssuppl.93.0_1-yia-18

CiNii Article

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その他リンク： https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19K16442/

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