Development of Evaluation system of Drug Metabolism Ability for Personalized Medicine using Environmentally Responsive Polymers

环境响应型聚合物个体化医疗药物代谢能力评价系统的开发

• 批准号: 18590038
• 负责人: KANAZAWA Hideko
• 金额: $ 2.51万
• 依托单位: Kyoritsu University of Pharmacy
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590038/
• 关键词: poly(N-isopropylacrylamide); temperature-responsive chromatography; cytochrome P450; environmentally responsive; personalized medicine; therapeutic drug monitoring

Hepatic drug oxidation is a major source of interindividual variations in drug pharmacokinetics and therapeutic response. In vitro cytochrome P450 assays are used in metabolism studies in support of early phases of drug discovery to investigate, e. g., metabolic stability, enzyme inhibition and induction by new chemical entities. In this study, we investigated the separation of probe substrates of cytochrome P450 using temperature-responsive chromatographic system. Temperature-dependent resolution of 6 kinds of probe substrates which commonly used by the pharmaceutical industry to study in vitro drug interactions was achieved using only an isocratic aqueous solution as a mobile phase. The separation of probe drugs and its metabolites was also achieved by temperature changes without any changes in the mobile phase. In this system, the simultaneous separation of probe drugs and its metabolites was achieved by using only an aqueous solution as a mobile phase. Moreover, therapeutic drug monitoring of antiepileptic drugs with direct plasma injection without any pretreatment was achieved by the proposed system using only water as a mobile phase. This system is simple, convenient and expects to be useful for drug analysis in clinical field for personalized medicine.

肝脏药物氧化是药物药代动力学和治疗反应个体间差异的主要来源。体外细胞色素P450测定用于代谢研究，以支持药物发现的早期阶段，例如。例如，在一个实施例中，代谢稳定性、酶抑制和新化学实体的诱导。本文研究了温度响应色谱系统分离细胞色素P450探针底物的方法。采用等度水溶液作为移动的流动相，实现了6种常用探针底物的温度依赖性分离。探针药物及其代谢物的分离也通过温度变化而实现，而移动的相没有任何变化。在该体系中，探针药物及其代谢物的同时分离，仅使用水溶液作为移动的相。此外，治疗药物监测抗癫痫药物的直接血浆注射，而无需任何预处理，实现了所提出的系统仅使用水作为移动的相。该系统操作简单、使用方便，有望在临床药物分析领域为个体化用药提供参考。

项目成果

温度応答性クロマトグラフィーによる鎮静・麻酔薬の血中濃度測定への応用.

温度响应色谱法在镇静麻醉药血药浓度测定中的应用

• 发表时间: 2007
• 作者: 鈴木 理恵;鈴木 祐輔;金澤 秀子.
• 通讯作者: 金澤 秀子.

温度応答性クロマトグラフィーを用いた水系移動相による医薬品及び生体分子の分析.

使用温度响应色谱法使用水性流动相分析药物和生物分子。

• 发表时间: 2007
• 作者: 鈴木 祐輔;金澤 秀子;菊池 明彦;岡野 光夫.
• 通讯作者: 岡野 光夫.

Analysis of Melatonin using pH- and Temperature-responsive Aqueous Chromatographic System

使用 pH 和温度响应型水相色谱系统分析褪黑激素

• 发表时间: 2007
• 期刊: J Health Sci 53
• 作者: E.;Ayano;Y.;Suzuki;M.;Kanezawa;C.;Sakamoto;Y.;Morita;Y.;Nagata;H.;Kanazawa;A.;Kikuchi;T.;Okano
• 通讯作者: Okano

Defbrential effbcts of the ascorbyl and tocopheryl derivative on the methamphetamineinduced toxic behavior and toxicity.

抗坏血酸和生育酚衍生物对甲基苯丙胺诱导的毒性行为和毒性的去纤维作用。

• 发表时间: 2007
• 期刊: Toxicology 240
• 作者: Ito S;Mori T;Kanazawa H;Sawaguchi T.
• 通讯作者: Sawaguchi T.

Study of a Capillary LC System using Temperature-Responsive Polymer-Modified Packing Materials

使用温度响应型聚合物改性填料的毛细管液相色谱系统的研究

• 发表时间: 2006
• 期刊: CHROMATOGRAPHY 27
• 作者: M.Kanezawa;E.Ayano;H.Kanaz awa;Y.Akiyama and T.Okano
• 通讯作者: Y.Akiyama and T.Okano