Pharmacoanalytical

药物分析

基本信息

批准号：
8555665
负责人：
KENNETH K CHAN
金额：
$ 12.64万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-09-12 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8555665
关键词：
Antineoplastic Agents Applications Grants Area Under Curve Biological Biological Assay Biological Availability Biological Factors Cancer Center Support Grant Clinical Clinical Drug Development Clinical Protocols Clinical Trials Communities Comprehensive Cancer Center DNA Methylation Data Data Analyses Decitabine Development Dose Drug Kinetics Employee Equipment Experimental Designs Funding Goals Grant Growth High Pressure Liquid Chromatography Hour Housing Human Resources Instruction Laboratory Research Methods Nucleosides Oblimersen Ohio Patients Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Pharmacy (field)Pharmacy facility Plasma Process Publications Reporting Research Design Research Personnel Resource Sharing Resources Ribonucleotide Reductase Running Sampling Schedule Services Specimen System Time Toxic effect Universities Validation Work analytical method clinical decision-making college cost cost effective data modeling design drug development experience flavopiridol inorganic phosphate instrumentation mass spectrometer member metabolic abnormality assessment method development novel pharmacokinetic model pre-clinical programs response silvestrol success ultra high pressure

项目摘要

PROJECT SUMMARY (See instructions): The Ohio State University Comprehensive Cancer Center (OSUCCC) Pharmacoanalytical Shared Resource (PhASR) has been in development since 2004. PhASR provides bioanalytical method development, quantitative sample analysis, and pharmacokinetic/pharmacodynamic (PK/PD) experimental design and data analysis to support pre-clinical and clinical cancer drug development. PhASR's objectives are to provide: 1) high-quality, state-of-the-art analytical expertise and instrumentation for quantitation of drugs and metabolites in biological specimens at cost-competitive rates; 2) PK/PD data for incorporation into clinical decision-making; and 3) expertise in PK/PD study design and data interpretation to support submission of clinical protocols, grants, and publications. PhASR is directed by Dr. Kenneth K. Chan, with additional support from Technical Director, Dr. Mitch A. Phelps. An additional staff of 2.70 full-time employees provides support for sample processing, method development and PK/PD data analysis and modeling. Outstanding institutional support is provided by the OSUCCC and College of Pharmacy's Division of Pharmaceutics that houses the fully-equipped pharmaceutical research laboratories of Drs Chan and Phelps which comprise PhASR. Major equipment in PhASR includes 3 LC-MS systems and 2 stand-alone LC-UV systems ideally suited for drug quantitation and metabolite identification. These systems include a quadrupole-time-of-flight and two triple-quadrupole mass spectrometers, one of which is supported by an ultra-high pressure liquid chromatography system expandable for automated sample processing and high throughput enalysis. Additional LC-MS systems to develop and run biological correlative assays are available. By leveraging outstanding institutional partnerships, PhASR is able to offer its services to OSUCCC members at reduced rates. In the past 12 months PhASR staff has analyzed more than 2,600 samples and has logged nearly 1,700 hours for analytical method development and PK/PD experimental design and data analysis. Neariy 95% of this activity supported 27 members in 5 of the 6 programs within the OSUCCC. Recent highlights of work by PhASR researchers include design of an active flavopiridol dosing schedule and pharmacokinetic modeling of data from 8 clinical trials; development, validation and application of ultrasensitive assays (pM) to support clinical investigations of Bcl-2 and ribonucleotide reductase targeted antisense therapies (G3139 and GTI-2040); validation and application of methods for quantitation of low dose decitabine and resulting intracellular endogenous nucleoside and drug phosphates and global and regional DNA methylation; and pre-clinical pharmacokinetic and metabolism studies of the novel natural product, silvestrol, now in pre-clinical development by the OSUCCC and the NCI. In its short time as a developing resource, PhASR has made these and other significant contributions resulting in high impact publications, grant proposals and funding for OSUCCC investigators. Institutional support and OSUCCC investigators' recognition of the quality of PhASR capabilities and services have insured the continued growth and success of this highly valued shared resource.

项目摘要（参见说明）：俄亥俄州立大学综合癌症中心 (OSUCCC) 药物分析共享资源 (PhASR) 自 2004 年以来一直在开发。PhASR 提供生物分析方法开发、定量样品分析以及药代动力学/药效 (PK/PD) 实验设计和数据分析，以支持前期研究-临床和临床癌症药物开发。 PhASR 的目标将提供： 1) 高质量、最先进的分析专业知识和仪器，以具有成本竞争力的价格定量生物样本中的药物和代谢物； 2) PK/PD数据纳入临床决策； 3) PK/PD 研究设计和数据解释方面的专业知识，以支持临床方案、资助和出版物的提交。 PhASR 由 Kenneth K. Chan 博士指导，技术总监 Mitch A. Phelps 博士提供额外支持。另外还有 2.70 名全职员工为样品处理、方法开发以及 PK/PD 数据分析和建模提供支持。 OSUCCC 和药学院药剂学部提供了出色的机构支持，该部门设有陈博士和菲尔普斯博士（PhASR）设备齐全的药物研究实验室。 PhASR的主要设备包括3套LC-MS系统和2套独立的 LC-UV 系统非常适合药物定量和代谢物鉴定。这些系统包括一个四极杆飞行时间质谱仪和两个三重四极杆质谱仪，其中一个由超高压液相色谱系统支持，可扩展用于自动样品处理和高通量分析。用于开发和运行生物技术的附加 LC-MS 系统可以进行相关分析。通过利用杰出的机构合作伙伴关系，PhASR 能够以较低的价格向 OSUCCC 成员提供服务。在过去 12 个月中，PhASR 工作人员分析了 2,600 多个样本，并记录了近 1,700 小时的分析方法开发、PK/PD 实验设计和数据分析时间。这项活动的近 95% 支持了 6 个中的 5 个中的 27 名成员 OSUCCC 内的项目。 PhASR 研究人员最近的工作重点包括设计活性黄吡醇给药方案以及对 8 项临床试验数据进行药代动力学建模；超灵敏测定 (pM) 的开发、验证和应用，以支持 Bcl-2 和核糖核苷酸还原酶靶向反义疗法（G3139 和 GTI-2040）的临床研究；低剂量地西他滨和由此产生的细胞内内源核苷和药物磷酸盐以及整体和区域 DNA 甲基化定量方法的验证和应用；和临床前新型天然产物西维甾醇的药代动力学和代谢研究，目前由 OSUCCC 和 NCI 进行临床前开发。在作为开发资源的短暂时间内，PhASR 做出了这些和其他重大贡献，为 OSUCCC 研究人员提供了高影响力的出版物、资助提案和资金。机构支持和 OSUCCC 研究人员对 PhASR 能力和服务质量的认可确保了这一高度重视的持续增长和成功共享资源。