CLINICAL PHARMACOOOGY ANALYTICAL FACILITY

临床药学分析设施

基本信息

批准号：
8519335
负责人：
Jan Hendrik Beumer
金额：
$ 10.82万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8519335
关键词：
AA Spectrophotometry Advisory Committees Analytical Chemistry Animals Antineoplastic Agents Biological Biological Assay Biometry California Cancer Center Cancer Center Support Grant Cancer Therapy Evaluation Program Cancer and Leukemia Group B Chemicals Clinical Clinical Pharmacology Clinical Trials Computer software Consultations Cytochrome P450 Cytosol Data Data Analyses Detection Development Drug Interactions Drug Kinetics Ensure Enzymes Fluorescence Funding Genetic Polymorphism Goals Guidelines Gynecologic Oncology Group Hepatocyte High Pressure Liquid Chromatography Human Human Resources In Vitro Instruction Laboratories Metabolism Methodology Methods Microsomes Molecular Molecular Target NCI-Designated Cancer Center Pharmaceutical Preparations Pharmacodynamics Pharmacogenetics Pharmacology Pharmacy facility Predisposition Productivity Protein Isoforms Protocols documentation Research Research Activity Research Design Research Personnel Resources Role Sampling Services Subcellular Fractions System Therapeutic Universities University of Pittsburgh Cancer Institute Validation assay development design drug development drug discovery drug metabolism instrument instrumentation liquid chromatography mass spectrometry medical schools meetings novel pharmacodynamic model pharmacokinetic model pre-clinical programs research clinical testing research facility simulation square foot

项目摘要

The role of pharmacokinetics (PK) and pharmacodynamics (PD) has increased dramatically as anticancer drug discovery and development has shifted towards molecularly-targeted therapies. Increased appreciation of PK/PD relationships has resulted in greater emphasis on generating and analyzing such data, even for agents without defined molecular targets. Recognition of drug-drug interactions and pharmacogenetic differences in drug metabolism, disposition, and susceptibility has increased the need for assays to define relevant polymorphisms and their clinical impact. The Clinical Pharmacology Analytical Facility (CPAF) was established in 1994 to provide state-of-the-art pharmacology research facilities forthe University of Pittsburgh Cancer Institute (UPCI). The CPAF occupies 1,000 square feet of laboratory space in the Research Pavilion of the Hillman Cancer Center. The CPAF supports many UPCI CCSG programs in addition to the extensive UPCI preclinical and clinical pharmacology research activities ofthe Molecular Therapeutics and Drug Discovery Program. Services include quantitation of drugs, metabolites, and other materials; identification of metabolites; and PK and PD analyses of anticancer agents undergoing preclinical and/or clinical evaluation at UPCI. The CPAF also uses in vitro methods such as human hepatocyte cultures and subcellular fractions, such as microsomes and cytosol, to characterize the cytochrome P450 isoforms and other key drug-metabolizing enzymes responsible for producing metabolites identified. The CPAF provides important consultative services to UPCI investigators on the design of pharmacologic studies and drug assays, metabolism, and PK analyses. The CPAF is co-directed by Drs. Merrill J. Egorin and Jan H. Beumer and overseen by an advisory committee representing the Schools of Medicine and Pharmacy, and the Biostatistics Facility. During the past 6 years, the CPAF has provided support for 21 Cancer Therapy Evaluation Program (CTEP)-sponsored clinical trials at UPCI, 10 investigator-initiated clinical trials at UPCI, 28 CTEP-sponsored clinical trials at other NCI-designated cancer centers or cooperative groups, and 35 animal pharmacology projects. It also provided analytical chemistry support for 3 in vitro pharmacology studies. To expand its capabilities and increase its value, the CPAF has enhanced substantially its analytical chemistry instrumentation, its PK modeling software, and its personnel. Since the last competitive renewal of the UPCI Cancer Center Support Grant, the Facility has acquired an additional 2 LC-MS instruments and 2 LC-MS/MS instruments. Also since the last competitive renewal, the CPAF competed successfully to serve as the Pharmacology Core Laboratory for the Gynecologic Oncology Group and successfully recompeted its role as the Pharmacology Core for the Cancer and Leukemia Group B. The CPAF continues to be a major collaborator of the University of Southern California Biomedical Simulations Resource, thereby allowing the CPAF to implement sophisticated PK and PD modeling software. The requested CCSG funding will support Facility personnel for their efforts in providing consultative services related to assay development, methodology, protocol design, and data interpretation, and their efforts to ensure that instrumentation and software are suitably maintained and available for application to projects by investigators seeking support from the Facility.

药代动力学（PK）和药效学（PD）作为抗癌药物的作用急剧增加药物发现和开发已转向分子靶向治疗。增加对 PK/PD 关系的认识导致更加重视生成和分析此类数据，即使对于没有明确分子目标的药物。认识药物间相互作用和药物代谢、处置和敏感性方面的药物遗传学差异增加了对药物的需求确定相关多态性及其临床影响的测定。临床药理学分析设施 (CPAF) 成立于 1994 年，旨在为以下领域提供最先进的药理学研究设施：匹兹堡大学癌症研究所 (UPCI)。 CPAF 占地 1,000 平方英尺的实验室空间在希尔曼癌症中心的研究馆。 CPAF 支持许多 UPCI CCSG 计划除了分子中心广泛的 UPCI 临床前和临床药理学研究活动之外治疗和药物发现计划。服务包括药物、代谢物和其他物质的定量材料;代谢物的鉴定；以及抗癌药物的 PK 和 PD 分析 UPCI 的临床前和/或临床评估。 CPAF 还使用体外方法，例如人体肝细胞培养物和亚细胞组分，例如微粒体和胞质溶胶，以表征细胞色素 P450 亚型和其他负责产生的关键药物代谢酶鉴定出代谢物。 CPAF 为 UPCI 调查人员提供重要的咨询服务药理学研究和药物测定、代谢和 PK 分析的设计。 CPAF 共同领导由博士。 Merrill J. Egorin 和 Jan H. Beumer 并由代表该公司的咨询委员会监督医学院和药学院以及生物统计设施。过去6年来，CPAF 为 UPCI 的 21 项癌症治疗评估计划 (CTEP) 赞助的临床试验提供支持，10 研究者在 UPCI 发起的临床试验，在其他 NCI 指定的 28 项 CTEP 赞助的临床试验癌症中心或合作团体，以及35个动物药理学项目。它还提供了分析 3 项体外药理学研究的化学支持。为了扩大其能力并增加其价值， CPAF 大幅增强了其分析化学仪器、PK 建模软件及其人员。自上次 UPCI 癌症中心支持补助金竞争性更新以来，该机构已另外购买了 2 台 LC-MS 仪器和 2 台 LC-MS/MS 仪器。也是自上次比赛以来 CPAF 续签，成功竞聘国家药理学核心实验室妇科肿瘤学组并成功重新发挥其作为药理学核心的作用癌症和白血病 B 组。CPAF 仍然是英国大学的主要合作者南加州生物医学模拟资源，从而使 CPAF 能够实施先进的 PK 和 PD 建模软件。请求的 CCSG 资金将用于支持设施人员表彰他们在提供与检测开发、方法学、实验方案相关的咨询服务方面所做的努力设计和数据解释，以及他们为确保仪器和软件适当而做出的努力维护并可供寻求该基金支持的研究人员应用于项目。