CORE--CLINICAL PHARMACOLOGY ANALYTICAL FACILITY

核心--临床药理分析设施

• 批准号: 6989569
• 负责人: MERRILL J EGORIN
• 金额: $ 4.52万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-22 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6989569
• 关键词: analytical chemistry; antineoplastics; biomedical facility; cytochrome P450; experimental designs; genotype; neoplasm /cancer pharmacology; pharmacokinetics; phenotype; protein isoforms

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 PKJPD relationships has resulted in increased emphasis on generating and analyzing such data, even for agents without defined molecular targets. Increased recognition of drug-drug interactions and pharmaco-genetic 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 for the University of Pittsburgh Cancer Institute (UPCI). The CPAF relocated in September 2002 to 1,000 square feet of laboratory space in the Research Pavilion of the Hillman Cancer Center. The CPAF supports preclinical and clinical pharmacology research programs. Services include quantitation of drugs, metabolites, and other materials; identification of metabolites; and PK and PD analyses of anticancer agents that are undergoing clinical trials at UPCI. The CPAF also phenotypes and genotypes cytochrome P450 isoforms and other key drug-metabolizing enzymes. It provides important consultative services to UPCI investigators, on the design of pharmacologic studies and drug assay, metabolism, and PK analyses. The CPAF is directed by Dr. Merrill J. Egorin, with input from Dr. Robert Bies. The Facility is overseen by an advisory committee, representing the Schools of Medicine and Pharmacy, and the Biostatistics Facility. During the past year, the CPAF has provided support for 29 clinical trials at UPCI, 14 CTEP-sponsored clinical trials at other NCI-designated cancer centers, and 54 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. The Facility has acquired two LC/MS instruments and an LC/MS/MS. The CPAF was recognized by Pharsight Corporation as a Center of Pharmaeokinetic Excellence, thereby allowing it to implement sophisticated 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 in ensuring that instrumentation and software are suitably maintained and available for application to projects by investigators seeking support from the Facility.

随着抗癌药物发现和发育已转向分子靶向的疗法，药代动力学（PK）和药效学（PD）的作用显着增加。对PKJPD关系的增强的增强导致人们越来越重视产生和分析此类数据，即使对于没有确定的分子靶标的药物也是如此。对药物代谢，处置和易感性的药物相互作用和药物遗传学差异的认识增加，增加了对定义相关多态性及其临床影响的测定的需求。临床药理学分析设施（CPAF）成立于1994年，旨在为匹兹堡大学癌症研究所（UPCI）提供最新的药理学研究设施。 CPAF于2002年9月搬迁至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支持临床前和临床药理学研究计划。服务包括对药物，代谢产物和其他材料的定量；代谢物的鉴定；以及正在UPCI进行临床试验的抗癌剂的PK和PD分析。 CPAF还表型和基因型细胞色素P450同工型和其他关键的药物代谢酶。它为UPCI研究人员，药物研究和药物测定，代谢和PK分析提供了重要的咨询服务。 CPAF由Merrill J. Egorin博士执导， 罗伯特·比斯（Robert Bies）博士的意见。该设施由咨询委员会监督，代表医学和药学学校以及生物统计学设施。在过去的一年中，CPAF为UPCI的29次临床试验提供了支持，在其他NCI指定的癌症中心进行了14次CTEP赞助的临床试验，以及54个动物药理学项目。它还为3种体外药理学研究提供了分析化学支持。为了扩大其功能并提高其价值，CPAF大大增强了其分析化学仪器，其PK建模软件和人员。该设施已购买了两种LC/MS仪器和一个LC/MS/MS。 CPAF被Pharsight Corporation认可为药物卓越的中心，从而允许其实施复杂的软件。要求的CCSG资金将支持设施人员提供与分析，方法论，协议设计和数据解释相关的咨询服务的努力，以及他们在确保适当维护仪器和软件的努力，并通过寻求该设施的支持的调查人员向项目申请。