CORE--CLINICAL PHARMACOLOGY ANALYTICAL FACILITY

随着抗癌药物的发现和开发转向分子靶向治疗，药代动力学(PK)和药效学(PD)的作用已显着增加。对PKJPD关系的认识增加了对生成和分析此类数据的重视，即使对于没有确定分子靶标的试剂也是如此。对药物间相互作用和药物代谢、处置和易感性方面的药物遗传学差异的认识增加了对相关多态及其临床影响的分析的需要。临床药理分析设施(CPAF)成立于1994年，为匹兹堡大学癌症研究所(UPCI)提供最先进的药理研究设施。CPAF于2002年9月搬迁到希尔曼癌症中心研究展馆内1000平方英尺的实验室空间。CPAF支持临床前和临床药理学研究计划。服务包括药物、代谢物和其他物质的定量；代谢物的鉴定；以及正在UPCI进行临床试验的抗癌药物的PK和PD分析。CPAF还包括表型和基因类型、细胞色素P450同工酶和其他关键的药物代谢酶。它在药理学研究和药物分析、新陈代谢和PK分析的设计方面为UPCI研究人员提供重要的咨询服务。CPAF由Merrill J.Egorin博士执导， 来自罗伯特·比斯博士的意见。该机构由一个咨询委员会监督，该委员会代表医学院和药学学院，以及生物统计机构。在过去的一年里，CPAF为UPCI的29项临床试验、其他NCI指定的癌症中心由CTEP赞助的14项临床试验和54个动物药理学项目提供了支持。还为3个体外、药理研究提供了分析化学支持。为了扩大能力和增加价值，CPAF大幅加强了分析化学仪器、PK建模软件和人员。该设施购买了两台LC/MS仪器和一台LC/MS/MS。CPAF被Pharsight Corporation认可为药物动力学卓越中心，从而使其能够实施复杂的软件。CCSG申请的资金将支持基金人员努力提供与分析开发、方法学、方案设计和数据解释有关的咨询服务，并努力确保仪器和软件得到适当维护，并可供寻求基金支持的调查人员应用于项目。

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.