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）的作用显著增加。越来越多的赞赏PKJPD的关系，导致越来越重视产生和分析这样的数据，即使是没有明确的分子靶点的代理。对药物间相互作用和药物代谢、处置和易感性的药物遗传学差异的认识增加，增加了对确定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，为匹兹堡大学癌症研究所（UPCI）提供最先进的药理学研究设施。该CPAF于2002年9月搬迁到希尔曼癌症中心研究馆的1,000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药物的PK和PD分析。CPAF还对细胞色素P450亚型和其他关键药物代谢酶进行表型和基因型分析。它为UPCI研究者提供重要的咨询服务，包括药理学研究和药物测定、代谢和PK分析的设计。CPAF由梅里尔J. Egorin博士领导， 罗伯特·比斯博士的意见该设施由一个咨询委员会监督，该委员会代表医学院和药学院以及生物统计设施。在过去的一年中，CPAF为UPCI的29项临床试验，其他NCI指定癌症中心的14项CTEP赞助的临床试验以及54个动物药理学项目提供了支持。它还为3项体外药理学研究提供了分析化学支持。为了扩大其能力和增加其价值，CPAF大大增强了其分析化学仪器，PK建模软件和人员。该设施已经获得了两个LC/MS仪器和一个LC/MS/MS。CPAF被Pharsight Corporation认可为药代动力学卓越中心，从而使其能够实施复杂的软件。申请的CCSG资金将支持设施人员提供与检测开发、方法学、方案设计和数据解释相关的咨询服务，以及确保仪器和软件得到适当维护并可用于寻求设施支持的研究人员的项目。

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.