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）的作用急剧增加。对PKJPD关系的进一步认识使得对生成和分析此类数据的重视程度增加，即使对于没有明确分子靶标的药物也是如此。对药物-药物相互作用和药物代谢、处置和易感性方面的药物-遗传差异的日益认识，增加了对测定相关多态性及其临床影响的需求。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。2002年9月，CPAF搬迁到希尔曼癌症中心研究馆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项目。服务包括药物、代谢物和其他物质的定量；代谢物鉴定；以及UPCI正在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分型。它为UPCI研究人员提供重要的咨询服务，包括药理学研究和药物分析、代谢和PK分析的设计。CPAF由Merrill J. Egorin博士领导，

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.