CLINICAL PHARMACOOOGY ANALYTICAL FACILITY

作为抗癌药物，药代动力学(PK)和药效学(PD)的作用已显著增强 药物发现和开发已转向分子靶向治疗。增加了 对PK/PD关系的认识导致更加重视生成和分析这样的关系 数据，即使对于没有确定分子目标的试剂也是如此。对药物-药物相互作用的认识 药物代谢、处置和敏感性的药物遗传学差异增加了对 检测以确定相关的多态性及其临床影响。临床药理分析 中国药学研究所(CPAF)成立于1994年，旨在为 匹兹堡大学癌症研究所(UPCI)。CPAF占地1000平方英尺的实验室空间 在希尔曼癌症中心的研究展馆里。CPAF支持多种UPCICCSG程序 除了广泛的UPCI临床前和临床药理学研究活动外，分子 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；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，如人类 肝细胞培养和亚细胞组分，如微粒体和胞浆，以表征 细胞色素P450亚型和其他负责生产的关键药物代谢酶 确定了代谢物。CPAF为UPCI调查人员提供重要的咨询服务 设计药理研究和药物分析、代谢和PK分析。CPAF是联合导演的 由Merrill J.Egorin博士和Jan H.Beumer博士撰写，并由代表 医学院和药学学院，以及生物统计机构。在过去的6年里，CPAF 为UPCI21项癌症治疗评估计划(CTEP)赞助的临床试验提供支持，10 UPCI的研究人员发起的临床试验，CTEP赞助的其他NCI指定的28项临床试验 癌症中心或合作小组，以及35个动物药理学项目。它还提供了分析 为3项体外药理学研究提供化学支持。为了扩展其功能并增加其价值， CPAF大幅增强了其分析化学仪器、PK建模软件和 人事部。自上一次竞争性续签UPCI癌症中心支持赠款以来，该机构已经 另外购置了2台LC-MS仪器和2台LC-MS/MS仪器。也是自上一次比赛以来 续签后，CPAF成功竞争成为中国药理学核心实验室 妇科肿瘤组，并成功地重新竞争其作为药理学核心的角色 癌症和白血病B组CPAF继续是加州大学的主要合作者 南加州生物医学模拟资源，从而允许CPAF实施 完善的PK和PD建模软件。CCSG申请的资金将支持设施人员 为他们在提供与分析开发、方法、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地 维护并可供寻求该机制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 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.