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 关系的日益重视导致人们更加重视生成和分析此类数据，即使对于没有明确分子靶标的药物也是如此。人们对药物间相互作用以及药物代谢、处置和敏感性方面的药物遗传差异的认识不断增加，因此越来越需要通过测定来定义相关多态性及其临床影响。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) 提供最先进的药理学研究设施。 2002 年 9 月，CPAF 搬迁至希尔曼癌症中心研究馆内 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项目。服务包括药物、代谢物和其他材料的定量；代谢物的鉴定； 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 同工型和其他关键药物代谢酶进行表型和基因型分析。它为 UPCI 研究人员提供有关药理学研究设计以及药物测定、代谢和 PK 分析的重要咨询服务。 CPAF 由 Merrill J. Egorin 博士领导， 罗伯特·比斯博士的意见。该设施由代表医学院和药学院以及生物统计设施的咨询委员会监督。去年，CPAF 为 UPCI 的 29 项临床试验、CTEP 在其他 NCI 指定癌症中心资助的 14 项临床试验以及 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分析化学支持。为了扩展其能力并增加其价值，CPAF 大幅增强了其分析化学仪器、PK 建模软件和人员。该工厂购买了两台 LC/MS 仪器和一台 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。所请求的 CCSG 资金将支持设施人员努力提供与测定开发、方法、方案设计和数据解释相关的咨询服务，并努力确保仪器和软件得到适当维护并可供研究人员应用于项目。设施的支持。