CLINICAL PHARMACOOOGY ANALYTICAL FACILITY

临床药学分析设施

• 批准号: 8519335
• 负责人: Jan Hendrik Beumer
• 金额: $ 10.82万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8519335
• 关键词: AA Spectrophotometry; Advisory Committees; Analytical Chemistry; Animals; Antineoplastic Agents; Biological; Biological Assay; Biometry; California; Cancer Center; Cancer Center Support Grant; Cancer Therapy Evaluation Program; Cancer and Leukemia Group B; Chemicals; Clinical; Clinical Pharmacology; Clinical Trials; Computer software; Consultations; Cytochrome P450; Cytosol; Data; Data Analyses; Detection; Development; Drug Interactions; Drug Kinetics; Ensure; Enzymes; Fluorescence; Funding; Genetic Polymorphism; Goals; Guidelines; Gynecologic Oncology Group; Hepatocyte; High Pressure Liquid Chromatography; Human; Human Resources; In Vitro; Instruction; Laboratories; Metabolism; Methodology; Methods; Microsomes; Molecular; Molecular Target; NCI-Designated Cancer Center; Pharmaceutical Preparations; Pharmacodynamics; Pharmacogenetics; Pharmacology; Pharmacy facility; Predisposition; Productivity; Protein Isoforms; Protocols documentation; Research; Research Activity; Research Design; Research Personnel; Resources; Role; Sampling; Services; Subcellular Fractions; System; Therapeutic; Universities; University of Pittsburgh Cancer Institute; Validation; assay development; design; drug development; drug discovery; drug metabolism; instrument; instrumentation; liquid chromatography mass spectrometry; medical schools; meetings; novel; pharmacodynamic model; pharmacokinetic model; pre-clinical; programs; research clinical testing; research facility; simulation; square foot

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.

药物动力学（PK）和药效学（PD）的作用随着抗癌药物的发展而急剧增加。 药物发现和开发已经转向分子靶向治疗。增加 对PK/PD关系的认识导致更加重视生成和分析这些 数据，即使对于没有定义的分子靶点的试剂。药物相互作用的认识， 药物代谢、处置和易感性的药物遗传学差异增加了对 确定相关多态性及其临床影响的试验。临床药理分析 中国药理研究中心（CPAF）成立于1994年，旨在为中国药理学研究中心提供最先进的药理学研究设施。 匹兹堡大学癌症研究所（UPCI）。CPAF占地1,000平方英尺的实验室空间 在希尔曼癌症中心的研究馆CPAF支持许多UPCI CCSG程序 除了广泛的UPCI临床前和临床药理学研究活动，分子 治疗学和药物发现计划。服务包括药物、代谢物和其他 材料;代谢物鉴定;以及抗癌药物的PK和PD分析， UPCI的临床前和/或临床评价。CPAF还使用体外方法，如人 肝细胞培养物和亚细胞级分，如微粒体和胞质溶胶，以表征 细胞色素P450亚型和其他负责产生 代谢物鉴定。CPAF为UPCI调查人员提供重要的咨询服务， 药理学研究和药物测定、代谢和PK分析的设计。CPAF是共同指导的 作者：梅里尔·J·埃戈林和扬·H. Beumer，并由一个代表 医学院和药学院，以及生物统计设施。在过去的六年里，CPAF 为UPCI的21项癌症治疗评估计划（CTEP）赞助的临床试验提供支持，10 在UPCI进行的由制药商发起的临床试验，在其他NCI-designated 癌症中心或合作团体，以及35个动物药理学项目。它还提供了分析 3项体外药理学研究的化学支持。为了扩展其功能并增加其价值， CPAF大大增强了其分析化学仪器、PK建模软件和 人员的自上次竞争性更新UPCI癌症中心支持补助金以来，该机构已 另外购置了2台LC-MS仪器和2台LC-MS/MS仪器。此外，自上一次竞争性 更新后，CPAF成功地竞争成为药理学核心实验室， 妇科肿瘤学小组并成功重新竞争其作为药理学核心的角色 癌症和白血病组B。CPAF仍然是牛津大学的主要合作伙伴 南加州生物医学模拟资源，从而使CPAF能够实施 复杂的PK和PD建模软件。所要求的CCSG资金将支持设施人员 为他们在提供与分析开发、方法学、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 维持并可供寻求基金支助的调查人员应用于项目。