Cancer Pharmacokinetics and Pharmacodynamics Facility

摘要：肿瘤药代动力学和药效学实验装置 UPCI癌症药代动力学和药效学机构(CPPF)因其 在开发和提供研究试剂的PK分析方面表现出色。此外，在过去 授权期内，共享资源为开发和验证新的药效学奠定了基础 (PD)确认目标参与并确定范围、持续时间和关系的方法 毒性和/或活动性的临床相关结果。CPPF的活动是基于最先进的量化 (根据FDA方法验证指南进行分析)和定性质谱学技术 用于表征药物靶标的小分子(PK)及定量和半定量分析 例如酶联免疫吸附试验(ELISA)、免疫印迹、免疫组织化学(IHC)和 定量核酸扩增(QPCR)。CPPF的具体目标是：1)提供无障碍、 经济、全面和最先进的分析化学和药代动力学(PK)服务 支持基础和临床UPCI研究项目；以及2)提供综合药效学(PD) 为翻译和临床UPCI研究项目提供支持的服务。与科学家和 临床医生，CPPF(1)为临床前/临床方案提交提供行政支持，(2) 协调高质量处理前和处理后生物样本的获取和储存，(3)确定 并对生物样品中的药物、代谢物和其他化学成分进行定量，(4)测量 血清/血浆细胞因子和生长因子，(5)估计细胞内蛋白表达(在PBMC，肿瘤， 皮肤)通过用于生物标记物开发的各种技术，(6)协助开发新的检测 (7)分析了协议中PK-PD的关系。该设施 维护并继续扩展各种分析化学仪器，这些仪器在 检验实施和验证的公认实践标准和FDA指南。联席董事 关键人员在PK/PD分析方面有超过50年的经验。提供的服务包括 旨在补充病理学、免疫学和分析药理学方面的现有共享资源 最终目标是推进临床/转化性研究。在当前项目期内 来自所有10个UPCI研究项目的调查人员都使用了CPPF。

Abstract: Cancer Pharmacokinetics and Pharmacodynamics Facility (CPPF) The UPCI Cancer Pharmacokinetics and Pharmacodynamics Facility (CPPF) is nationally recognized for its excellence in developing and delivering PK analyses of investigational agents. Furthermore, during the past grant period the shared resource has built the infrastructure to develop and validate novel pharmacodynamics (PD) methodology to confirm target engagement and determine the extent, duration, and relationship with clinically relevant outcomes of toxicity and/or activity. CPPF activities are based on state-of-the-art quantitative (assays according to FDA guidance for method validation) and qualitative mass spectrometric technologies for small molecules (PK) and quantitative and semi-quantitative analysis for characterization of drug targets (PD) such as enzyme-linked immunosorbent assays (ELISA), immunoblotting, immunohistochemistry (IHC), and quantitative nucleic acid amplification (qPCR). The specific aims of CPPF are to: 1) provide accessible, economical, comprehensive, and state-of-the-art analytical chemical and pharmacokinetic (PK) services in support of basic and clinical UPCI research programs; and 2) provide integrated pharmacodynamic (PD) services in support of translational and clinical UPCI research programs . Working with scientists and clinicians, CPPF (1) provides administrative support for preclinical/clinical protocol submissions, (2) coordinates acquisition and banking of high quality pre-and post-treatment biological samples, (3) identifies and quantitates drugs, metabolites, and other chemical moieties in biological samples, (4) measures serum/plasma cytokines and growth factors, (5) estimates intracellular protein expression (in PBMC, tumor, skin) by various techniques for biomarker development, (6) assists in development of novel detection methodologies for PK and PD, and (7) analyzes the PK-PD relationship within the protocol. The Facility maintains, and continues to expand, a diverse array of analytical chemistry instrumentation operated under accepted practice standards and FDA guidelines for assay implementation and validation. The Co-Directors and key personnel have a combined experience of over 50 years in PK/PD analysis. The provided services are designed to complement existing shared resources in pathology, immunology, and analytical pharmacology with the ultimate goal of advancing clinical/translational research. During the current project period investigators from all 10 UPCI Research Programs used the CPPF.