Pharmacokinetics

药代动力学

• 批准号: 8933331
• 负责人: DONALD L TRUMP
• 金额: $ 6.4万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-26 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8933331
• 关键词: Androgens; Antimetabolites; Biological; Biological Assay; Bone Marrow; Breast Cancer Prevention; Budgets; Cancer Center Support Grant; Chemoprevention; Clinical Research; Collaborations; Consultations; Core Biopsy; Data Analyses; Decision Making; Development; Doctor of Philosophy; Dose; Doxorubicin; Drug Combinations; Drug Kinetics; Effectiveness; Funding; Grant; Histone Deacetylase; Human Resources; Instruction; Lignans; National Comprehensive Cancer Network; Nicotine; PTK2 gene; Peer Review; Pharmaceutical Preparations; Pharmacodynamics; Phase; Plasma; Process; Prostatic Neoplasms; Publications; Qualifying; Reporting; Research; Research Personnel; Resource Sharing; Resources; Roswell Park Cancer Institute; Sampling; Schedule; Services; Taxane Compound; Topoisomerase; Topoisomerase Inhibitors; Toxic effect; Training; Translational Research; Tumor Tissue; Validation; base; chemotherapy; drug development; improved; inhibitor/antagonist; instrument; instrumentation; interest; liquid chromatography mass spectrometry; mTOR Inhibitor; mathematical model; meetings; member; method development; models and simulation; novel; pharmacodynamic model; programs; smoking cessation; taxane; treatment response

Under the direction of Gerald Fetterly, PhD (ET), the Pharmacokinetics/Pharmacodynamics (PK/PD) Shared Resource has grown significantly since the last CCSG grant renewal. Previously, the PK/PD Shared Resource had two divisions, which have now been consolidated to streamline processes and promote further integration and collaboration among investigators. The PK/PD Shared Resource has developed several new bioanalytical assays that support RPCI research efforts, including quantitation of drugs and biological species such as FAK inhibitors, topoisomerase inhibitors, antimetabolites, taxanes, doxorubicin, HDAC, TKl and mTOR inhibitors. These assays support ongoing investigator-initiated studies in five research programs (ET, CSBT, PS, GU, and Til). In addition, the Resource has bioanalytical assays to support chemoprevention studies, such as lignans for breast cancer prevention (PS), and nicotine and its metabolites to support smoking cessation (PS) projects. PK/PD staff utilize four state-of-the-art LC/MS/MS instruments, which detect eight androgens in plasma, bone marrow, and prostate tumor tissue at very low titers (GU). This has also improved the ability to detect topoisomerase in core biopsies (ET). Most recently, the Resource has developed a pharmacologically-driven mathematical PK/PD model to optimize anti-angiogenic treatment in AML, enhancing chemotherapy effectiveness. The Resource provides a complete service from methods development and validation to sample handling and analysis to PK/PD modeling and simulation, leading to informed decision-making about dosing, dose scheduling, and drug combinations. Data analysis using mathematical models to assess PK/PD relationships has led to presentations at national meetings, grant funding (i.e. ROl, NCCN, U01), and collaborative publications. The Shared Resource Director and/or other appropriate personnel provide initial consultation to users to discuss the scope of a project. Investigators are required to submit a sample submission form outlining what samples are being submitted to the Resource and what analyses are to be performed. Training is provided on an as-needed basis to qualified users who are interested in utilizing the Resource instrumentation. First priority for use is given to peer-review-funded RPCI CCSG members; second priority to non-peer-review- funded CCSG members; third priority to non-members and academic collaborators; and last priority to external users. During the reporting period, the PK/PD Shared Resource has served 17 members from 6 research programs, with 17% utilization by CCSG members with peer reviewed funding. The CCSG support provides 4% of the overall proposed budget.

在Gerald Fetterly，PhD（ET）的指导下，共享药代动力学/药效学（PK/PD） 自上次CCSG赠款续签以来，资源已大大增长。以前，PK/PD共享 资源有两个部门，现在已经合并以简化流程并进一步促进 研究人员之间的整合与协作。 PK/PD共享资源开发了几个新的 支持RPCI研究工作的生物分析测定，包括对药物和生物种类的定量 例如FAK抑制剂，拓扑异构酶抑制剂，抗代谢物，紫杉烷，阿霉素，HDAC，TKL和 mTOR抑制剂。这些分析支持正在进行的研究人员在五个研究计划中发动的研究（ET， CSBT，PS，GU和TIL）。此外，资源还具有生物分析测定以支持化学预防 研究，例如预防乳腺癌（PS）和尼古丁及其代谢物的研究 戒烟（PS）项目。 PK/PD员工使用四个最先进的LC/MS/MS Instruments，可检测 血浆，骨髓和前列腺肿瘤组织中的八个雄激素在非常低的滴度（GU）中。这也有 提高了检测核心活检（ET）中拓扑异构酶的能力。最近，资源有 开发了一种以药理为导向的数学PK/PD模型，以优化抗血管生成治疗 AML，提高化学疗法的有效性。资源提供了方法的完整服务 开发和验证对PK/PD建模和仿真进行样品处理和分析，导致 关于给药，剂量调度和药物组合的知情决策。数据分析使用 评估PK/PD关系的数学模型导致在国家会议上进行演讲，Grant 资金（即Rol，NCCN，U01）和合作出版物。 共享资源总监和/或其他适当的人员向用户提供初步咨询 讨论项目的范围。调查人员必须提交样本提交表格，概述什么 样本正在提交资源以及要执行的分析。提供培训 有兴趣利用资源仪器的合格用户的基础。 将使用的首要优先级用于同行评估资助的RPCI CCSG成员；非PER-REVIEW的第二个优先事项 - 资助的CCSG成员；非会员和学术合作者的第三优先事项；以及最后的优先事项 外部用户。在报告期间，PK/PD共享资源为17位成员提供了服务。 研究计划，CCSG成员使用同行审查的资金有17％的利用。 CCSG支持 提供总体预算的4％。