Pharmacokinetics

在Gerald Fetterly，PhD（ET）的指导下，药代动力学/药效学（PK/PD）共享 自上次CCSG赠款更新以来，资源大幅增长。之前，PK/PD共享 资源部有两个司，现已合并，以简化流程，进一步促进 调查人员之间的整合和协作。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，包括药物和生物物种的定量 如FAK抑制剂、拓扑异构酶抑制剂、抗代谢物、紫杉烷、阿霉素、HDAC、TK 1和 mTOR抑制剂。这些测定支持正在进行的五个研究项目（ET， CSBT、PS、GU和Til）。此外，该资源还具有支持化学预防的生物分析测定 研究，如木脂素用于预防乳腺癌（PS），尼古丁及其代谢物，以支持 戒烟（PS）项目。PK/PD工作人员使用四种最先进的LC/MS/MS仪器， 血浆、骨髓和前列腺肿瘤组织中的8种雄激素的滴度非常低（GU）。这也 提高了在核心活检（ET）中检测拓扑异构酶的能力。最近，资源 开发了一种药理学驱动的数学PK/PD模型，以优化抗血管生成治疗， AML，增强化疗效果。资源提供了一个完整的服务， 从样品处理和分析到PK/PD建模和模拟的开发和验证， 关于给药、剂量安排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发表演讲， 资助（即RO 1、NCCN、U 01）和合作出版物。 共享资源主管和/或其他适当人员向用户提供初步咨询， 讨论项目的范围。要求研究者提交一份样本提交表，概述 样品提交给资源部门，以及需要进行哪些分析。培训内容包括 向有兴趣使用资源工具的合格用户提供按需基础。 第一优先权给予同行评审资助的RPCI CCSG成员;第二优先权给予非同行评审成员- 受资助的CCSG成员;第三优先于非成员和学术合作者;最后优先于 外部用户。在本报告期内，PK/PD共享资源已为来自6个国家的17名成员提供了服务。 研究计划，CCSG成员利用同行评审资金的利用率为17%。CCSG支持 占总预算的4%。

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.