Pharmacokinetics

在杰拉尔德·费特利博士的指导下，药代动力学/药效学(PK/PD)共享 自上次CCSG授权续签以来，资源已显著增加。此前，PK/PD共享 人力资源司有两个司，现已合并，以精简程序和进一步促进 调查人员之间的整合和合作。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分析，包括药物和生物物种的量化 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五个研究项目(ET， CSBT、PS、GU和TIL)。此外，该资源还提供了支持化学预防的生物分析方法 研究，如预防乳腺癌(PS)的木脂素，以及尼古丁及其代谢物 戒烟(PS)项目。PK/PD工作人员使用四种最先进的LC/MS/MS仪器，它们检测到 血浆、骨髓和前列腺癌组织中8种雄激素的滴度非常低(GU)。这也已经 提高了检测核心活检(ET)中拓扑异构酶的能力。最近，该资源已经 开发了一个药物驱动的数学PK/PD模型来优化抗血管生成治疗 急性髓系白血病，增强化疗效果。该资源通过方法提供了完整的服务 从样品处理和分析到PK/PD建模和模拟的开发和验证，导致 有关剂量、剂量计划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全国会议上发表演讲， 资助(如ROL、NCCN、U01)和合作出版物。 共享资源总监和/或其他适当人员向用户提供初步咨询，以 讨论项目的范围。调查人员被要求提交一份样本提交表，概述什么 样品正在提交给资源，以及要进行哪些分析。培训在以下位置提供 为有兴趣利用资源工具的合格用户提供按需基础。 第一优先使用由同行审查资助的RPCCCSG成员；第二优先使用非同行审查-- 资助的CCSG成员；第三优先考虑非成员和学术合作者；最后优先考虑 外部用户。在本报告所述期间，PK/PD共享资源为6名成员中的17名成员提供了服务 研究项目，CCSG成员使用同行评审资金的利用率为17%。CCSG支持 提供总拟议预算的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.