Pharmacokinetics Shared Resources Core

项目摘要/摘要-药代动力学共享资源 药代动力学共享资源(PKSR)是由SJCCC管理的共享资源，具有 使儿童能够更有效和更安全地使用抗癌药物的目标。我们通过促进实现这一目标 高质量、有竞争力的资助、同行评审的药代动力学(PK)和药效学(PD)研究 由从事临床试验和临床前癌症模型工作的SJCCC研究人员提供。PKSR与SJCCC合作 研究人员将最高质量的PK/PD研究整合到SJCCC临床前研究和I期，阶段 通过核心提供的集中研究基础设施进行第二阶段和第三阶段临床试验。PKSR还 通过提供PK/PD建模，支持其他机构的教育和研究工作的改进 研讨会和一个公众可用的、高访问量的在线资源来模拟血浆浓度 儿童使用甲氨蝶呤。在所有5个项目中，PKSR对癌症研究的影响都得到了证明 在影响较大的期刊上发表高水平的合作出版物和关键科学投稿，如 临床肿瘤学(n=12)、血液(n=11)、自然遗传学(n=4)和癌细胞(n=3)。在上一次资助期间 在此期间，2013年1月至2017年12月期间，139份SJCCC出版物使用了PKSR，占38份(27%) 方案间协作和96次(69%)方案内协作。这些出版物包括所有5个国家的出版物 方案：CCSP(n=6)、DBSTP(n=35)、HMP(n=86)、CBP(n=13)和NBTP(n=51)。在指数年期间 (2017财年)，使用PKSR的所有调查人员中有67%是SJCCC成员(56/83)。PKSR由Dr。 玛丽·雷林(HMP)，制药科学部主任，拥有32年以上的 具有儿科癌症PK、PD和药物基因组学研究经验。克里斯汀·克鲁斯博士是 PKSR，自2005年以来一直担任这一职务。她在临床领域有20多年的经验。 药理学、PK和药物遗传学。他们一起监督着一群技术人员，生物医学 完全融入临床研究和研究的模型师、协调员和研究护士 确保所有SJCCC临床PK/PD研究得到一致支持。 下一阶段的目标包括继续支持SJCCC PK/PD研究，以推进翻译 儿童抗癌药物的开发。服务将根据需要进行修改，以适应新的检测 技术和建模方法，并与SJCCC项目不断发展的需求保持一致。PKSR 还将继续与SJCCC调查人员合作，实施和支持临床方案 包括PK/PD研究。PKSR预计将实施12项新协议，并支持90名个人 在下一个项目期中每年的项目或协议。最后，PKSR将保持最先进的分析 设施，并在线带来新的分析技术和建模方法，以适应不断变化的需求 SJCCC项目。

PROJECT SUMMARY/ABSTRACT— Pharmacokinetics Shared Resource The Pharmacokinetic Shared Resource (PKSR) is an SJCCC-managed shared resource with the overarching goal of enabling more effective and safer anticancer drug use in children. We accomplish this goal by facilitating high-quality, competitively-funded, peer-reviewed pharmacokinetic (PK) and pharmacodynamic (PD) research by SJCCC investigators working in clinical trials and preclinical cancer models. PKSR collaborates with SJCCC investigators to integrate the highest-quality PK/PD studies into SJCCC preclinical research and Phase I, Phase II, and Phase III clinical trials via the centralized research infrastructure provided by the core. The PKSR also supports education and improvement of research efforts at other institutions by offering PK/PD modeling workshops and a publicly-available, highly-accessed online resource to simulate plasma concentrations of methotrexate in children. The impact of the PKSR on the cancer research in all 5 Programs is evidenced by the high level of collaborative publications and key scientific contributions in high-impact journals such as Journal of Clinical Oncology (n=12), Blood (n=11), Nature Genetics (n=4), and Cancer Cell (n=3). During the last funding period, 139 SJCCC publications from January 2013–December 2017 used the PKSR, representing 38 (27%) interprogrammatic and 96 (69%) intraprogrammatic collaborations. These included publications from all 5 Programs: CCSP (n=6), DBSTP (n=35), HMP (n=86), CBP (n=13), and NBTP (n=51). During the index year (FY2017), 67% of all investigators using the PKSR were SJCCC members (56/83). The PKSR is directed by Dr. Mary Relling (HMP), who is Chair of the Pharmaceutical Sciences Department and has more than 32 years of experience in pediatric cancer PK, PD, and pharmacogenomic research. Dr. Kristine Crews is the co-director of the PKSR, serving in this role since 2005. She has more than 20 years of experience in the areas of clinical pharmacology, PK, and pharmacogenetics. Together, they supervise a staff of technologists, biomedical modelers, coordinators, and research nurses who are fully integrated into the clinical research and pharmaceutical sciences enterprise to ensure that all SJCCC clinical PK/PD research is consistently supported. Goals for the next period include continuing to support SJCCC PK/PD research to advance the translational development of anticancer agents for children. Services will be modified, as needed, to accommodate new assay technologies and modeling approaches and to align with the evolving needs of the SJCCC Programs. The PKSR will also continue to collaborate with SJCCC investigators on the implementation and support of clinical protocols involving PK/PD studies. The PKSR anticipates implementing 12 new protocols and supporting 90 individual projects or protocols each year in the next project period. Lastly, the PKSR will maintain state-of-the art analytical facilities and bring online new assay technologies and modeling approaches to align with the evolving needs of the SJCCC Programs.