Center for Pediatric Clinical Pharmacology Research

描述(由申请人提供)： 本提案是对RFA HD-03-O01的回应，目的是获得对肯塔基州路易斯维尔KCPCRU的支持，作为NICHD PPRU网络中的一个站点。这项提议的长期计划目标是：1)扩大KCPCRU积极参与多中心合作临床试验，目的是产生高质量的科学和临床数据，以支持新生儿、婴儿和儿童的新的、目前市场上的和非专利的药物的适龄标签2)进一步发展路易斯维尔大学致力于进行翻译研究的基础和临床科学家的互动网络，重点是表征人类发育对儿童的生物目标、关键致病介质和生理替代物的影响3)通过发展多学科培训计划，医生完成教育使命，药剂师和护士可以获得儿科临床药理学方面的专业知识。这些目标将通过以下具体目标来实现：1)在PPRU网络、NICI-ID、美国国立卫生研究院和FDA内设计和进行关于早产儿和足月儿、婴儿、儿童和青少年的新的、目前上市的和非专利的药理学药物的药代动力学、药效学、安全性和有效性的协作临床试验2)优先考虑PPRU网络研究2)开发一个独立的L蛋白质组实验室的“微型核心”，作为网络赞助试验的补充资源，并支持新的蛋白质组技术在儿科药理学研究中的应用3)应用蛋白质组技术来识别、开发、验证和/或推断成人对诊断、预后、疗效、毒性和疾病活动性的生物标记物的研究4)描述发育、疾病和遗传学对儿童药理反应的生物靶点、关键致病介质和生理替代物的影响5)通过提供包括临床服务、研究和授课在内的多方面培训经验，促进儿科临床药理学学科的学生、住院医师、研究员和初级教员的发展。研究人员和申请机构能够实现这些目标的基础是：1)支持我们计划的临床和实验室研究部分的优秀基础设施2)儿科临床药理学研究的临床和基础科学方面的集体专业知识3)过去和目前的研究成就，包括与PPRU现有网络站点合作调查的成果4)基础和临床研究科学家的多学科协作网络的存在，致力于在儿童进行临床药理学研究5)提出4项与计划目标直接相关的新研究建议，这些建议非常适合在PPRU网络内进行。

DESCRIPTION (provided by applicant): This proposal is submitted in response to RFA HD-O3-O01 to obtain support for the KCPCRU, Louisville, KY, as a sites in the NICHD PPRU Network. Long-term proqrammatic objectives of this proposal are: 1) To expand the active participation of the KCPCRU in multi-centered collaborative Clinical trials for the purpose of generating high-quality scientIfic and clinical data to support age-appropriate labeling of new, currently marketed and off-patent pharmacologic agents in newborns, infants and children 2) To further develop the interactive network of basic and clinical scientists at the University of Louisville dedicated to conducting translational research with a focus on characterizing the effect of human development on biologic targets, key pathogenic mediators and physiologic surrogates of pharmacologic response in children 3) To fulfill the educational mission through the development of a multi-disciplinary training program in which physicians, pharmacists and nurses can gain expertise in Pediatric Clinical Pharmacology. These objectives will be accomplished by the following specific aims: 1) To design and conduct collaborative clinical trials within the PPRU network, NICI-ID, NIH and FDA regarding pharmacokinetics, pharmacodynamics, safety, and efficacy of new, currently marketed and off-patent pharmacologic agents in preterm and term newborns, infants, children and adolescents Priority will be given to PPRU network studies 2) To develop an independent "mini-core" of the U of L Proteomics Laboratory that will serve as a complementary resource for network-sponsored trials and support the application of novel proteomic techniques in pediatric pharmacology studies 3) To apply proteomic techniques to identify, develop, validate andlor extrapolate from adult studies on biomarkers of diagnosis, prognosis, efficacy, toxicity and disease activity 4) To characterize the effects of development, disease and genetics on biologic targets, key pathogenic mediators and physiologic surrogates of pharmacologic response in children using a translational science approach 5) To promote the development of students, residents, fellows and junior faculty in the discipline of Pediatric Clinical Pharmacology by providing a multi-faceted training experience encompassing clinical service, research and didactic lectureship. The investigators and applicant institution are caoable of achieving these aims based upon: 1 )an excellent infrastructure to support the clinical and laboratory research components of our program 2)collective expertise in clinical and basic science aspects of pediatric clinical pharmacology research 3)previous and current research accomplishments including those resulting from collaborative investigations with existing PPRU network sites 4) the presence of a multi-disciplinary collaborative network of basic and clinical research scientists dedicated to the conduct of clinical pharmacology studies in children 5)presentation of 4 novel research proposals that speak directly to the program objectives and that are ideally suited for conduct within the PPRU network.