Children's Center for Clinical Pharmacology Studies

描述(由申请人提供)： 本提案是对RFA#HD-01-003的回应，目的是继续资助密苏里州堪萨斯城儿童慈悲医院和诊所(CMH)的儿科药理研究股，作为PPRU NICHD网络内的站点之一。该股的总体目标是：1)继续并扩大CMH PPRU在PPRU网络中的合作参与，主要目的是产生数据，通过创造新的信息和知识支持儿童药物标签；2)开展发展药理学的基础研究和转化研究，这将促进我们对药物处置和作用(包括有益和不利的)的遗传、年龄和疾病相关差异的影响的理解。具体目标包括：1)合作进行新药和当前上市药物的研究，优先考虑PPRU网络研究；2)识别、整理、分析和解释足以扩大儿科标签的儿科临床试验数据；3)使用分子方法定义儿童发育、疾病表现、药物生物转化和药物作用之间的“联系”；4)使用生物信息学、药物基因组学、代谢组学来探索和确定重要药物代谢酶和转运体的发育调节基础；5)提供独特的教学环境，让儿科医生、医学专科医生、临床药剂师、护士和专职医护人员在临床调查和儿科临床药理学学科方面获得专业知识。研究人员和申请机构实现这些目标和具体目标的能力体现在：i)有效的计划组成和管理；2)申请机构内的专业知识和资源；3)与PPRU网络有关的以往和目前的研究成就；4)预计的计划扩展，以满足未来五年对儿科临床试验的预期增加的需求，并加强将转化科学纳入药物开发过程；以及5)提出两项新的研究建议，这两项建议直接与计划目标有关，非常适合作为PPRU网络的一部分进行。

DESCRIPTION (provided by applicant): This proposal is a sent in response to RFA #HD-01-003 to continue funding of a Pediatric Pharmacology Research Unit at Children's Mercy Hospitals and Clinics (CMH) in Kansas City, Missouri as one of the sites within the NICHD Network of PPRU's. The overall objectives of the Unit are: 1) to continue and expand collaborative participation of the CMH PPRU in the PPRU Network for the primary purpose of producing data that will support labeling of drugs for children through the creation of new information and knowledge; and 2) To conduct basic and translational research in developmental pharmacology that will advance our understanding of the impact of genetic- age- and disease-related differences in drug disposition and action (both beneficial and adverse). Specific Aims include: 1) The collaborative conduct of studies of new and currently marketed drugs with priority given to PPRU Network studies; 2) The identification, collation, analysis, and interpretation of data from pediatric clinical trials that are sufficient for expansion of pediatric labeling; 3) Use of molecular approaches to define the "link" between childhood development, disease expression, drug biotransformation and drug action; 4) Use of bioinformatics, pharmacogenomics, metabolomics to explore and define the basis of developmental regulation of important drug metabolizing enzymes and transporters; 5) The provision of a unique teaching environment in which pediatricians, medical sub-specialists, clinical pharmacists, nurses and allied health care professionals can gain expertise in clinical investigation and the discipline of pediatric clinical pharmacology. The capability of the investigators and applicant institution to accomplish these objectives and specific aims is demonstrated by: I) effective programmatic composition and administration; 2) expertise and resources within the applicant institution; 3) previous and current research accomplishments related to the PPRU Network; 4) projected programmatic expansion necessary to meet the anticipated increased demands for pediatric clinical trials over the next five years and also, to enhance the integration of translational science into the drug development process; and 5) presentation of two new research proposals which speak directly to the program objectives and are ideally suited for conduct as part of the PPRU Network.