PEDIATRIC PHARMACOLOGY RESEARCH UNIT

该提案是对RFA编号HD-98-002的竞争续签申请，以继续资助密苏里州堪萨斯城儿童慈悲医院(CMH)的儿科药理学研究股，作为PPRU的NICHD网络内的站点之一。该股的目标是：1)继续并扩大CMH PPRU在PPRU网络中的合作参与，主要目的是产生支持儿童药物标签的数据；2)开展药物遗传学中的调控事件、重要药物代谢酶的个体发育和药效学方面的基础翻译研究，以促进我们对药物处置和作用的年龄相关差异的理解。具体目标包括：1)以PPRU网络研究为重点，合作开展新药和当前上市药物的研究；2)确定、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)使用分子方法确定儿童发育和药物代谢之间的“联系”；4)检查药物遗传学、关键药物代谢酶的个体发生和药物的药代动力学之间的接口；5)提供一个独特的教学环境，使儿科医生、医学专科专家、临床药剂师、护士和专职保健专业人员能够获得儿科临床药理学学科的专业知识。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：1)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；以及5)提出两项新的研究建议，这两项计划直接与计划目标有关，非常适合在PPRU网络内进行。

This proposal is a competing renewal application in response to RFA number HD-98-002 to continue funding of a Pediatric Pharmacology Research Unit at Children's Mercy Hospital (CMH), Kansas City, Missouri as one of the sites within the NICHD Network of PPRU's. The 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; and 2) To conduct basic translational research focusing on regulatory events in pharmacogenetics, ontogeny of important drug metabolizing enzymes and pharmacodynamics that will advance our understanding of age-related differences in drug disposition and action. 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 sufficient for expansion of pediatric labeling; 3) Use of molecular approaches to define the "link" between childhood development and drug metabolism; 4) Examination of the interface between pharmacogenetics, the ontogeny of critical drug-metabolizing enzymes, and the pharmacokinetics of drugs; 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 the discipline of pediatric clinical pharmacology. The capability of the investigators and applicant institution to accomplish these objectives and specific aims is demonstrated by: 1) 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 5) presentation of two new research proposals which speak directly to the program objectives and are ideally suited for conduct within the PPRU Network.