PEDIATRIC PHARMACOLOGY RESEARCH UNIT

该提案是一份竞争性的更新申请，以响应RFA号HD-98-002，继续资助密苏里州堪萨斯城儿童慈善医院（CMH）的儿科药理学研究单位，作为PPRU的NICHD网络中的一个站点。该股的目标是：1)继续和扩大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、重要药物代谢酶的个体发生和药效学方面的调控事件的基础转化研究，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)合作开展新药和当前上市药物的研究，优先考虑PPRU网络研究；2)鉴别、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)利用分子方法确定儿童发育与药物代谢之间的“联系”；4)研究药物遗传学、关键药物代谢酶的个体发生和药物的药代动力学之间的联系；5)提供一个独特的教学环境，使儿科医生、医学专科医生、临床药师、护士和专职卫生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表现在：1)有效的方案组成和管理；2)申请机构内部的专业知识和资源；3)与PPRU网络相关的过去和现在的研究成果；4)为满足未来5年儿科临床试验预期增长的需求，预计的项目扩展是必要的；5)提出两项新的研究建议，这些建议直接涉及项目目标，并且非常适合在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.