PEDIATRIC PHARMACOLOGY RESEARCH UNIT

本提案是一项竞争性更新申请，旨在响应RFA编号HD-98-002，继续资助密苏里州堪萨斯城儿童慈善医院（CMH）的儿科药理学研究部门，作为PPRU NICHD网络内的研究中心之一。 该单位的目标是：1）继续并扩大CMH PPRU在PPRU网络中的合作参与，主要目的是生成支持儿童药物标签的数据;和2）进行基础转化研究，重点是药物遗传学中的调节事件，个体发育的重要药物代谢酶和药效学，这将促进我们对药物处置和行动的年龄相关差异的理解。 具体目标包括：1）合作进行新药和目前上市的药物的研究，优先考虑PPRU网络研究; 2）识别、整理、分析和解释儿科临床试验的数据，这些数据足以扩展儿科标签; 3）使用分子方法来定义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界面; 5）提供一个独特的教学环境，其中儿科医生，医学专科医生，临床药师，护士和专职医疗人员可获得儿科临床药理学方面的专业知识。 研究者和申请机构实现这些目标和具体目标的能力表现在：1）有效的计划组成和管理; 2）申请机构内部的专业知识和资源; 3）与PPRU网络相关的先前和当前研究成果; 4）计划必要的项目扩展，以满足未来五年对儿科临床试验预期增加的需求;和5）提出两个新的研究建议，这些建议直接涉及计划目标，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.