Pediatric Pharmacology Research Unit

描述（由申请人提供）： 本提案的总体目标是确保密歇根州儿童医院和韦恩州立大学（WSU）的新生儿和儿科药理学研究单位（PPRU）的延续华盛顿州立大学PPRU已经进行了40多项多中心和单中心试验，并领导了药物的评价，如多中心替拉尔对静脉布洛芬新制剂的评价，用于早期关闭动脉导管未闭。早产儿WSU PPRU在受试者入组方面位列前6名。此外，使用PET扫描和5-羟色胺代谢的表型变体的鉴定对自闭症儿童中5-羟色胺生物合成的异常发展进行的研究导致了丁螺环酮在自闭症药物治疗中的持续评估。NFKb在包括环加氧酶在内的炎症介质的基因表达中的作用的证明确定了药物干预的靶点。具体目标包括：1）进行研究，以生成关于目前使用和可能用于未出生胎儿、新生儿和儿童的新分子实体和药物的生物利用度、制剂、药物代谢、药代动力学、药效学、安全性和有效性的必要数据。2)为了确定GABA受体的个体发育，并开发新生儿和儿童疾病（如新生儿呼吸暂停）的创新药物疗法，新生儿缺氧缺血性脑病和自闭症3）应用纳米技术和树枝状聚合物在靶向药物递送中的使用，并开发新的制剂以调节药物在发育过程中穿过血脑屏障的转移4）确定非侵入性哭声分析技术作为新生儿疼痛和无语言儿童替代药效学测量5）开发用于宫内生长迟缓胎儿的新药物疗法。6）确定B2 AR基因多态性在哮喘儿童β肾上腺素能反应中的作用，并为药物基因组学和蛋白质组学技术的应用提供临床环境，从而导致个体化的儿科药物治疗; 7）提供儿科药理学的教育和培训计划。总的来说，这些举措将促进胎儿，新生儿和儿童的合理，安全，有效和成本效益的药物治疗。

DESCRIPTION (provided by applicant): The overarching aim of this proposal is to ensure continuation of the Neonatal and Pediatric Pharmacology Research Unit (PPRU) at the Children's Hospital of Michigan and Wayne State University (WSU) The WSU PPRU has conducted more than 40 multicenter and single site trials and has led the evaluation of drugs such as the multicenter tiral on the new formulation of intravenous ibuprofen for early closure of patent ductus artriousus in the preterm newborn. WSU PPRU ranked among the top 6 sites for subject enrollment. In addition, studies on aberrant development of serotonin biosynthesis in autistic children using PET scanning and identification of the phenotypic variants of serotonin metabolism have led to the ongoing evaluation of buspirone in drug therapy of autism. The demonstration of the role of NFKb in the gene expression of inflammatory mediators including the cyclo-oxygenases identified a target focus for drug intervention. The specific aims include: 1) the conduct of studies to generate requisite data on bioavailability, formulations, drug metabolism, pharmacokinetics, pharmacodynamics, safety, and effectiveness of new molecular entities and drugs currently used and are potentially used in the unborn fetus, newborn and children. 2) To determine the ontogeny of GABA receptors and to develop innovative pharmacotherapies of neonatal and childhood diseases such as neonatal apnea, neonatal hypoxic-ischemic encephalopathy and autism 3) To apply nanotechnology and use of dendrimers in targeted drug delivery and to develop novel formulations to modulate drug transfer across the blood brain barrier during development 4) to determine the validity of non-invasive cry analyses technique as surrogate pharmacodynamic measure in neonatal pain and non-verbal children 5) to develop novel drug therapies for fetuses with intrauterine growth retardation. 6)To determine the role of B2AR gene polymorphism in beta adrenergic response in asthmatic children and to provide a clinical milieu for the application of pharmacogenomics and proteomic technology leading to individualized pediatric pharmacotherapy and 7) to provide educational and training programs in pediatric pharmacology. Taken collectively, these initiatives will advance rational, safe, effective and cost beneficial drug therapies in the fetus, newborn and children.