Pediatric Pharmacology Research Unit

描述(由申请人提供)： 这项建议的总体目标是确保密歇根儿童医院和韦恩州立大学(WSU)的新生儿和儿科药理研究单位(PPRU)继续存在。密歇根儿童医院和韦恩州立大学(WSU)的PPRU进行了40多个多中心和单地点试验，并领导了对药物的评估，如关于静脉注射布洛芬的新配方的多中心替拉帕米，用于早期关闭早产儿的房间隔导管未闭。威斯康星州立大学PPRU位列学科招生前6名。此外，利用正电子发射计算机断层扫描对自闭症儿童5-羟色胺生物合成异常发育的研究，以及5-羟色胺代谢表型变异的鉴定，导致了丁螺环酮在自闭症药物治疗中的持续评估。NFkB在包括环氧合酶在内的炎症介质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，以产生关于生物利用度、配方、药物代谢、药代动力学、药效学、安全性和有效性的必要数据，这些新分子实体和药物目前正在使用，并可能用于未出生的胎儿、新生儿和儿童。2)确定GABA受体的个体发育，开发治疗新生儿呼吸暂停、新生儿缺氧缺血性脑病和自闭症等新生儿和儿童疾病的创新药物疗法3)应用纳米技术和树枝状大分子靶向给药，并开发调节发育期间跨血脑屏障药物转运的新制剂4)确定非侵入性哭声分析技术作为新生儿疼痛和非言语儿童替代药效学措施的有效性5)开发针对宫内发育迟缓胎儿的新型药物疗法。6)确定B2AR基因多态性在哮喘儿童β-肾上腺素能反应中的作用，为药物基因组学和蛋白质组学技术应用于儿童个体化药物治疗提供临床环境；7)提供儿童药理学方面的教育和培训。从整体上看，这些举措将促进胎儿、新生儿和儿童合理、安全、有效和具有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.