PEDIATRIC PHARMACOLOGY RESEARCH UNIT

辛辛那提儿童医院医学中心(CHMC)承诺提供基础设施和关键人员，这与建立儿科药理学研究单位(PPRU)的决心一致。目前参与药物临床试验的资源包括：1)NIH资助的临床研究中心(CRC)，2)临床试验管理计划，3)疫苗测试和治疗单位，4)持续的多中心参与，既来自CHMC(如儿科风湿病临床试验协调中心)，也来自网络(如儿童癌症小组、新生儿网络和母婴医学单位计划)，使对PPRU的承诺成为合乎逻辑的下一步。在CHMC设立PPRU的优势将是该机构在临床神经科学方面的专业知识，熟悉生物制药和基因疗法，在儿科专科的所有重要领域拥有广泛的杰出临床研究人员，以及获得每个年龄段和疾病类别的大量临床材料。 社区医疗中心PPRU将设在现有的儿童权利中心住院和门诊设施内，补充和丰富现有的儿童权利中心的能力和使用。CHMC PPRU将由儿童精神病学家/临床药理学家Sallee博士领导，他在临床试验的所有方面都有丰富的经验，并与制药业和FDA有现有的联系。CHMC在儿科药理学方面的专业知识可以从个人研究人员发起的项目和制药行业支持的项目的数量和呼吸中得到证明。在我们的PPRU核心教职员工中，我们在药物开发过程的所有方面都拥有专业知识，包括药物代谢的临床前研究(代谢物鉴定和同工酶特定的代谢途径)、药物在人体上的初始测试(I、II阶段)、药效学效果和替代标志物的综合评估、药代动力学评估以及安全性和有效性评估(II、III和IV阶段)以及药物相互作用(III、IV阶段)。CHMC PPRU将具有对研究对象进行细胞色素P450基因分型的重要能力。我们的两个网络提案证明了CHMC的PPRU的优势：JRA中重组人肿瘤坏死因子受体Fc融合蛋白的III期安全性、人群PK/疗效试验，以及轮状病毒疫苗安全性/有效性试验；以及两项评估钙通道阻滞剂(氨氯地平)预防环孢素A/他克莫司诱导的肾毒性的本地方案，以及一种新型非刺激性治疗ADHD的PK/PD研究(Tomoxetine)。

The Children's Hospital Medical Center (CHMC) in Cincinnati has made commitments of infrastructure and key personnel consistent with the resolve to establish a Pediatric Pharmacology Research Unit (PPRU). The confluence of resources now engaged in pharmaceutical clinical trials including: 1) an NIH-funded Clinical Research Center (CRC), 2) a Clinical Trials Administration Program, 3) a Vaccine Testing and Treatment Unit,4) ongoing multicenter participation both originating at CHMC (e.g Pediatric Rheumatology Clinical Trial Coordination Center), or as part of a network (e.g. Children's Cancer Group, Neonatal Network, and the Maternal-Fetal Medicine Unit program) make commitment to a PPRU a logical next step. Advantages of a PPRU at CHMC would be the institution's expertise in clinical neuroscience, a familiarity with biopharmaceutics and gene therapies, a breadth of distinguished Clinical Investigators in all important areas of Pediatric Subspecialty, and access to substantial clinical material in every age-group and disease category. The CHMC PPRU will be located within the existing CRC inpatient and outpatient facilities and will complement and enrich existing CRC capability and utilization. The CHMC PPRU will be Directed by Dr. Sallee, a child psychiatrist/clinical pharmacologist, with extensive experience in all aspects of clinical trials and with existing linkages to the pharmaceutical industry and the FDA. Expertise in pediatric pharmacology at CHMC is evidenced by the volume and breath of both individual investigator initiated and pharmaceutical industry supported projects. Within our PPRU core faculty we have expertise in all aspects of the drug development process, including preclinical investigation of drug metabolism (metabolite identification and isozyme-specific metabolic pathways), initial testing of drugs in humans (Phases I, II), comprehensive evaluation of pharmacodynamic effects and surrogate markers, pharmacokinetic evaluations, and assessments of safety and efficacy (Phases II, III, & IV) and drug interactions (Phases III, IV). The CHMC PPRU will have the important capability of performing cytochrome P450 genotyping on study subjects. Advantages of a PPRU at CHMC are documented by our two network proposals; a Phase III safety, population PK/efficacy trial of recombinant human tumor necrosis factor receptor Fc fusion protein in JRA, and a rotavirus vaccine safety/efficacy trial; and two local protocols which evaluate calcium channel blocker (Amlodipine) to prevent cyclosporin/tacrolimus induced nephrotoxicity as well as a PK/PD study of a novel non-stimulant treatment (Tomoxetine) for ADHD.