Developmental and Translational Pharmacology of Pediatric Antimicrobial Therapy

描述（由申请人提供）：本项目题为“儿科抗菌治疗的发育和转化药理学”，作为响应RFA-HD-10-026：儿科发育药理学（RPDP）项目（U 54）研究专门中心的申请提交。在加州大学圣地亚哥分校拟议计划的总体主题是汇集发育生理学，药理学和传染病领域的非临床和临床专家，并进行转化研究，以推进儿科发育药理学领域。该计划包括3个主要项目; 2个试点项目和4个核心项目。三个主要项目是“婴儿和儿童的多粘菌素E甲磺酸盐剂量优化”、“药用抗生素和内源性抗生素之间的药物相互作用”和“ 氨苄青霉素肾清除率”。每个项目都使用管理核心（A）、药理学核心（B）、定量药理学测定核心（C）以及培训和推广核心（D）。这些项目和核心的共同努力将表征抗菌治疗的处置和潜在毒性的发展变化。该计划将利用在圣地亚哥加州大学基础科学实验室的发现，并在非临床和临床领域扩展这些研究。核心将开发适用于儿科年龄段的药理学测定，并利用创新的建模和模拟技术来优化这些项目产生的知识，并帮助建立临床和非临床发现之间的联系。这些项目和核心活动将为未来的儿科药理学家提供丰富的培训环境。而 该RPDP计划的重点是解决与抗菌治疗有关的发育药理学问题，了解大鼠和人类燕麦转运蛋白成熟的决定因素对其他类型的药物通过肾脏排泄具有广泛的意义。 公共卫生相关性：由于宿主防御不成熟，对现有抗生素的耐药性增加以及药物分布，代谢和消除的发育变化，有效的抗菌治疗在婴幼儿中仍然具有挑战性。该课程将增加对发育药理学和宿主与抗菌治疗相互作用的机械理解。

DESCRIPTION (provided by applicant): This program, entitled "Developmental and Translational Pharmacology of Pediatric Antimicrobial Therapy", is submitted as an application responsive to RFA-HD-10-026: Specialized Center in Research in Pediatric Developmental Pharmacology (RPDP) Program (U54). The overall theme of the proposed program at the UC San Diego is to bring together non-clinical and clinical experts in the fields of developmental physiology, pharmacology, and infectious diseases and conduct translational research to advance the field of pediatric developmental pharmacology. This program is comprised of 3 Main Projects; 2 Pilot Projects and 4 Cores. The three main projects are "Colistimethate Dose Optimization in Infants and Children", "Drug-Drug Interactions between Pharmaceutical and Endogenous Antibiotics" and "Developmental Aspects of Aminopenicillin Renal Clearance". Each project utilizes the Administrative Core (A), the Pharmacometrics Core (B), the Quantitative Pharmacology Assay Core (C) and the Training and Outreach Core (D). Working together these projects and cores will characterize developmental changes in the disposition and potential toxicity of antimicrobial therapy. The program will capitalize on the discoveries made in basic science laboratories at UC Diego and extend these investigations in both non-clinical and clinical domains. The Cores will develop pharmacologic assays that are appropriate across the pediatric age continuum and utilize innovative modeling and simulation techniques to optimize the knowledge generated from these projects and help establish links between clinical and non-clinical findings. These projects and core activities will provide a rich training environment for future pediatric pharmacologist. While this RPDP program is focused to address developmental pharmacologic issues relating to antimicrobial therapy, understanding the determinants of Oat transporter maturation in both rat and humans has broad Implications for other classes of drugs undergoing renal excretion. PUBLIC HEALTH RELEVANCE: Effective antimicrobial therapy remains challenging in infants and young children due to immaturity in host defenses, increasing resistance to existing antibiotics and developmental changes in drug distribution, metabolism and elimination. This program will increase mechanistic understanding of developmental pharmacology and host Interactions with antimicrobial therapy.