Pharmacologic Determinants for Optimized Therapy in HIV-Infected Children

描述(申请人提供)：我的长期职业目标是设计和执行儿科临床药物试验，重点了解传染病疗法的药理学，我通过这个以患者为导向的研究职业发展奖(K23)寻求对我职业发展的支持。随着我的儿科传染病研究金于2007年6月完成，这一职业发展计划将通过以下方式为我在儿科传染病和药理学之间的独立医生-科学家的职业道路提供必要的组成部分：(1)儿科药理学和临床试验设计的正式教育，包括药理学、药理学研讨会和期刊俱乐部的高级课程工作，负责研究行为的培训，以及加州大学圣地亚哥分校(UCSD)临床研究硕士学位，(2)人口药理学建模、模拟、UCSD的儿科药理研究单位(PPRU)和UCSD的国际母婴青少年艾滋病临床试验(IMPAACT)小组实验室的临床药理分析技术，以及(3)出版物、演示和指导监督的结构化计划。这一建议是可行的，因为有完善的职业发展和研究计划，以及我的导师、咨询委员会和加州大学圣迭戈分校儿科系的大力支持。尽管抗逆转录病毒药物在全球范围内用于感染艾滋病毒的儿童，但几乎没有药理学数据来确定目前的剂量方案是否最佳。在加州大学圣地亚哥分校PPRU主任Capparelli博士和UCSD母婴青少年艾滋病毒项目主任Spector博士的指导下，我将重点研究影响拉米夫定、齐多夫定的药代动力学和药效学的药理学决定因素，以及艾滋病毒感染儿童的诊断。通过模拟这一建议中开发的人口模型的影响，我们将确定当前的给药方案是否提供最佳的血浆浓度。这些数据对全球儿童的健康非常重要，因为我们的数据将提供有关儿童抗逆转录病毒药物的新的、关键的药理学信息，并确保当前的指南为各个年龄段的艾滋病毒感染儿童提供最佳剂量。

DESCRIPTION (provided by applicant): With a long-term career goal of designing and executing pediatric clinical drug trials focused on understanding the pharmacology of infectious disease therapies, I seek support in my career development through this Mentored Patient-Oriented Research Career Development Award (K23). With the completion of my Pediatric Infectious Diseases fellowship in June 2007, this career development plan will provide me with the necessary components for an independent physician-scientist career path at the interface between pediatric infectious diseases and pharmacology via the following: (1) formal education in pediatric pharmacology and clinical trials design, including advanced coursework in pharmacology, pharmacology seminars and journal clubs, training in the responsible conduct of research, and a Masters degree in Clinical Research at the University of California, San Diego (UCSD), (2) research training in population pharmacologic modeling, simulation, and clinical pharmacology analysis techniques at UCSD's Pediatric Pharmacology Research Unit (PPRU) and UCSD's International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group laboratory, and (3) a structured plan for publications, presentations, and mentoring oversight. This proposal is feasible because of the sound career development and research plans as well as the strong support from my mentors, advisory committee, and the Department of Pediatrics at UCSD. Despite the worldwide use of antiretrovirals in HIV-infected children, little pharmacologic data exists to determine whether the current dosing regimens are optimal. Under the guidance of Dr. Capparelli, Director of UCSD's PPRU and Dr. Spector, Director of UCSD's Mother Child Adolescent HIV Program, I will focus my research on the pharmacologic determinants that affect the pharmacokinetics and pharmacodynamics of lamivudine, zidovudine, and diagnosing in HIV-infected children. By simulating the effects of the population models developed in this proposal, we will determine whether the current dosing regimens provide optimal plasma concentrations. These data are important for the health of children worldwide as our data will provide novel, critical pharmacologic information about antiretrovirals in children and ensure that current guidelines provide optimal dosing for HIV-infected children across a wide age range.