Pharmacologic Determinants for Optimized Therapy in HIV-Infected Children

HIV 感染儿童优化治疗的药理学决定因素

• 批准号: 7490096
• 负责人: ADRIANA H TREMOULET
• 金额: $ 12.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490096
• 关键词: Accounting; Adherence; Adolescent; Advisory Committees; Affect; Age; CD4 Lymphocyte Count; California; Child; Child health care; Childhood; Clinic; Clinical; Clinical Pharmacology; Clinical Research; Clinical Trials; Clinical Trials Design; Communicable Diseases; Computer software; Data; Development; Development Plans; Diagnosis; Didanosine; Disease model; Dose; Drug Exposure; Drug Kinetics; Education; Ensure; Ethnic Origin; Evaluation; Fellowship; Gender; Goals; Guidelines; HIV; Highly Active Antiretroviral Therapy; International Maternal Pediatric Adolescent AIDS Clinical Trials Group; Journals; Laboratories; Lamivudine; Lamivudine/Zidovudine; Lead; Learning; Master' s Degree; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Mexico; Minimum Inhibitory Concentration measurement; Modeling; Mothers; Multivariate Analysis; Outcome; Pediatrics; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Physicians; Plasma; Population; Process; Publications; RNA; Race; Range; Recommendation; Recruitment Activity; Renal function; Research; Research Training; Resistance development; Resources; Scientist; Simulate; Structure; Techniques; Time; TimeLine; Training; Treatment Protocols; Universities; Use of New Techniques; Validation; Variant; Viral; Weight; antiretroviral therapy; base; career; clinical effect; design; model design; models and simulation; mutant; novel; pediatric department; pediatric pharmacology; pharmacokinetic model; prevent; programs; research and development; response; simulation; sound

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.

描述（由申请人提供）：设计和执行儿科临床药物试验的长期职业目标，重点是了解感染性疾病治疗的药理学，我通过这个指导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。随着我在2007年6月完成儿科传染病奖学金，这个职业发展计划将为我提供必要的组成部分，在儿科传染病和药理学之间的接口独立的医生科学家的职业道路通过以下：（1）儿科药理学和临床试验设计的正规教育，包括药理学高级课程，药理学研讨会和期刊俱乐部，在负责任的研究行为的培训，并在临床研究在加州大学圣地亚哥分校（UCSD）硕士学位，（2）在UCSD的儿科药理学研究单位（PPRU）和UCSD的国际孕产妇儿童青少年艾滋病临床试验（IMPAACT）组实验室的人口药理学建模，模拟和临床药理学分析技术的研究培训，以及（3）出版物、演示文稿和指导监督的结构化计划。这个建议是可行的，因为健全的职业发展和研究计划，以及从我的导师，咨询委员会和儿科系在加州大学圣地亚哥分校的大力支持。尽管全世界都在HIV感染儿童中使用抗逆转录病毒药物，但几乎没有药理学数据来确定目前的给药方案是否是最佳的。在UCSD PPRU主任Capparelli博士和UCSD母婴青少年HIV项目主任Spector博士的指导下，我将把研究重点放在影响拉米夫定、齐多夫定药代动力学和药效学的药理学决定因素以及HIV感染儿童的诊断上。通过模拟本提案中开发的群体模型的影响，我们将确定当前给药方案是否提供最佳血药浓度。这些数据对全世界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，并确保目前的指南为广泛年龄范围内的艾滋病毒感染儿童提供最佳剂量。