Antimicrobial pharmacokinetics and outcomes in vulnerable infants

脆弱婴儿的抗菌药物药代动力学和结果

• 批准号: 8270442
• 负责人: Matthew Laughon
• 金额: $ 13.31万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8270442
• 关键词: Adult; Adverse event; Antibiotics; Antifungal Agents; Antifungal Therapy; Applications Grants; Biological Assay; Birth Weight; Blood; Child; Childhood; Clinical Pharmacology; Clinical Research; Clinical Sciences; Clinical Trials; Clinical Trials Design; Collaborations; Communicable Diseases; Contracts; Critical Illness; Data; Development; Dose; Drug Kinetics; Environment; Epidemiology; Extramural Activities; Faculty; Fellowship; Fluconazole; Funding; Goals; Grant; Hour; Infant; Infant Health; Infection; Institutes; Intensive Care; Knowledge; Lead; Leadership; Learning; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Methods; Modeling; Mycoses; National Institute of Child Health and Human Development; National Institute of General Medical Sciences; Necrotizing Enterocolitis; Neonatal; Newborn Infant; North Carolina; Nurseries; Operative Surgical Procedures; Outcome; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Pharmacy Schools; Phase I Clinical Trials; Physicians; Physiology; Plasma; Population; Positioning Attribute; Premature Infant; Prophylactic treatment; Public Health; Publications; Qualifying; Recording of previous events; Research; Research Design; Research Infrastructure; Research Institute; Research Methodology; Research Training; Resources; Rifampin; Risk; Safety; Sampling; Scientist; Simulate; Site; Spottings; Staphylococcal Infections; Techniques; Technology; Therapeutic; Therapeutic Agents; Time; Training; Translational Research; United States National Institutes of Health; Universities; Utah; Validation; Vulnerable Populations; antimicrobial; antimicrobial drug; career; career development; congenital heart disorder; design; drug development; experience; high risk; high risk infant; improved; models and simulation; novel; novel strategies; older patient; open label; patient oriented research; pediatrician; pharmacodynamic model; planetary Atmosphere; prevent; programs; prophylactic; prospective; research and development; sample collection; skills; ward

DESCRIPTION (provided by applicant): The candidate is a neonatologist with strong training in epidemiology and a proven commitment to the study of patient-oriented research, with a desire to develop clinical pharmacology skills. The candidate's long-term career goal is to advance public health by improving drug safety and dosing in infants. The candidate's short- term career goals for the K23 program are to: 1) acquire knowledge and skills in clinical pharmacology; 2) develop the professional skills to successfully lead a PK/PD clinical trial research team; and 3) produce a critical mass of preliminary data and publications to support an R01 grant application and establish a program of independent research in clinical pharmacology. The proposed research plan, career development activities, mentorship team, and institutional environment are all uniquely suited to assist the applicant in achieving these goals. Although antibiotics are the most commonly used medications in hospitalized infants, dosing for infants is often extrapolated from data obtained in older children and adults. Fluconazole and rifampin are two antimicrobials commonly used in the nursery for which pharmacokinetic data can be improved. Dr. Laughon will use an integrative approach to investigate the pharmacokinetics and pharmacodynamics of these two agents in premature infants. This approach will include: application of sparse sampling methodologies; population PK/PD modeling; development of dried blood spot technology; a dual center PK trial; and a multi- site PK trial. This proposal will capitalize on unique opportunities provided by the Fluconazole Prophylaxis trial (PI: Benjamin, mentor), the NICHD PPRU open label fluconazole trial, and the Duke fluconazole trial. Dr. Laughon will also have access to the resources of the Duke Clinical Research Institute (Benjamin) and the Eshelman School of Pharmacy at UNC (Brouwer, co-mentor). To support the candidate's career development, he will participate in the UNC/Duke clinical pharmacology fellowship and become board certified in clinical pharmacology. The mentorship team assembled is uniquely qualified, and strengths include extensive clinical research experience; internationally recognized thought leadership in trial design, research methods, pharmacology, and PK/PD modeling; and a successful history of mentorship of junior faculty. Dr. Laughon's K23 proposal will provide him with the opportunity to learn PK/PD modeling and simulation techniques and to develop a dried blood spot assay in addition to refining clinical trial methodologies to maximize information gained from the limited samples available in this vulnerable population. The research environment including the Translational and Clinical Sciences Institute at UNC and the DCRI at Duke provide a productive, collegial, and collaborative atmosphere in which to pursue the above research and training goals. At the conclusion of this program, Dr. Laughon will be positioned to be an independent physician-scientist leading a research team.

描述（由申请人提供）：候选人是一名在流行病学方面受过良好培训的药理学家，并致力于以患者为导向的研究，希望发展临床药理学技能。候选人的长期职业目标是通过提高婴儿药物安全性和剂量来促进公共卫生。K23项目的候选人的短期职业目标是：1）获得临床药理学的知识和技能; 2）发展成功领导PK/PD临床试验研究团队的专业技能; 3）产生大量的初步数据和出版物，以支持R 01资助申请，并建立临床药理学独立研究项目。拟议的研究计划，职业发展活动，导师团队和机构环境都是唯一适合帮助申请人实现这些目标。虽然抗生素是住院婴儿最常用的药物，但婴儿的剂量通常是根据年龄较大的儿童和成人的数据推断的。氟康唑和利福平是托儿所常用的两种抗菌药物，其药代动力学数据可以改进。Laughon博士将采用综合方法研究这两种药物在早产儿中的药代动力学和药效学。这一办法将包括：稀疏采样方法学的应用;群体PK/PD建模;干血斑技术的开发;双中心PK试验;和多中心PK试验。本提案将利用氟康唑预防试验（PI：Benjamin，mentor）、NICHD PPRU开放标签氟康唑试验和杜克氟康唑试验提供的独特机会。Laughon博士还将获得杜克临床研究所（本杰明）和Eshelman药学院（布劳威尔，共同导师）的资源。为了支持候选人的职业发展，他将参加剑桥/杜克临床药理学奖学金，并获得临床药理学委员会认证。组建的导师团队具有独特的资格，优势包括丰富的临床研究经验;在试验设计，研究方法，药理学和PK/PD建模方面的国际公认的思想领导力;以及初级教师的成功导师历史。Laughon博士的K23提案将为他提供学习PK/PD建模和模拟技术的机会，并开发一种干血斑试验，此外还将改进临床试验方法，以最大限度地从这一脆弱人群的有限样本中获得信息。研究环境，包括转化和临床科学研究所在斯坦福大学和DCRI在杜克提供了一个富有成效的，合议和协作的氛围，在追求上述研究和培训目标。在该计划结束时，Laughon博士将被定位为一名独立的医生科学家，领导一个研究团队。