Optimizing the Use of Methadone in Newborn Infants

描述（由申请人提供）：我们正在提交一份更新K24中期职业发展奖的提案，以支持John N. van den Anker， M.D, Ph.D. van den Anker博士的努力。van den Anker博士是委员会认证的儿科医生，也是临床药理学认证；他是世界上仅有的30位拥有双重认证的儿科医生之一，也是其中仅有的两位新生儿学家之一。van den Anker博士于2002年加入美国国家儿童医学中心（CNMC），担任儿科临床药理学主任，他目前是乔治华盛顿大学医学与健康科学学院（GWU）的儿科、药理学和生理学教授。重要的机构和部门的承诺，包括财政支持和捐赠主席（埃文和辛迪琼斯教授儿科临床药理学）自2005年以来提供了建立一个一流的学术儿科临床研究项目。van den Anker博士目前是一些外部NIH资助的私家侦探，以支持他的药理学研究。他的专长是发育和新生儿药理学领域，主要关注肾功能对新生儿常用药物的临床药代动力学的影响。他的第一个K24奖（2004-2009）为他提供了在人群药代动力学和药物基因组学的一般方面获得技能的机会，并指导3-4名初级教师进行儿科药理学研究。在此提案中，他计划继续指导3-4名在HIV/AIDS、精神病学和麻醉学领域进行药理学研究的初级教员。此外，他将执行一个研究项目，将重点放在美沙酮给药的药物动力学模型的发展，该模型将纳入与美沙酮药代动力学相关的发育变化（CYP2B6活性和肾功能）和药物遗传信息（CYP2B6基因）。拟议调查的长期目标是提高美沙酮在新生儿和幼儿中的安全有效使用。

DESCRIPTION (provided by applicant): We are submitting a proposal for a renewal of a K24 Mid-Career development Award to support the efforts of John N. van den Anker, M.D., Ph.D. Dr. van den Anker is a Board Certified Pediatrician who is also certified in Clinical Pharmacology; he is one of the only 30 pediatricians world-wide who has this dual certification and is one of the only two Neonatologists among them. Dr. van den Anker moved to Children's National Medical Center (CNMC) in 2002 to become Director of Pediatric Clinical Pharmacology, and he is currently Professor of Pediatrics, Pharmacology & Physiology at the George Washington University School of Medicine and Health Sciences (GWU). Significant institutional and departmental commitments, including financial support and an endowed Chair (Evan and Cindy Jones Professor of Pediatric Clinical Pharmacology) since 2005 have been provided to build a premier academic pediatric clinical research program. Dr. van den Anker is currently the P.I. of a number of external NIH grants in support of his pharmacological research. His expertise is in the area of developmental and neonatal pharmacology, primarily focusing on the effect of renal function on clinical pharmacokinetics of frequently used medicines in the neonate. His first K24 award (2004-2009) offered him the opportunity to gain skills in the general aspects of population pharmacokinetics and pharmacogenomics and to mentor 3-4 junior faculty members in pediatric pharmacology research. In this proposal, he plans to continue mentoring 3-4 junior faculty members who are conducting pharmacological studies in the areas of HIV/AIDS, psychiatry and anesthesiology. In addition, he will perform a research project that will focus on the development of a pharmacokinetic model for methadone dosing in neonates and young infants that will incorporate developmental changes (CYP2B6 activity and renal function) and pharmacogenetic information (CYP2B6 gene) relevant to methadone pharmacokinetics. The long-term goal of the proposed investigation is to improve the safe and effective use of methadone in neonates and young infants. PUBLIC HEALTH RELEVANCE: The area of opiate exposed pregnant/postpartum women, and in utero or postnatally opiate exposed neonates urgently needs research to identify more effective medication treatment strategies. The research proposed in this project will result in evidence-based dosing guidelines for use of methadone in opiate-exposed neonates and young infants.