We are submitting a proposal for 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 only 19 pediatricians world-wide who has this dual certification and is the only Neonatologist among them. Dr. van den Anker moved to Children's National Medical Center (CNMC) in 2002 to become Director of Pediatric Clinical Pharmacology, and Professor of Pediatrics and Pharmacology at the George Washington University School of Medicine and Health Sciences (GW). Significant institutional and departmental commitments, including financial support as documented in this application have been provided to build a premier academic pediatric clinical pharmacology research program. Dr. van den Anker is currently the P.I. of a number of external grants in support of his pharmacological research. His expertise is in the area of developmental changes in pharmacokinetics and pharmacodynamics of frequently used medicines in neonates. Dr. van den Anker has published over 100 peer-reviewed articles in the field of developmental and neonatal pharmacology, primarily focusing on the effect of renal function on clinical pharmacokinetics of frequently used medicines in the newborn. Until now Dr. van den Anker has been using traditional pharmacokinetic study design and analysis in his research. Despite his research productivity, there are recent advances in the methodology for studying pharmacokinetics, pharmacodynamics and pharmacogenetics that he needs to learn. The K24 award would offer him the opportunity for gaining skills in the new fields of population pharmacokinetics and pharmacogenomics and to mentor junior faculty in pediatric pharmacology research. In this proposal, he plan to mentor 4 junior pediatric faculty members who are conducting pharmacological studies in the areas of hematology, infectious diseases, anesthesiology and psychiatry. In addition, he will perform a research project that will focus on the development of a pharmacokinetic/pharmacodynamic (PK/PD) model for morphine dosing in preterm infants that will incorporate developmental changes (UGT2B7 activity and renal function) and pharmacogenetic information (UGT2B7 gene, COMT- and the (-opioid receptor gene) relevant to morphine pharmacokinetics and pharmacodynamics. The long-term goal of the proposed investigation is to improve the use of morphine in critically ill premature neonates. [unreadable] [unreadable]