This program, entitled "Developmental and Translational Pharmacology of Pediatric Antimicrobial Therapy", is submitted as an application responsive to RFA-HD-10-026: Specialized Center in Research in Pediatric Developmental Pharmacology (RPDP) Program (U54). The overall theme of the proposed program at the UC San Diego is to bring together non-clinical and clinical experts in the fields of developmental physiology, pharmacology, and infectious diseases and conduct translational research to advance the field of pediatric developmental pharmacology. This program is comprised of 3 Main Projects;2 Pilot Projects and 4 Cores. The three main projects are "Colistimethate Dose Optimization in Infants and Children", "Drug-Drug Interactions between Pharmaceutical and Endogenous Antibiotics" and "Developmental Aspects of Aminopenicillin Renal Clearance". Each project utilizes the Administrative Core (A), the Pharmacometrics Core (B), the Quantitative Pharmacology Assay Core (C) and the Training and Outreach Core (D). Working together these projects and cores will characterize developmental changes in the disposition and potential toxicity of antimicrobial therapy. The program will capitalize on the discoveries made in basic science laboratories at UC Diego and extend these investigations in both non-clinical and clinical domains. The Cores will develop pharmacologic assays that are appropriate across the pediatric age continuum and utilize innovative modeling and simulation techniques to optimize the knowledge generated from these projects and help establish links between clinical and non-clinical findings. These projects and core activities will provide a rich training environment for future pediatric pharmacologist. While this RPDP program is focused to address developmental pharmacologic issues relating to antimicrobial therapy, understanding the determinants of Oat transporter maturation in both rat and humans has broad Implications for other classes of drugs undergoing renal excretion. PUBLIC HEALTH RELEVANCE: Effective antimicrobial therapy remains challenging in infants and young children due to immaturity in host defenses, increasing resistance to existing antibiotics and developmental changes in drug distribution, metabolism and elimination. This program will increase mechanistic understanding of developmental pharmacology and host Interactions with antimicrobial therapy.