The Children's Hospital Medical Center (CHMC) in Cincinnati has made commitments of infrastructure and key personnel consistent with the resolve to establish a Pediatric Pharmacology Research Unit (PPRU). The confluence of resources now engaged in pharmaceutical clinical trials including: 1) an NIH-funded Clinical Research Center (CRC), 2) a Clinical Trials Administration Program, 3) a Vaccine Testing and Treatment Unit,4) ongoing multicenter participation both originating at CHMC (e.g Pediatric Rheumatology Clinical Trial Coordination Center), or as part of a network (e.g. Children's Cancer Group, Neonatal Network, and the Maternal-Fetal Medicine Unit program) make commitment to a PPRU a logical next step. Advantages of a PPRU at CHMC would be the institution's expertise in clinical neuroscience, a familiarity with biopharmaceutics and gene therapies, a breadth of distinguished Clinical Investigators in all important areas of Pediatric Subspecialty, and access to substantial clinical material in every age-group and disease category. The CHMC PPRU will be located within the existing CRC inpatient and outpatient facilities and will complement and enrich existing CRC capability and utilization. The CHMC PPRU will be Directed by Dr. Sallee, a child psychiatrist/clinical pharmacologist, with extensive experience in all aspects of clinical trials and with existing linkages to the pharmaceutical industry and the FDA. Expertise in pediatric pharmacology at CHMC is evidenced by the volume and breath of both individual investigator initiated and pharmaceutical industry supported projects. Within our PPRU core faculty we have expertise in all aspects of the drug development process, including preclinical investigation of drug metabolism (metabolite identification and isozyme-specific metabolic pathways), initial testing of drugs in humans (Phases I, II), comprehensive evaluation of pharmacodynamic effects and surrogate markers, pharmacokinetic evaluations, and assessments of safety and efficacy (Phases II, III, & IV) and drug interactions (Phases III, IV). The CHMC PPRU will have the important capability of performing cytochrome P450 genotyping on study subjects. Advantages of a PPRU at CHMC are documented by our two network proposals; a Phase III safety, population PK/efficacy trial of recombinant human tumor necrosis factor receptor Fc fusion protein in JRA, and a rotavirus vaccine safety/efficacy trial; and two local protocols which evaluate calcium channel blocker (Amlodipine) to prevent cyclosporin/tacrolimus induced nephrotoxicity as well as a PK/PD study of a novel non-stimulant treatment (Tomoxetine) for ADHD.
