In 1968 Dr. Harry Shirkey coined the term """"""""therapeutic orphans"""""""" to lament the paucity of information available to guide the safe and effective use of drugs in infants and children. Despite almost three decades of advances in drug therapy there has been little improvement in this situation. The proposal detailed herein is aimed at securing funding to support the research intrastructure of a center, which as part of a network of research centers, will be able to develop, initiate and conduct both single site and multi- institutional studies of drug therapy in infants and children. The purpose of such studies will be to provide an objective basis for the rational use of selected therapeutic agents in these patients and to provide the clinical data necessary for U.S. Food and Drug Administration approval for use in children. The Center for Drug Research (CDR) in the Department of Pediatrics at Case Western Reserve University under the direction of Jeffrey L. Blumer, Ph.D., M.D. has an almost ten year experience in developing and conducting clinical trials of drugs in infants and children. It is proposed that the CDR serve as the administrative and implementation framework for one of the units in the Network of Pediatric Pharmacology Research Units proposed by the National Institute of Child Health and Human Development. To this end several studies are proposed to meet the specific aims that will serve to anchor the Network. Specifically, two proposals are outlined for collaborative multi-center clinical trials related to pharmacokinetics and pharmacodynamics in children: 1) Randomized, Double-Blind Comparisons of the Pharmacokinetics and Pharmacodynamics of Dopamine and Dobutamine in Postoperative Cardiac Patients; 2) Propofol as a Sedative to Facilitate Mechanical Ventilation in Critically Ill Patients. Examples of the long history of the fruitful collaboration between the CDR and the pharmaceutical industry are detailed in: 1) Ciprofloxacin Pharmacology in Patients with Cystic Fibrosis (CF); and 2) Safety, Tolerance and Pharmacokinetic Evaluation of a Single Intravenous Dose of Meropenem in Hospitalized Infants and Children. In addition, two examples of CDR initiated proposals are described in: 1) Bumetanide Pharmacokinetics and Pharmacodynamics in Infants with Fluid Overload; and 2) A Comparison of the Efficacy and Safety of Ketamine-Midazolam-Atropine to Meperidine-Midazolam for Pediatric Oncologic Procedures. Finally, a description of the Center organization, environment, and professional training milieu is provided.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (SRC (06))
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Case Western Reserve University
Schools of Medicine
United States
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