| Publications :: | Pediatric
Pharmacology Research Center Many of the diseases that affect children have a genetic basis for their cause that offers therapeutic targets for drug development. Unfortunately, children have largely been excluded from the many therapeutic advances that have marked the last 50 years of medical research. The pediatric clinical pharmacology programs at The University of Tennessee, St. Jude Children’s Research Hospital, and Le Bonheur Children’s Medical Center strive to improve the understanding of the physiologic and molecular bases that underlie the relationship between drug disposition and drug effect and to translate this information into improved drug therapy regimens in children. Several prominent research programs have resulted from the collaboration among these institutions. The Pediatric Clinical Research Unit (PCRU) at the University of Tennessee Clinical and Translational Science Institute and Le Bonheur Children's Medical Center was created to further strengthen and expand the research directed toward improving drug therapy in children. Nearly all children will receive some form of medication therapy during childhood. Although medications continue to be used extensively in the pediatric population, our knowledge regarding their use remains limited. Childhood is a period during which there are significant maturational changes in the processes that govern drug disposition and effect. Age-dependent variation in drug disposition is larger than that due to genetic variation for most drugs. If one includes genetic polymorphisms, then differences in drug elimination in children can be as great as 40-fold or more. The implication is that children are placed at significant risk for therapeutic misadventures when prescribed a drug that has not been adequately tested. Several practical problems discourage the testing of drugs in children. First, the principal organs responsible for drug metabolism and elimination undergo significant developmental changes, necessitating the study of children in various age and size ranges. Secondly, genetics play an important role in childhood diseases such as cystic fibrosis, sickle cell anemia, asthma, obesity, and diabetes, as well as many other diseases. Understanding the genetic basis for diseases that have their origins in childhood would lead to therapeutic interventions that could prevent or delay disease onset. Genetic variation (like that which determines eye or hair color) also plays an important role in drug response. For example, variations in the target sites in the lungs for one of the most common drugs used in children with asthma, albuterol, may affect the response to this inhaled medicine. Thirdly, ethical concerns exist regarding the administration of unproven drugs to children. Fourth, the high cost and technical difficulties of implementing studies in children discourage completing the necessary studies. Finally, there exists a lack of trained investigators expert in the conduct of pediatric clinical pharmacology research. The pediatric clinical pharmacology research programs are a collaborative effort among investigators from the Department of Pediatrics in the College of Medicine, the Departments of Clinical Pharmacy and Pharmaceutical Sciences in the College of Pharmacy at the University of Tennessee and St. Jude Children’s Research Hospital. This long and productive relationship has resulted in support from the State of Tennessee in the Center for Pediatric Pharmacokinetics and Therapeutics, the National Institutes of Health (NIH) for Pediatric Pharmacology Research Unit, and the Children's Foundation Research Center for the research laboratories at Le Bonheur Children's Medical Center. The Children's Foundation Research Center has primarily supported the laboratory activities of the PPRU, which support ongoing clinical research studies to enhance the understanding of how children handle medications differently than adults. The PPRU laboratory activities also focus on bridging the knowledge generated by laboratory scientists to clinical application in the treatment of children with a variety of diseases. |
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Blumer J, Reed M, Steinberg F, O’Riodan MA, Rosen CL, Springer MA, Christensen ML, Glaze D, PPRU Network. Single dose pharmacokinetic evaluation of three different dose levels of zolpidem in children with sleep difficulties. Clin Pharmacol Ther 2008; 83:551-558. Howard-Thompson A, Christensen ML. Elevated trobramycin concentration following endotracheal administration in a preterm infant. J Pediatr Pharmacol Ther 2008; 13:88-92 Zhang Y, Mehrotra N, Budha NR, Christensen ML, Meibohm B. A tandem mass spectrometry assay for the simultaneous determination of acetaminophen, caffeine, phenytoin, ranitidine, and theophylline in small volume plasma specimens. Clinica Chimica Acta 2008; 398:105-112
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