| 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 Drug Research Unit (PDRU) at the University of Tennessee
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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Christensen ML, Mottern RK, Jabbour JT, Fuseau EL: Pharmacokinetics of sumatrip-tan nasal spray in adolescents. J Clin Pharmacol 43:721-726, 2003. Christensen ML, Chesney RW. Has the 'Therapeutic Orphan' finally
been adopted? Editorial. J Pediatr Pharmacol Ther 2003; 8:175-176. Christensen ML, Meibohm B, Capparelli EV, Velasquez-Mieyer P, Burghen GA, Tamborlane WV. Single and multiple dose pharmacokinetics of pioglitazone in adolescents with type 2 diabetes. J Clin Pharmacol 2005; 45(10):1137-1144 Lustig RH, Mietus-Snyder ML, Bacchetti P, Lazar AA, Velasquez-Mieyer PA, Christensen ML. Insulin dynamics predict response to insulin suppression or sensitization pharmacotherapy in obese children. J Pediatr 2006; 148(1):23-29 Elbahlawan L, Binaei S, Christensen ML, Zhang Q, Quasney MW, Dahmer MK. Beta2-adrenergic receptor polymorphisms in African American children with status asthmaticus. Pediatr Critical Care Med 2006;7:15-18 Crill CM, Storm MC, Christensen ML, Hankins CT, Jenkins MB, Helms RA. Carnitine supplementation in premature neonates: effect on plasma and red blood cell total carnitine concentrations, nutrition parameters and morbidity. Clin Nutr 2006; 25(6):886-896 Crill CM, Christensen ML, Storm MC, Helms RA. Relative bioavailability of carnitine supplementation in premature neonates. JPEN J Parenter Enteral Nutr. 2006; 30(5):421-425. |