title: Pediatric pharmacogenomics: a systematic assessment of ontogeny and genetic variation to guide the design of statin studies in children.
abstract: The dose-exposure-response relationship for drugs may differ in pediatric patients compared with adults. Many clinical studies have established drug dose-exposure relationships across the pediatric age spectrum; however, genetic variation was seldom included. This article applies a systematic approach to determine the relative contribution of development and genetic variation on drug disposition and response using HMG-CoA reductase inhibitors as a model. Application of the approach drives the collection of information relevant to understanding the potential contribution of ontogeny and genetic variation to statin dose-exposure-response in children, and identifies important knowledge deficits to be addressed through the design of future studies.
authors.affiliation: Section of Cardiology, Children's Mercy Hospital and Clinics, University of Missouri-Kansas City School of Medicine, 2401 Gillham Road, Kansas City, MO 64108, USA. jbwagner@cmh.edu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wagner
authors.forename: J Steven
authors.initials: JS
authors.lastname: Leeder
mesh_terms: D000328:Adult; D002648:Child; D008078:Cholesterol, LDL / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000188:drug therapy* / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010372:Pediatrics; D010597:Pharmacogenetics; D012107:Research Design
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors