PMCID: PMC5847265 DOI: 10.1016/j.pcl.2012.07.008
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.
Pediatric clinics of North America
Adult; Child; Cholesterol, LDL; Dose-Response Relationship, Drug; Dyslipidemias; Genetic Variation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pediatrics; Pharmacogenetics; Research Design
Wagner, J. B., Leeder, J. Pediatric pharmacogenomics: a systematic assessment of ontogeny and genetic variation to guide the design of statin studies in children. Pediatric clinics of North America 59, 1017-1037 (2012).