title: Profound changes in drug metabolism enzymes and possible effects on drug therapy in neonates and children.
abstract: BACKGROUND
  There are profound changes that take place in drug metabolism enzymes during fetal and postnatal development. These changes may significantly impact drug therapy in children.
  
  
  METHODS
  A combination of focused and comprehensive literature searches using PubMed and reference lists (from inception to 7 November 2009) is undertaken to identify reports on in vitro and in vivo development of drug metabolism enzymes as well disposition of selected drugs and their effect in children. The article provides an update on development of drug metabolism enzymes and their impact on drug substrate disposition and disease, which may aid to improve clinical practice and optimally design clinical trials in children.
  
  
  CONCLUSIONS
  Drug metabolism enzyme activity changes profoundly throughout the continuum of postnatal development and often results in different disposition pathways than in adults. Genetics and co-morbidity interact significantly with these developmental changes. Translation of existing knowledge into age-adjusted dosing guidelines and clinical trial design is highly needed for there to be an improvement in drug therapy in children.
authors.affiliation: Erasmus MC Sophia Children's Hospital, Pediatric Surgery & Intensive Care, GJ Rotterdam, The Netherlands. s.dewildt@erasmusmc.nl
authors.forename: Saskia N
authors.initials: SN
authors.lastname: de Wildt
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D047109:Fetal Development / Q000187:drug effects*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic; D007223:Infant; D007231:Infant, Newborn; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods; D010599:Pharmacokinetics; D010641:Phenotype
chemical_list: D003577:Cytochrome P-450 Enzyme System; D000426:Alcohol Dehydrogenase; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)