Profound changes in drug metabolism enzymes and possible effects on drug therapy in neonates and children

Expert Opin Drug Metab Toxicol. 2011 Aug;7(8):935-48. doi: 10.1517/17425255.2011.577739. Epub 2011 May 8.

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alcohol Dehydrogenase / genetics
  • Alcohol Dehydrogenase / metabolism
  • Child
  • Child, Preschool
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Interactions
  • Fetal Development / drug effects*
  • Genetic Variation
  • Genotype
  • Humans
  • Inactivation, Metabolic*
  • Infant
  • Infant, Newborn
  • Oxygenases / genetics
  • Oxygenases / metabolism
  • Pharmacogenetics / methods
  • Pharmacokinetics*
  • Phenotype

Substances

  • Cytochrome P-450 Enzyme System
  • Alcohol Dehydrogenase
  • Oxygenases
  • dimethylaniline monooxygenase (N-oxide forming)