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

De Wildt, S.N.

Expert Opinion on Drug Metabolism and Toxicology 7(8): 935-948

2011


ISSN/ISBN: 1744-7607
PMID: 21548840
DOI: 10.1517/17425255.2011.577739
Accession: 055207119

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Abstract
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. 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. 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.