Ontogeny of drug metabolizing enzymes in the neonate.
Fetal exposure to xenobiotics is modulated to a considerable degree by the metabolic capabilities of the mother and the placenta. However, once liberated from the uterine environment the neonate is instantly exposed to a wide array of new macromolecules in the form of byproducts of cellular metabolism, dietary constituents, environmental toxins and pharmacologic agents. The rapid and efficient biotransformation of these compounds by Phase I and Phase II drug-metabolizing enzymes is an essential process if the infant is to avoid the accumulation of reactive compounds that could produce cellular injury or tissue dysfunction. Genetic polymorphisms and environmental factors are known to contribute dramatically to individual variation in the activity of drug-metabolizing enzymes. More recently, it has become apparent that programmed, developmental, regulatory events occur - independent of genotype - which further add to individual variation in drug metabolism. An appreciation of the impact of ontogeny on the expression and functional activity of the major drug-metabolizing enzymes enables the practicing clinician to predict the ultimate consequence of drug administration in the neonate to help guide optimal drug therapy.
Blake
Michael J
MJ
Department of Pediatrics, University of Missouri - Kansas City, Division of Pediatric Pharmacology and Medical Toxicology, The Children's Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA.
Castro
Lisa
L
Leeder
J Steven
JS
Kearns
Gregory L
GL
D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004304:Dosage Forms; D004851:Epoxide Hydrolases / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D014166:Transferases / Q000378:metabolism
D004304:Dosage Forms; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D014166:Transferases; D004851:Epoxide Hydrolases