The Development of Drug Metabolising Enzymes and Their Influence on the Susceptibility to Adverse Drug Reactions in Children

Altered drug disposition in the developing child occurs as a result of both biochemical and physiological changes. The clearance of many drugs is dependent on their biotransformation in the liver and small bowel and consequently is developmentally determined by a number of factors including both the activity and abundance of enzymes involved in Phase 1 and 2 drug metabolism. Altered drug metabolism can lead to the development of adverse effects in neonates and small infants that are not generally seen in the adult population. For instance, the altered metabolism of sodium valproate in children under 3 years of age is thought to be responsible for a higher incidence of hepatotoxicity, the impaired metabolism of chloramphenicol in neonates has resulted in the grey baby syndrome (cyanosis and respiratory failure) and metabolic acidosis following the use of propofol in the critically ill child may be due to altered drug metabolism. This paper reviews the potential contribution of the ontogeny of a number of drug metabolising enzymes including cytochrome P450 and glucuronoslytransferases to the development of adverse drug reactions in children.