Pharmacokinetics in Pediatric Patients: Drug Metabolism

Pediatric hepatic drug metabolism and metabolizing enzymes differ significantly from those in adults.

In neonates, Phase I enzyme activities operate at a fraction of adult levels, ranging from 20– 40%.

By 6 months to 1 year of age, hepatic enzyme activity in infants begins to approach adult levels but becomes fully functional only by age 2.

This age-dependent development of Phase I enzymes significantly affects drug pharmacokinetics, impacting drug metabolism.

Notably, children 3–10 years old exhibit higher hepatic metabolism than adults. For instance, the metabolism of carbamazepine is notably increased in children, often necessitating higher doses in this subgroup.

Similar to Phase I enzymes, Phase II enzymes also show significant age-dependent variation, with glucuronosyltransferase activity being low in neonates and young children but approaching adult levels by adolescence.

In neonates, variations in enzyme activity can cause high levels of unconjugated bilirubin in the blood. It can also cross immature brain barriers, which may lead to kernicterus.