Specifics of Metabolism in Children

The most significant developmental changes in pharmacokinetics relate to drug clearance, which is based primarily on the functionality of the hepatic and renal elimination pathways. Quantitatively, the most important hepatic elimination pathway of phase I metabolism is the cytochrome P450 (CYP) enzymatic family. The activity of its most important form, CYP3A4, is very low in foetus and newborns, but between 6 and 12 months of age it already reaches 50% of adult values. The catalytic activity of CYP2D6 in the foetal liver is about 1% of the activity in adults, in newborns up to one month it is about 30% and in children up to 5 years about 70%. In CYP2C9, the activity is about 50% by the age of 5 months, after which it is close to the activity of adults. Ontogenetic changes of phase II of metabolism are less known so far. In neonates, two-thirds of sulfotransferase is involved in conjugation reactions, whereas UDP-glucuronosyltransferase accounts for about one-third. With increasing age, their share in metabolism is reversed. Hepatic elimination of drugs may also be affected by transport proteins, such as P-glycoprotein, of which very little is known about ontogenesis. Extrahepatic metabolism is mainly represented by enzymes of the small intestine and lungs. However, almost no data is available on their developmental changes. The immaturity of enzymatic systems can cause specific side effects of drugs in children. For adequate and at the same time safe dosing of drugs, it is necessary to consider the ontogenetic changes of individual enzymatic systems depending on the age of the child.

Keywords: pharmacokinetics, children, drugs, metabolism.