Drug metabolism importantly determines drug concentrations. The efficacy and safety of many drugs prescribed for children are, therefore, dependent on intraindividual and interindividual variation in drug-metabolising enzyme activity. During growth and development, changes in drug-metabolising enzyme activity result in age-related differences in drug disposition, most pronounced in preterm infants and young infants. The shape of the developmental trajectory is unique to the drug-metabolising enzyme involved in the metabolism of individual drugs. Other factors impacting drug metabolism are underlying disease, drug–drug interactions and genetic variation. The interplay of age with these other factors may result in unexpected variation in drug metabolism in children of different ages. Extrapolation of adult data to guide drug dosing in children should be done with caution. The younger the child, the less reliable is the extrapolation. This review aims to identify the primary sources of variability of drug metabolism in children, the knowledge of which can ultimately guide the practitioner towards effective and safe drug therapy.
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