Percentage of total body water and extracellular fluid volume both decrease as children grow and develop with time. Pediatric patients thus have a larger volume of distribution than adults, which directly affects the dosing of hydrophilic drugs such as beta-lactam antibiotics like ampicillin. Thus, these drugs are administered at greater weight-based doses or with adjusted dosing intervals in children to account for this key difference in body composition.
Infants and neonates also have less plasma proteins. Thus, highly protein-bound drugs have fewer opportunities for protein binding, leading to increased distribution. Drug metabolism primarily occurs via enzymes in the liver and can vary according to which specific enzymes are affected in a specific stage of development. Phase I and Phase II enzymes have different rates of maturation and development, depending on their specific mechanism of action (i.e. oxidation, hydrolysis, acetylation, methylation, etc.). Enzyme capacity, clearance, and half-life are all factors that contribute to metabolism differences between children and adults. Drug metabolism can even differ within the pediatric population, separating neonates and infants from young children.