Volume of Distribution

In pediatric patients, apparent volume of distribution (Vd) is normalized based on body weight and expressed as L/kg. Extracellular fluid and total body water per kilogram of body weight are increased in neonates and infants, resulting in higher Vd for water-soluble drugs such as aminoglycosides and decreases with age. Therefore, neonates and infants often require higher individualized doses by weight (mg/kg) than older children and adolescents to achieve the same therapeutic serum concentrations.14-17 Neonates and infants have a lower normal range for serum albumin (2-4 g/dL, 20-40 g/L), reaching adult levels after 1 year of age. This affects highly protein-bound drugs such as phenytoin, resulting in lower total serum concentrations needed to achieve therapeutic, unbound serum concentrations.14

As premature neonates have lower body adipose composition compared to older children and adults, they have a decreased Vd for lipid-soluble drugs such as midazolam and require lower doses by body weight. Lipid-soluble drugs may also reach higher concentrations in the CNS due to an immature blood-brain barrier.18

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