pediatrics
Pharmacokinetics in Children
Distribution
The Volume of distribution of drugs changes in children with aging. These age-related changes are due to changes in body composition (especially the extracellular and total body water spaces) and plasma protein binding. Higher doses (per kg of body weight) of water-soluble drugs are required in younger children because a higher percentage of their body weight is water (see figure Changes in body composition with growth and aging ). Conversely, lower doses are required to avoid toxicity as children grow older because of the decline in water as a percentage of body weight. Additionally, Adapted from Puig M: Body composition and growth. InNutrition in Pediatrics, ed. 2, edited by WA Walker and JB Watkins. Hamilton, Ontario, BC Decker, 1996. Many drugs bind to proteins, primarilyalbumin, alpha-1 acid glycoprotein, and lipoproteins; protein binding limits distribution of free drug throughout the body.Albuminand total protein concentrations are lower in neonates but approach adult levels by 10 to 12 months. Decreased protein binding in neonates is also due to qualitative differences in binding proteins and to competitive binding by molecules such as bilirubin and free fatty acids, which circulate in higher concentrations in neonates and infants. The net result may be increased free drug concentrations, greater drug availability at receptor sites, and both pharmacologic effects and higher frequency of adverse effects at lower drug concentrations. 