Optimizing Pediatric Dosing: A Developmental Pharmacologic Approach

Gail D. Anderson, Ph.D.; Anne M. Lynn, M.D.


Pharmacotherapy. 2009;29(6):680-690. 

In This Article


After absorption, a drug is distributed to various body compartments according to its physiochemical properties, such as its molecular size, ionization constant, and relative aqueous and lipid solubilities. In neonates and infants, an increased total body water:body fat ratio contributes to an increase in the volume of distribution for hydrophilic drugs such as gentamicin,[17] linezolid,[18] phenobarbital,[10] and propofol.[16] As a result, these patients require enlarged loading doses (in milligrams/kilogram) to achieve therapeutic concentrations. Given the increased volume of distribution of propofol, a large initial infusion and an initial loading dose are needed to achieve plasma concentrations similar to those measured in adults.[19] The volume of distribution of more highly lipophilic drugs (e.g., diazepam, lorazepam) are similar in infants and adults.[20]


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