Prediction of the Distribution Volumes of Cefazolin and Tobramycin in Obese Children Based on Physiological Pharmacokinetic Concepts

Abstract

So as to estimate the appropriate dose of antibacterial drugs in obese children, prediction of the volume of distribution in these children was attempted based on physiological pharmacokinetic concepts which had been constructed from results in normal-weight children. Serum concentration–time data after intravenous drip infusions of tobramycin and cefazolin were analyzed using noncompartmental analysis of obese children in whom the degree of obesity ranged from 30 to 80%. Volume of distribution at steady state (V _ss) per total body weight of tobramycin was significantly less than that for normal-weight children (P < 0.05), whereas the value of cefazolin was almost equal to that for normal-weight children. The equation to express the difference of V_ss between cefazolin and tobramycin obtained in normal-weight children failed in obese children, suggesting that there is a large decrease in the extracellular space in obese children exceeding the interindividual variations in normal-weight children. The V _ss value (liter) for tobramycin was predicted by using the equation 0.261 · {ideal body weight (kg) + 0.4 · [total body weight (kg) – ideal body weight (kg)]}. The V _ss value of cefazolin was predicted to be 0.3 · (predicted V _ss of tobramycin) + 0.052 · total body weight (kg). A good correlation between the predicted and the observed V _ss values was obtained.