Effect of extracellular water volume on the distribution kinetics of .BETA.-lactam antibiotics as a function of age.

Publisher Website
Google Scholar
Abstract
The distribution kinetics of cefazolin in rats was examined at 4 different ages (1, 7, 50 and 100 wk). This steady state distribution volume of cefazolin, estimated from the plasma time course after i.v. injection of 20 mg/kg, varied between 136 ml/kg (50-wk-old rats) and 297 ml/kg (1-wk-old rats). The extracellular fluid volume, obtained from the steady state distribution volume of inulin, varied between 126 ml/kg (50-wk-old rats) and 370 ml/kg (1-wk-old rats). There was a good correlation between the steady state distribution volume of cefazolin and extracellular fluid volume (r = 0.977). The influence of changes on the value of the plasma unbound fraction and extracellular fluid volume on the tissue-to-plasma partition coefficient of .beta.-lactam antibiotics was simulated by using a physiological pharmacokinetic model. The results of the simulation showed that extracellular fluid volume is an important factor affecting the distribution volume of .beta.-lactam antibiotics and that plasma binding plays a minor role on it. The experimental and simulation results suggests that the change in the interstitial fluid volume is a determinant factor in the age-related changes in the distribution volume of .beta.-lactam antibiotics.

This publication has 4 references indexed in Scilit: