Effect of the Ratio of Surface Area to Volume on the Penetration of Antibiotics into Extravascular Spaces in an in Vitro Model

The penetration of cephapirin into extravascular spaces of various volumes and ratios of surface area to volume (SA/V) was studied in an in vitro kinetic model. The SA/V ratio was found to be an important determinant of the kinetics of these spaces. The greater the surface area in relation to the volume of the extravascular space, the more closely its kinetics mimicked those of the intravascular space - that is, the higher the absolute peak concentration of drug achieved in the extravascular space, the greater the peak-to-trough fluctuation and the more quickly the peak concentration of drug was reached. Extravascular spaces with similar SA/V ratios demonstrated similar kinetics. Data from various models of extravascular fluid in humans and animals were reviewed, and the kinetics of these extravascular spaces were also found to be determined, at least in part, by the SA/V ratios of the spaces.