Influence of flow rate on the disposition of levofloxacin and netilmicin in the isolated rat lung

The objective of this study was to examine the influence of the rate at which the tissue is perfused on the disposition of levofloxacin and netilmicin in the pulmonary tissue, using an experimental model of the isolated rat lung. Analysis of the results was performed using two pharmacokinetic approaches. By stochastic analysis of outflow curves the corresponding statistical moments and derived distribution coefficient were calculated. Model-dependent analysis based on a three-compartment dispersion model was also applied to the outflow concentration data. A statistically significant decrease in the distribution coefficient was observed for both antibiotics when the flow rate was decreased. For levofloxacin this parameter takes values of 2.14 and 1.25 mL/g for 10 and 5 mL/min flow rates, respectively. In the case of netilmicin these values were 0.81and 0.39 mL/g for the higher and lower flow rates, respectively. Model parameters related to the distribution process were also modified as a consequence of the flow rate decrease. Tissue flow rate seems to be a determinant factor on the distribution of levofloxacin and netilmicin in the isolated rat lung.