EFFECT OF UREA ON THE IN-VITRO BINDING OF NETILMICIN TO RENAL TISSUE IN RATS

The binding and release kinetics of netilmicin to the rat renal cortex and medulla were studied at therapeutic concentrations, together with the effect of urea on the binding kinetics of netilmicin to this type of tissue. The study was carried out using an equilibrium dialysis te chnique, determining free netilmicin concentrations,lia a reverse phas e high-performance liquid chromatography technique with fluorescence d etection and precolumn derivatisation. The binding of netilmicin to th e renal cortex and medulla as a function of the free concentration pro ved to be linear, while the washout kinetics appropriately fitted a si gmoid function using the Weibull equation. Netilmicin binding to the r enal cortex and medulla was characterised by a high partition coeffici ent in both tissues, with no statistically significant differences bet ween the binding of the drug to either. Similarly, there were no stati stically significant differences in the washout kinetics of netilmicin from the renal cortex and medulla. Previous incubation of renal tissu e with urea significantly modified the washout kinetics of the compoun d from the renal cortex but not from the medulla, suggesting differenc es in the affinity of the drug for the renal cortex in situations of r enal impairment.