MODELING OF CEFTRIAXONE PROTEIN-BINDING USING EXTENDED LEAST-SQUARES

Using extended least squares implemented in the form of MK MODEL program, ceftriaxone binding data was modelled. In vitro and ex vivo binding experiments were performed by means of equilibrium dialysis and HPLC as the analytical method. Human serum albumin solutions as well as human plasma from healthy adults and healthy and normal neonates were used as the systems. It was observed that ceftriaxone binding decreased as a function of increasing drug concentration (in the range 10-500 mg L-1), decreased albumin concentration (from 45 g L-1 to 25 g L-1), and addition of bilirubin in pathologic concentrations (150 mg L-1) to the human serum albumin solutions. Decrease of the binding affinity was observed in the solutions containing bilirubin. Binding of ceftriaxone in plasma proteins in neonates was smaller than in adults, and it decreased further in icteric neonates. Data suggest that in this group, binding affinity and capacity are diminished, whereas in healthy neonates only affinity is lowered. Extended least squares modelling provides a rational way of weighing the experimental data and is a preferable tool for evaluation of binding parameters in the complex systems.