Author/Editor     Primožič, S; Karba, R; Terzič, D; Kozjek, F
Title     Modeling of ceftriaxone protein binding using extended least squares
Type     članek
Source     Acta Pharm Jugosl
Vol. and No.     Letnik 41, št. 4
Publication year     1991
Volume     str. 369-78
Language     eng
Abstract     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 ceftriaxonc 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. Nitroxide free radicals were used as a model system to study the biotransformation of free radicals in rat liver tissue samples. The results indicate that in aerobic conditions iron ions can switch the commonly observed reduction of nitroxides into the prevalence of re-oxidation processes. These observations were confirmed by the experiments in aqueous solutions with homogeneous plexes. mixtures of reactants. The conclusions from this study confirm the general idea of oxygen toxicity and give an insight in the possible mechanisms sustaining radical vitality in vivo in the presence of iron ions or their com
Descriptors     CEFTRIAXONE
PROTEIN BINDING
SERUM ALBUMIN
BILIRUBIN
CHROMATOGRAPHY, HIGH PRESSURE LIQUID
BINDING SITES