Characteristics of ceftriaxone binding to immunoglobulin G and potential clinical significance

Abstract

The interaction between immunoglobulin G (IgG) and ceftriaxone was studied. Using an ultrafiltration method, we performed dose ranging studies at a ceftriaxone concentration range of 1 to 720 micrograms/ml in the presence of various concentrations of human IgG, human serum albumin (HSA), and combinations of IgG and HSA at pH 7.4 and 37 degrees C. The results showed that ceftriaxone binding to IgG was nonlinear and was consistent with the presence of two binding sites that possess different binding capacities and affinities. Except for increased peak percent binding as the IgG concentration increased, the binding characteristics did not change with IgG concentration. Binding to HSA was consistent, with the presence of only one high-affinity binding site. A mathematical model based on the observed data was constructed; this model was used to predict protein binding at various concentrations of drug, IgG, HSA, or combinations of IgG and HSA in buffer and in plasma medium. Correlations between the observed versus the predicted values were excellent in both media. Simulations with the model indicated that patients with hypergammaglobulinemia have an increased potential of being exposed to prolonged subinhibitory concentrations of ceftriaxone if the drug is given once every 24 h.