Serum Protein Binding and Extravascular Diffusion of Cefodizime and Ceftriaxone

Abstract

The aim of the study was to investigate the concentration-time courses in serum and bronchial secretions of total and unbound cefodizime and ceftriaxone. These cephalosporins are similar in antibacterial spectrum, intrinsic activity and resistance to β-lactamases, and differ in serum protein binding and elimination half-life. 25 patients of either gender aged 48 to 68 years with acute exacerbation of chronic bronchitis were treated every day with 1g intramuscularly of cefodizime or ceftriaxone. Free and total concentrations of the tested antibiotics were determined in duplicate by HPLC, both in serum and bronchial secretion cleared from cells, at different times after the second dose. At 2, 4 and 6 hours, cefodizime was found to exhibit higher free concentrations in bronchial secretion than those observed for ceftriaxone, despite lower total blood and bronchial secretion concentrations. These data confirm that extravascular distribution of cephalosporins is influenced by the extent of serum protein binding. Moreover, serum protein binding seems to affect the unbound concentration of cephalosporins at the site of infection.