Protein binding of ceftriaxone in extravascular fluids

Ceftriaxone binding in extravascular fluids and diluted plasma was characterized by equilibrium dialysis techniques and the data was subjected to Scatchard analysis. The extent of ceftriaxone binding in extravascular fluids (synovial, lymph, ascites, and pleural exudate) was less than plasma due primarily to lower albumin concentrations. Ceftriaxone capacity constants were highly correlated (r2 = 0.900, p less than 0.001) with measured albumin concentrations (range of 43 g/L for albumin to 4.7 g/L for one of the pleural exudate samples). The binding affinity constant (M-1 x 10(-4] was comparable for plasma (3.67), synovial fluid (4.14), and lymph (3.40), but was lower for ascites (2.37) and pleural fluid (range of 2.77 to 0.31). Plasma samples diluted with plasma water (range of 100 to 3%) exhibited a common affinity constant (mean value 4.03 x 10(4) M-1) and capacity constants which correlated directly with albumin concentration (r2 = 0.998, p less than 0.001). Analysis of these observations suggests that extravascular binding of ceftriaxone can readily be predicted if extravascular albumin concentration and corresponding disease-state plasma protein binding are known.