[In vitro study of ceftriaxone binding to blood]

Binding of ceftriaxone, a new third generation cephalosporin, to blood was studied in vitro. Steady state dialysis with 14C-ceftriaxone was used. Percentages of ceftriaxone bound to plasma within the range of therapeutic concentrations (10 to 1,000 microM) varied widely (80 to 50%). Indicating that the binding process is saturable, investigations performed with various isolated plasma proteins in physiologic concentrations show that ceftriaxone binds mainly to albumin, and marginally or not at all to alpha-1-acid glycoprotein, gammaglobulins, transferrin, haptoglobin, and lipoproteins. Albumin has a single binding site (n = 0.7) with moderate affinity (Ka = 72,000 M-1) for ceftriaxone. The presence of this site explains why ceftriaxone binds to plasma according to a saturable process. Only a small proportion (5%) of ceftriaxone (75-450 microM) binds to red blood cells in whole blood with a 50% hematocrit. A strongly significant inhibition of ceftriaxone (520 microM) binding to plasma was found with high bilirubin levels (230 microM) (24% decrease; p less than 0.01). A small but significant decrease in ceftriaxone (380 microM) binding to plasma was found with high serum oleic acid (1014 microM) or uric acid (1,800 microM) concentrations (2% decrease; p less than 0.05).