Effect of protein binding on simulated intravascular and extravascular kinetics of cefotaxime in an in vitro model.

The simulated intravascular and extravascular kinetics of cefotaxime were studied in an in vitro model to evaluate the effect of antibiotic protein binding in the "intravascular" and "extravascular" space. Intravascular fluid consisted of either phosphate-buffered saline, which has no cefotaxime binding, or 3% bovine albumin, which has 63% cefotaxime binding. Extravascular spaces were filled with phosphate-buffered saline, 1.5% bovine albumin (46.6% cefotaxime binding), or 3% bovine albumin. Cefotaxime (80 mg per dose) was infused every 3 h for eight doses, and intravascular and extravascular drug concentrations were measured after doses one and eight. The corresponding intravascular and extravascular spaces were at (phosphate-buffered saline) or approaching (3% bovine albumin) equilibrium by dose eight. There were marked differences in drug concentrations achieved in the various extravascular spaces, but all could be explained on the basis of differing amounts of albumin present and the resultant differences in cefotaxime binding.