Serum protein binding and extravascular diffusion of methoxyimino cephalosporins. Time courses of free and total concentrations of cefotaxime and ceftriaxone in serum and pleural exudate.
A new approach to the study of the distribution pharmacokinetics of variably bound beta-lactams is to plot the concentration time course of their free (dialysable) and total (free and bound) forms. In the present study, the 6-h concentration time course was plotted of the total and free concentrations of cefotaxime and ceftriaxone in serum and pleural exudate in 12 patients per group, after iv dosing with 1 g of either cefotaxime or ceftriaxone. Samples were taken at 0.5, 1, 1.5, 2, 3, 4 and 6h after dosing. The results of a study of similar design, but conducted over 24 h in ten patients per group, following iv dosing with either cefotaxime 1 g 12-hourly or ceftriaxone 1 g daily are also reported. Samples were taken at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 14, 16 and 24 h after dosing. Areas under the curve of free cefotaxime in pleural fluid were greater than those of free ceftriaxone, in both the 6 h (+54.6%) and 24 h studies (+29.8% after 12 h and +71.0% after 24 h). The free cefotaxime/free ceftriaxone Cmax ratio was 1.75 in the 6 h study. Cefotaxime was superior to ceftriaxone in terms of the diffusion of the free (antibacterially active) fraction into a typical inflammatory exudate. Assessment of the effects of protein binding must be taken into account in antibiotic pharmacokinetic profiles.
Scaglione
F
F
Institute of Chemotherapy, University of Milan, Italy.
Raichi
M
M
Fraschini
F
F
D000328:Adult; D001798:Blood Proteins / Q000378:metabolism*; D002439:Cefotaxime / Q000097:blood / Q000493:pharmacokinetics*; D002443:Ceftriaxone / Q000097:blood / Q000493:pharmacokinetics*; D004058:Diffusion; D005122:Exudates and Transudates / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010994:Pleura / Q000378:metabolism*; D011485:Protein Binding
D001798:Blood Proteins; D002443:Ceftriaxone; D002439:Cefotaxime