No abstract

The effect of protein binding upon the penetration of six-beta-lactam (three penicillins and three cephalosporins) antibiotics into tissue fluid was studied in humans. A cantharides blister technique was used. It was found that there was a linear relationship between the percentage of protein binding and the penetration into the blister fluid of the antibiotic as measured by the area under the curve of the protein-free fraction. This finding is further evidence that protein binding may have important influence upon the likely efficacy of an antimicrobial agent.

The pharmacokinetics of cefotaxime and moxalactam were compared in six healthy male volunteers after the administration of 1-g doses intravenously.Penetration of the compounds into tissue fluid was studied in cantharides-induced blisters. Both serum and tissue fluid levels of moxalactam were higher than those of cefotaxime. The elimination half-life of cefotaxime was 1.2 h, and that of moxalactam was 2.85 h. On the average, 50.5% of cefotaxime and 87.5% of moxalactam were recovered in the urine in 24 h. Urine was collected at 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 h after the injection of the antibiotic. Volumes passed were measured, and aliquots were stored at -20°C for assay the following day.The fluid formed in the superficial blisters resulting from the application of the cantharides plasters was sampled by a fine (23-gauge) needle 30 min after dosing and then hourly thereafter to 8 h (6 h in the case of cefotaxime). No bleeding occurred into the blister fluid. Fluid loss from the blister was prevented by use of a rapid-drying plastic spray dressing. The samples from the blisters were placed on preweighed, sterile, 6-mm disks which were then reweighed to ascertain the amount of fluid assayed.The assays were performed by a routine agar plate diffusion technique with pooled human serum standards for the assay of the serum samples; 75% serum standards were used for the blister fluids, this being the mean serum concentration of the blister fluid (6). The standards for the blister fluid were applied to identical disks in the same volume as that calculated, by weighing, to be on the test disk. The urine samples were assayed against standards prepared in phosphate-buffered saline (pH 6.5) in which the urine, if necessary, had been diluted.

No abstract