Cefixime penetration in human renal parenchyma

The diffusion of cefixime, a new orally active expanded-spectrum cephalosporin, was studied in 12 patients undergoing nephrectomy after receiving 200-mg oral doses every 12 h for 2 days. The patients were divided into two groups according to the time of perioperative sampling after the last dose: 4 h (group 1) and 12 h (group 2). Preoperative blood samples were taken just before administration of the last dose of cefixime. Simultaneous blood and tissue samples were collected perioperatively at 4 h (time to peak level) and 12 h (residual level). The intrarenal concentrations of cefixime were measured by an isocratic reversed-phase high-pressure liquid chromatographic (HPLC) assay. Concentrations in serum were determined by both microbiological and HPLC assays. The mean peak levels in serum were 3.41 +/- 0.43 micrograms/ml (group 1), and the residual levels averaged 1.54 +/- 1.17 micrograms/ml (group 2). The diffusion in renal parenchyma was not significantly different in the cortexes and medullas of both groups of patients: 5.7 to 6.4 micrograms/g in group 1 and 4.6 to 4.7 micrograms/g in group 2. The decrease in cefixime concentrations was slower in tissue than in serum; the ratios of concentrations in tissue to those in serum were 3.5 to 3.6 and 1.7 to 1.9 at 4 and 12 h, respectively. The intrarenal concentrations of cefixime remained higher than the MIC for the most susceptible gram-negative bacteria during the time interval between the administration of two doses.