Leroy A, Oser B, Grise P, Humbert G
Department of Biochemistry, University of Rouen, Hôpital Charles Nicolle, France.
Antimicrob Agents Chemother. 1995 Jun;39(6):1240-2. doi: 10.1128/AAC.39.6.1240.
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.
对一种新型口服活性广谱头孢菌素头孢克肟的扩散情况进行了研究,研究对象为12例接受肾切除术的患者,他们每12小时口服200毫克剂量,持续2天。根据最后一剂药后围手术期采样时间,将患者分为两组:4小时组(第1组)和12小时组(第2组)。术前血样在最后一剂头孢克肟给药前采集。围手术期在4小时(达到峰值水平的时间)和12小时(残留水平)同时采集血样和组织样本。头孢克肟的肾内浓度通过等度反相高压液相色谱(HPLC)测定法进行测量。血清浓度通过微生物学和HPLC测定法确定。血清中的平均峰值水平为3.41±0.43微克/毫升(第1组),残留水平平均为1.54±1.17微克/毫升(第2组)。两组患者皮质和髓质肾实质中的扩散情况无显著差异:第1组为5.7至6.4微克/克,第2组为4.6至4.7微克/克。头孢克肟在组织中的浓度下降比在血清中慢;组织与血清中浓度的比值在4小时和12小时分别为3.5至3.6和1.7至1.9。在两剂给药的时间间隔内,头孢克肟的肾内浓度始终高于最敏感革兰氏阴性菌的最低抑菌浓度(MIC)。