Nadstawek J, Weil H P, Frenkel C, Kühnen E, Mauersberger W, Hörnchen U
Institut für Anästhesiologie, Universität Bonn.
Immun Infekt. 1989 Dec;17(6):212-6.
Ceftazidime serum concentrations and cerebrospinal fluid (CSF) penetration across non-inflamed meninges were evaluated in 10 patients after intravenous application of 2 g ceftazidime over a period of 30 min. After a continuous increase during infusion the highest level of ceftazidime in serum with 172.27 micrograms/ml (+/- 60.43 micrograms/ml) was ascertained at the end of the infusion. The further development demonstrated a continuous decrease of serum concentrations. Concentrations in serum followed a two-compartment open kinetic model. Mean distribution volume was 17.6 l, the total clearance was 142.97 ml/min, half-life was 1.8 h and the determined area under the curve was 139.89 micrograms x min/ml. Penetration of ceftazidime into CSF could only be pointed out in 5 patients. The highest level with 5.11 micrograms/ml (+/- 1.2 micrograms/ml) was observed 32 min after starting the infusion. A steady state with CSF-concentrations over 2 micrograms/ml could be ascertained during the following 4 hours in these patients. Obviously high statistic significance (p less than or equal to 0.01) was present when penetration into CSF was correlated to body surface area (BSA) using the exact Fisher test with Yates correction. Penetration of ceftazidime into CSF across non-inflamed meninges with therapeutic concentrations over a period of 4 hours could only be achieved when BSA was less than 1.95 m2. Further investigations in more patients are necessary to evaluate if BSA is the only parameter which affects distribution of ceftazidime into CSF.
在10例患者静脉输注2g头孢他啶30分钟后,评估了头孢他啶的血清浓度及穿过非炎性脑膜的脑脊液(CSF)渗透率。输注期间血清中头孢他啶水平持续上升,输注结束时测得血清中头孢他啶最高水平为172.27微克/毫升(±60.43微克/毫升)。随后血清浓度持续下降。血清浓度符合二室开放动力学模型。平均分布容积为17.6升,总清除率为142.97毫升/分钟,半衰期为1.8小时,曲线下面积为139.89微克·分钟/毫升。仅在5例患者中发现头孢他啶可穿透进入脑脊液。输注开始32分钟后观察到最高水平为5.11微克/毫升(±1.2微克/毫升)。在随后4小时内,这些患者脑脊液浓度可维持在2微克/毫升以上的稳态。当采用精确的Fisher检验并进行Yates校正,将脑脊液渗透率与体表面积(BSA)相关联时,具有明显的高度统计学意义(p≤0.01)。只有当体表面积小于1.95平方米时,头孢他啶才能在4小时内以治疗浓度穿过非炎性脑膜进入脑脊液。需要对更多患者进行进一步研究,以评估体表面积是否是影响头孢他啶向脑脊液分布的唯一参数。