万古霉素静脉持续输注时脑脊液药物代谢动力学变化

Study of concentration of vancomycin in serum and cerebrospinal fluid during continuous intravenous infusion

目的探讨静脉持续输注万古霉素后脑脊液药物代谢动力学的变化规律。方法选择开颅术后保留脑室引流的患者12例。于手术后12h内开始以万古霉素0.5g精确静脉内泵入60min,后以2g/24h匀速持续泵入,顺序采集静脉血和脑脊液标本,用高效液相色谱法测定万古霉素浓度。结果万古霉素首剂负荷量500mg泵入结束后1h脑脊液的药物浓度达到前期峰值为1.67±0.82mg/L,12h后即相对稳定(2.23±1.20mg/L～3.42±1.18mg/L)。万古霉素脑脊液稳态药物浓度达到并超过神经外科术后颅内感染常见致病菌葡萄球菌属的MIC90(2mg/L),其脑脊液穿透率,以脑脊液与血清药物浓度—时间曲线下面积之比计算为22%;脑脊液与血清最高药物浓度之比是13%。结论常规剂量万古霉素静脉持续输入时,脑脊液中稳态药物浓度可达到颅内感染主要致病菌(葡萄球菌)的MIC90水平,但为提高疗效,更高的剂量可能是需要的。

Objective Pharmacokinetics of vancomycin in serum and cerebrospinal fluid （CSF） were studied after continuous infusion.Methods Twelve neurosurgical postoperative patients with ventricular drainage were enrolled in this study.In each patient,a loading dose of vancomycin of 0.5g was administered for 1h followed by a continuous infusion of 2g/d.Venous blood and CSF specimens were collected vancomycin concentration in specimens and measured by high performance liquid chromatography.Results The earlier peak vancomycin concentrations in CSF were 1.67 ±0.82mg/L occurred at 1h after bolus dose （500mg vancomycin）.The respective steady state concentrations of vancomycin in CSF （2.23 ±1.20mg/L to 3.42 ±1.18mg/L）were achieved in 12h after administration,which exceeded the 90% minimum inhibitory concentration （2 mg /L） of common pathogens （Staphylococcus） in intracranial infection.Penetration rate of vancomycin in CSF,area under the CSF concentration curve （AUCCSF）/AUCserum was 22%,the rate of peak concentration （CSF/serum） was 13.Conclusions Steady state concentration of vancomycin in CSF can continue for long time by continuous infusion with conventional dose,which exceeded the 90% minimum inhibitory （MIC90） concentration of common pathogens （Staphylococcus） in intracranial infection.Higher dosage is possibly necessary in order to enhance effection.