持续和间断两种静脉注射方法时万古霉素在脑脊液中的药代动力学特征比较

Comparison of pharmacokinetics characteristics of vancomycin in cerebrospinal fluid after administration by continuous and interim intravenous infusion

目的：比较神经外科手术患者术后持续静脉注射和间断静脉注射应用万古霉素时脑脊液中的药代动力学特征。方法选择首都医科大学附属北京天坛医院20例神经外科术后进入重症加强治疗病房（ICU）且接受万古霉素预防颅内感染治疗的患者，用简单随机化方法将患者分为持续静脉注射和间断静脉注射万古霉素两组，每组10例。持续静脉注射组患者开始静脉泵入15 mg/kg负荷剂量万古霉素1～2 h，随后以30 mg/kg的剂量匀速泵入24 h；间断注射组患者以15 mg/kg万古霉素泵入1～2 h，然后每12 h 1次。采用二维液相色谱法测定两组患者不同时间点的脑脊液中万古霉素的浓度，计算其药代动力学参数，并观察其不良反应。结果持续静脉注射组药物浓度-时间曲线下面积（AUC）和最低抑菌浓度（MIC）的比值与间断静脉注射组比较差异无统计学意义（19.7±14.0比16.1±6.4，P＞0.05）。但持续静脉注射组脑脊液药物浓度12 h就能达到峰浓度（0.96±0.77）μg/mL，后达到了稳态浓度0.91～0.93μg/mL，并持续12 h；而间断静脉注射组脑脊液16 h 才达到峰浓度（0.92±0.47）μg/mL，随后2 h下降至（0.84±0.45）μg/mL，并仍然呈持续下降趋势。所有患者均未发现与用药相关的不良反应。结论持续静脉注射和间断注射万古霉素两种用药方法在神经外科术后无颅内感染患者中，脑脊液中能达到同样的药物效果，但持续静脉注射给药能较快达到峰浓度，而且随后的浓度波动较小。

Objective To compare the difference in pharmacokinetics characteristics of vancomycin in cerebrospinal fluid between administration by continuous infusion and interim infusion.Methods Twenty postoperative patients in the Department of Neurosurgery of Beijing Tiantan Hospital, Capital Medical University admitted into intensive care unit （ICU） to receive vancomycin for prophylaxis of intracranial infection were enrolled, and they were randomly distributed to a continuous intravenous infusion group and a interim intravenous infusion group, each group 10 cases. In continuous intravenous infusion group, the patients received a loading dose of vancomycin （15 mg/kg） by continuous intravenous pump infusion for 1 - 2 hours followed by 30 mg/kg vancomycin in a constant pump infusion rate for 24 hours; while in interim intravenous infusion group, the patients received 15 mg/kg vancomycin administered by intravenous pump infusion for 1 - 2 hours, once every 12 hours. The concentration of vancomycin in the cerebrospinal fluid at different time points was measured by two-dimensional liquid chromatography （2D-LC） method, the parameters of pharmacokinetics were calculated in the two groups, and the adverse reaction was observed.Results The comparison between the ratio of areas under the concentration-time curves （AUC） and minimum inhibitory concentration （MIC） of the continuous and interim groups showed no significant difference （19.7±14.0 vs. 16.1±6.4,P 〉 0.05）. However, in the continuous intravenous infusion group, the drug concentration reached the peak value （0.96± 0.77）μg/mL at 12 hours, and later revealed a plateau concentration 0.91-0.93μg/mL for 12 hours; while in the intravenous infusion interim group, the drug concentration reached the peak value （0.92±0.47）μg/mL at 16 hours, in the later 2 hours declined to （0.84±0.45）μg/mL, and afterwards still had a tendency of persistent declination. In all the patients, no any adverse reaction related to the drug occurred.Conclusion Continuous intravenous infusion and interim intravenous infusion of vancomycin for the postoperative neurosurgical patients without intracranial infection have the similar efficacy of medication, but the former can achieve the peak concentration faster and later the fluctuation of drug concentration in cerebrospinal fluid is smaller than those in the latter.