肾衰患者连续性血液滤过时万古霉素的药效学及药动学研究

 目的 了解肾衰患者进行连续性静静脉血液滤过(continuous veno-venous hemofiltration，简称CVVH)过程中万古霉素的药效学及药动学特征，为万古霉素的合理使用提供依据。方法 采用荧光偏振免疫分析仪测定使用万古霉素第3天、第16天时，给药后不同时间血中药物浓度，以PKBP-N1药动学软件包对所测得的药物浓度-时间数据进行拟合，计算药动学参数。并监测用药过程中万古霉素血药浓度谷值及药效学指标。结果 进行CVVH时，万古霉素的体内药动学过程呈开放型二房室模型。其药动学参数为：使用万古霉素第3天时，t_1/2α=0.41 h，t_1/2β=5.75 h，Vc=21.92 L，c_max=22.81 μg·mL^-1，c^min=5.82 μg·mL^-1,CL=3.49 L·h^-1，V_SS=28.32 L。第16天时，t_1/2α=0.61 h，t_1/2β=33.23 h，V_c=12.92 L，c_max=38.70 μg·mL^-1，c_min=16.50 μg·mL^-1，CL＝0.376 L·h^-1,V_ss=17.69 L。维持万古霉素的血药浓度谷值在5～10 μg·mL^-1有效范围的情况下，其用药间隔由用药初期的q8 h逐渐延长为用药17 d后的q48 h。药效学指标提示，万古霉素从患者体内清除其敏感菌金葡球菌的时间为38 d。结论 进行CVVH治疗时，体内万古霉素的药动学过程是可变的。因此，必须加强对万古霉素血药浓度的监测，及时调整用药方案，以保证用药的安全和有效。

Investigation of the pharmacodynamics and pharmacokinetics of vancomyci n during continuous veno-venous hemofiltration therapy in a patient with renal failure

OBJECTIVE To investigate the pharmacodynamic and pharmacokinetic properties of vancomycin during continuous veno-venous hemofiltration (CVVH) therapy in a patient with renal failure.METHODS A patient with kidney failure received 0.5g vancomycin infusion during CVVH therapy.On 3^rd day and 16th day during the therapy,blood samples were collected after the dosing.The serum concentrations of vancomycin were measured by TDx.The pharmacokinetic parameters were calculated using PKBP-N1 software.The pharmacodynamic targets of vancomycin were observed.RESULTS The pharmacokinetics of vancomycin during CVVH was fitted well with open two-compartment model.On the 3^rd day of CVVH therapy, the pharmacokinetic parameters were:t_1/2α0.41 h,t_1/2β5.75 h,V_c 21.92 L,c_max 22.81 μg·mL^-1,c_min 5.82 μg·mL^-1,CL 3.49 L and V_ss 28.32 L,respectively.On the 16th day, the PK parameters were:t_1/2α 0.61 h,t_1/2β 33.23 h,V_c 12.92 L,c_max 38.70 μg·mL^-1,c_min 16.50 μg·mL^-1,CL 0.367 L and V_ss 17.69 L,respectively.The pharmacodynamic targets of vancomycin were body temperature,white blood count and bacteria in phlegm.CONCLUSION It demonstrated that the pharmacokinetic properties of vancomycin changed with time during CVVH treatment.Therefore,the monitoring of blood drug concentration during the therapy was necessary and the dosage regiment should be adjusted accordingly.