肾功能亢进患者万古霉素的药代动力学及谷浓度影响因素研究

The influencing factors of pharmacokinetics of Vancomycin and its trough concentration in patients with augmented renal clearance

目的研究万古霉素在肾功能亢进（Augmented Renal Clearance，ARC）患者体内的血药谷浓度和药代动力学特点，并对其血药谷浓度影响因素进行分析。方法回顾性分析2013年7月至2017年7月苏州市立医院本部收治并使用万古霉素进行治疗同时有稳态谷浓度测定数据的成人患者资料，根据估算肾小球滤过率（eGFR）分为ARC组[eGFR〉130ml／（min·1．73m^2）]和肾功能正常组[eGFR=50～130ml／（min·1．73m^2）]。利用贝叶斯反馈法计算其万古霉素药代动力学参数，采用Logistic单因素和多因素回归分析筛选血药谷浓度的影响因素。结果共收集291例患者共计291次万古霉素血药谷浓度数据，分为ARC组78例和肾功能正常组213例。ARC组万古霉素日均剂量较肾功能正常组大f（2150±550）mg比（1812±453）mg，P=0．000]，但是平均谷浓度低于肾功能正常组[（8．3±6．4）ms／L比（13．6±7．2）mg／L，P=0．0001，仅有16．7％的ARC患者血药谷浓度在目标血药谷浓度（10—20mg／L）范围，与肾功能正常组相比差异有统计学意义（16．7％比46．5％，P=0．000）。ARC患者万古霉素的表观分布容积较肾功能正常组显著增大[（69．3±27．7）L比（60．5±21．3）L，P=0．000]，清除率明显高于。肾功能正常组f（7．0±0．9）L／h比（4．3±0．4）L／h，P=0．000]。回归分析显示患者年龄、体重、用药前肌酐是万古霉素血药低谷浓度的独立相关因素。结论ARC患者万古霉素血药谷浓度达标率低，药代动力学参数与肾功能正常者相比也具有较大差异，患者的年龄、体重和用药前肌酐水平对血药谷浓度影响较大。

Objective To observe the characteristics of pharmacokinetics of Vancomycin and its serum trough concentration in patients with augmented renal clearance （ARC）, and to analyze the influencing factors of trough concentration of Vancomycin. Methods A retrospective analysis was conducted in steady- state trough concentrations of Vancomycin in adult patients of Suzhou Municipal Hospital from July 2013 to July 2017. According to the estimated glomerular filtration rate （eGFR）, the patients were divided into the ARC group [eGFR 〉130 ml/（min·1.73 m^2）] and the normal renal function group [eGFR = 50-130 ml/（min·1.73 m^2）]. The pharmacokinetic parameters of Vancomycin were calculated by Bayesian feedback method. The influencing factors of Vancomycin were analyzed by univariate and multivariate factors Logistic regression analysis. Results There were 291 patients who were collected trough concentrations of Vancomycin including 78 patients in the ARC group and 213 patients in the normal renal fimction group. In the ARC group, the average daily dose of Vancomycin was much higher than that in the normal renal function group [（2 150±550）mg vs. （1 812±453）mg, P = 0.000], but the average trough concentration was much lower than that in the normal renal function group [（8.3±6.4）mg/L vs. （13.6±7.2）mg/L, P = 0.000]. Only 16.7% of the ARC patients had the trough concentrations of Vancornycin in the target range （10-20 mg/L）. Comparing with the normal renal function group, the difference was significant （16.7% vs. 46.5%, P = 0.000）. According to the pharmacokinetic parameters by Bayesian feedback method, the apparent volume of distribution （Vd） was significantly increased in the ARC group than the normal renal function group [（69.3±27.7）L vs. （60.5±21.3）L, P = 0.000], and clearance rate （CL） was significantly increased in the ARC group [（7.0±0.9） L/h vs. （4.3±0.4） L/h, P = 0.000]. Logistic regression analysis showed that the age, body weight, and the serum creatinine before administration were the independent factors of low trough concentration of Vancomycin. Conclusions The serum trough concentration of Vancomycin is significantly reduced in the ARC patients. The pharmacokinetic parameters in the ARC patients are significantly different from those with normal renal function. The age, body weight, and the serum creatinine before administration have more influences on the trough concentration of Vancomycin.