血液病患者万古霉素治疗血药浓度临床特点及影响因素分析

Therapeutic monitoring of vancomycin concentration and the interfering factors in patients with hematologic disease

目的分析血液病患者万古霉素治疗血药浓度的特点并探讨可能的影响因素。方法通过监测血液病患者(n=101)和非血液病患者(n=203)万古霉素的血药浓度,采用药动学软件JPKD计算万古霉素的清除率(CL)和表观分布容积(Vd),比较两组患者万古霉素血药浓度等药动学参数差异有无统计学意义,并分析伴发中性粒细胞缺乏和肾功能亢进(ARC)对血药浓度的影响。结果血液病组患者万古霉素血药浓度显著低于非血液病组[(9.89±5.12)mg/L比(11.79±5.70)mg/L,P=0.001],CL显著高于非血液病组[(6.07±2.16)L/h比(5.14±1.98)L/h,P<0.001],两组间V_d差异无统计学意义(P=0.061)。血液病患者伴发中性粒细胞缺乏或ARC可导致万古霉素血药浓度显著降低,其中伴发中性粒细胞缺乏者有68.42%血药浓度未达标(<10 mg/L),伴发ARC者有74.00%血药浓度未达标。结论伴发中性粒细胞缺乏或ARC可能是导致血液病患者万古霉素血药浓度偏低的主要原因,推荐实施治疗药物血药浓度监测以促进此类患者万古霉素的合理应用。

Objective To describe the clinical characteristics of serum concentration of vancomycin in patients with hematologic disease and find out the probable interfering factors that might affect the concentration.Methods All the patients(with hematologic disease,n=101;without hematologic disease,n=203)underwent therapeutic monitoring of vancomycin concentration.We used the pharmacokinetic software JPKD to estimate the clearance(CL)and the apparent distribution volume(Vd).Vancomycin concentration and the pharmacokinetic parameters of vancomycin were compared statistically between these two groups of patients.Analysis were also conducted to find out whether neutropenia or augmented renal clearance(ARC)would affect the concentration of vancomycin.Results The serum concentration of vancomycin was significantly lower in the patients with hematologic disease than in the patients without hematologic disease[(9.89±5.12)vs(11.79±5.70)mg/L],but the CL was significantly elevated[(6.07±2.16)vs(5.14±1.98)L/h].The V_d showed no significant difference between the two groups(P=0.061).Patients with neutropenia or ARC showed much lower serum concentration of vancomycin.Subtherapeutic trough concentration of vancomycin(<10 mg/L)were found in 68.42%of the neutropenic patients and 74.00%in the ARC patients.Conclusions Patients with hematologic disease have lower serum concentration of vancomycin,which may be due to neutropenia or ARC.Therapeutic drug monitoring is necessary for vancomycin therapy in the patients with hematologic disease.