间歇性高容量血液滤过对肾替代治疗病人血清莫西沙星药物浓度的影响

Effects of pulse high-volume hemofiltration on serum concentration of moxifloxacin in patients with continuous renal replacement therapy

目的:研究间歇性高容量血液滤过(PHVHF)治疗时莫西沙星的血清药物浓度变化,为临床用药提供依据。方法:8名行PHVHF治疗患者在治疗开始60 min内匀速静滴莫西沙星400 mg,给药后不同时间收集滤器前、后血样和置换液,采用高效液相色谱法(HPLC)测定血清及置换液中莫西沙星浓度。用DAS 2.1.1软件计算药代动力学参数。结果:PHVHF治疗前后血尿素氮(BUN)及肌酐(SCr)、血清钾(K+)水平显著下降(P<0.05),血清钠(Na+)氯(Cl-)维持稳定。HPLC分析方法测定血滤患者血清及置换液中莫西沙星浓度,线性关系良好,准确度及精密度高。静滴莫西沙星400 mg后在该患者体内的药代动力学符合开放型二室模型。主要药代参数:峰浓度(Cmax)=(4.843±1.854)mg/L,半衰期(T1/2)=(4.822±2.126)h,达峰时间(Tmax)=(1.31±0.59)h,总体分布容积(Vd)=(82.63±24.69)L,总体清除率(CLtot)=(14.36±8.43)L/h,AUC/MIC90在MIC90值分别为0.25 mg/L、0.12 mg/L、0.03 mg/L时均大于100,Cmax/MIC90在MIC90值分别为0.25 mg/L、0.12 mg/L、0.03 mg/L时均大于10。结论:PHVHF治疗可明显改善肾功能,稳定内环境,部分清除血清中莫西沙星,但PHVHF治疗后血清药物浓度仍可达到针对病原菌的有效治疗浓度。

AIM： To study the changes of the serum moxifloxacin concentration in the patients with continuous renal replacement therapy when applied for pulse high-volume hemofiltration（PHVHF）.METHODS： The patients applied for PHVHF were intravenously given moxifloxacin at the dose of 400 mg in 60 min.Blood samples were collected from the arterial（input） and venous（output） lines of the extracorporeal circuit immediately at different time points after the beginning of infusion,and replacement fluid was taken at the corresponding time points.The serum concentration of moxifloxacin was measured by high-performance liquid chromatography（HPLC）.The pharmacokinetics parameters were determined using DAS 2.1.1 software.RESULTS： Two-compartment model was used to achieve the best concentration-time relation of moxifloxacin.The levels of blood urea nitrogen（BUN）,serum creatinine（SCr） and serum K＋ were obviously decreased after application of PHVHF（P0.05）.The peak serum concentration（Cmax） of moxifloxacin was（4.843±1.854） mg/L.The half-life（T1/2） was（4.822±2.126） h and the peak time（Tmax） was（1.31±0.59） h.The total volume of distribution（Vd） was（82.63±24.69） L.The total clearance（CLtot） was（14.36±8.43） L/h.All the ratios of area under the concentration-time curve（AUC） to 90% minimal inhibitory concentration（MIC90） were more than 100 when the values of MIC90 were 0.25 mg/L,0.12 mg/L and 0.03 mg/L.All the values of Cmax/MIC90 were more than 10 when the values of MIC90 were 0.25 mg/L,0.12 mg/L and 0.03 mg/L.CONCLUSION： Application of PHVHF obviously improves the renal functions and eliminates a part of moxifloxacin in the serum.However,the serum concentration of moxifloxacin remains at the effective level for controlling the pathogenic bacteria.