摘要目的 探讨下呼吸道感染重症患者万古霉素群体药代动力学(PPK),为重症患者万古霉素的个体化治疗提供依据.方法 收集2011年11月至2012年11月在我院呼吸科普通病房和呼吸科ICU(RICU)住院的下呼吸道感染同时使用万古霉素治疗的重症患者.留取万古霉素给药结束后不同时间点的血标本,用高效液相色谱分析方法检测血清药物浓度.采用非线性混合效应模型法建立万古霉素PPK模型.结果 患者70例,男58例,女12例;年龄23~91岁,平均78岁;急性生理学及慢性健康状况评分(APACHⅡ)平均为(16.4±4.8)分.检测万古霉素血清药物浓度标本267份.万古霉素的血药浓度-时间数据符合二室模型;NONMEM法建立万古霉素PPK的最终模型为CLi=1.67×eη1,V1i=33.04×[1-0.199×(60/Scr)]×eη2,Qi=7.08×2.053AI×eη3,V2i=19.29×eη4.其中CLi、V1i、Qi和V2i分别指个体万古霉素的清除率、中央隔室表观分布容积、药物中央隔室与周边隔室的转换速率、周边隔室的表观分布容积;群体典型值分别为1.7 L/h、33.0 L、7.08 L/h、19.29 L.血肌酐中位值每变化1个单位,V1的校正幅度为19.9%;输入白蛋白患者的Q值为未输入白蛋白患者的2.1倍.结论 重症下呼吸道感染的患者血清肌酐水平和白蛋白水平是影响万古霉素PPK的因素.肾功能障碍可导致药物清除半衰期延长,应调整给药方案.输注白蛋白不影响万古霉素给药方案,但低蛋白血症患者输注白蛋白可能缩短药物到达肺组织的时间.

abstractsObjective To develop a population pharmacokinetic ( PPK) model of vancomycin in Chinese inpatients with severe lower respiratory tract infection .Methods We gathered serum concentrations of vancomycin from inpatients who received vancomycin during Nov 2011 to Nov 2012.Vancomycin serum concentrations was measured by high performance liquid chromatography .Vancomycin PPK analysis was performed using nonlinear mixed effects model (NONMEM) program.Results We gathered the data of 70 inpatients with lower respiratory tract infection at respiratory ward or respiratory intensive care unit ( RICU ) between Nov 2011 to Nov 2012 [58 males,12 females;78(23-91) years old;the mean of APACHⅡscore was 16.4 ±4.8 ] .A total of 267 concentrations of vancomycin were gathered from 70 patients. A 2-compartment model fit the concentration data best .The final vancomycin PPK model was: CLi =1.67 × eη1,V1i =33.04 ×[1 -0.199 ×(60/Scr)] ×eη2,Qi =7.08 ×2.053AI ×eη3,V2i =19.29 ×eη4.(CL:vancomycin clearance;V1:distribution volume of the central compartment; Q:intercompartment clearance;V2:distribution volume of the intercompartment ) .The population mean values were 1.67 L/h, 33.04 L;7.08 L/h and 19.29 L respectively.Serum creatinine was the covariate to affect vancomycin apparent distribution volume of the central compartment . Intercompartment clearance was 2.053 times larger in patients with albumin infusion than that in patients without .Conclusions We found that a 2-compartment model fit the concentration data best in Chinese patients with severe lower respiratory tract infection .Serum creatinine and albumin infusion were the most significant covariates to affect vancomycin PK .