美罗培南在脓毒血症患者体内的药动学研究

Study on pharmacokinetics of meropenem in patients with sepsis

目的探讨美罗培南在脓毒血症患者体内的药动学研究。方法选择2015年7月至2016年8月上海交通大学医学院附属新华医院急诊重症监护病房收治的脓毒血症患者13例。所有患者均静脉匀速滴注美罗培南0.5～1.0 g，给药后5 min和6 h抽取血样，将血液离心后取血浆200 μl，采用高效液相色谱法测定血浆中美罗培南血药浓度，采用肌酐亚胺水解酶法测定肌酐浓度，并比较脓毒血症患者与参考文献中健康受试者美罗培南药动学参数。结果13例患者静脉滴注美罗培南后，给药后5 min中位血药浓度为33.09（15.46,57.39）mg/L； 给药后6 h中位血药浓度为2.10（0.28，15.94）mg/L。 13例脓毒血症患者肌酐清除率为88（50,205）L/h。美罗培南在脓毒血症患者中的主要药动学参数包括：中位最大血药浓度（Cmax）/剂量为40（25,66） mg/（L·g）；中位半衰期（t1/2）为 2.21（0.74,3.57） h；中位清除率（CL）为7.5（5.2,10.9） L/h；中位表观分布容积（V）为9.3（9.2,10.9）L；中位速率常数（K12）为2.0（1.8,2.2）/h；中位K10为0.8（0.6,1.1）/h。脓毒血症患者Cmax/剂量、t1/2、CL和V均低于文献中健康受试者［（36 mg/（L·g）、0.97 h、11.7 L/h、18.6 L］。结论美罗培南在脓毒血症患者体内的主要药动学参数Cmax/剂量、t1/2、CL、V与文献报道健康受试者有较大差异，需要对使用美罗培南脓毒血症患者进行血药浓度监测。

ObjectiveTo explore pharmacokinetic parameters of meropenem in patients with sepsis. MethodsThirteen patients with sepsis from July 2015 to August 2016 in Emergency Intensive Care Unit, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled. All patients had meropenem（0.5-1.0 g） intravenous drip infusion. Plasma concentration of meropenem was detected by high performance liquid chromatography; concentration of plasma creatinine was detected by creatinine imine enzymatic hydrolysate method. Pharmacokinetic parameters was compared between sepsis patients and healthy people. ResultsPlasma concentration of meropenem 5 min after drug administration in 13 patients was 33.09（15.46,57.39）mg/L; plasma concentration of meropenem 6 h after drug administration was 2.10 （0.28,15.94）mg/L. Creatinine clearance rate in 13 patients was 88（50, 205）L/h. The maximum concentration of meropenem（Cmax）/dosage was 40（25, 66）mg/（L·g）; median half-life （t1/2）=2.21（0.74, 3.57） h, median clearance rate （CL）=7.5（5.2, 10.9）L/h; median apparent volume of distribution （V）=9.3（9.2, 10.9）L; median rate constant （K12）=2.0（1.8, 2.2）, median rate constant K10=0.8（0.6, 1.1）. Cmax/dosage, t1/2, CL and V in patients with sepsis were lower than those in healthy people[36 mg/（L·g）, 0.97 h, 11.7 L/h, 18.6 L]. ConclusionsPharmacokinetic parameters of meropenem in patients with sepsis are different from those in healthy people.