多黏菌素B在脓毒症患者中的药动学研究  

Pharmacokinetics Study of Polymyxin B in Patients with Sepsis

作　　者：张俊[1] 周霖[1] 郑天元 罗永刚[2] 孙志[1] ZHANG Jun;ZHOU Lin;ZHENG Tianyuan;LUO Yonggang;SUN Zhi(Department of Pharmacy,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China;Department of Neurosurgery Intensive Care Unit,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学第一附属医院药学部,郑州450000 [2]郑州大学第一附属医院神经外科ICU,郑州450000

出　　处：《中国药学杂志》2024年第15期1424-1428,共5页Chinese Pharmaceutical Journal

基　　金：中青年科技创新杰青人才项目资助(YXKC2021042);河南省医学科技攻关省部共建重点项目资助(SBGJ202102081);河南省科技攻关项目资助(242102311040);河南省自然科学基金项目资助(242300420384)。

摘　　要：目的研究多黏菌素B(polymyxin B,PB)在脓毒症患者中的药动学,为该药的临床合理应用提供依据。方法脓毒症患者静脉给予PB,q12 h,连续给药4剂,分别于各剂给药前及第5剂给药后0.5、1、2、3、6、9、12 h采集血样,采用超高效液相色谱串联质谱(ultra-high performance liquid chromatography-tandem mass spectrometry,UHPLC-MS/MS)分析方法测定PB血浆浓度。采用非房室模型方法计算主要的药动学参数,以稀疏血药浓度数据点建立有限采样模型。结果最终纳入18例患者,PB的主要药动学参数0~24 h血药浓度-时间曲线下面积(AUC_(0-24 h))为(63.33±30.88)mg·h·L^(-1),第5剂给药前血药浓度(ρ_(0))为(2.01±1.54)mg·L^(-1),第5剂给药后的峰浓度(ρ_(max))为(6.90±4.22)mg·L^(-1),第5剂给药后12 h血药浓度(ρ_(12))为(1.64±1.04)L·h^(-1),平均稳态血药浓度(ρ_(ss,av))为(2.64±1.29)mg·L^(-1),第一剂、第二剂、第三剂给药后的谷浓度分别为(3.35±2.50),(2.74±1.60),(1.76±1.10)mg·L^(-1)。推荐2点回归方程为:AUC_(0-12 h)=2.08+1.22ρ_(1)+9.41ρ_(6)。结论PB在脓毒症患者体内的药动学参数存在个体差异,首剂给予负荷剂量可很快达到稳态浓度,给药后1、6 h的PB浓度点可用于估算AUC_(0-24 h),建议监测PB-AUC_(0-24 h)值调整成人脓毒症患者的给药剂量。OBJECTIVE To study the pharmacokinetics of polymyxin B(PB)in sepsis patients and to provide evidence for its rational clinical use.METHODS Sepsis patients were given intravenous PB,every 12 h(q12 h),4 consecutive doses.Blood samples were collected before each dose and 0.5,1,2,3,6,9,12 h after the fifth dose.The plasma concentrations of PB were determined by UHPLC-MS/MS method.The main pharmacokinetic parameters were calculated by non-compartment model,and a limited sampling model was established with sparse blood concentration data points.RESULTS A total of 18 patients were included.The main pharmacokinetic parameters of PB were as follows:area under the concentration-time curve for the 24 h exposure after the fifth dose(AUC_(0-24 h))was(63.33±30.88)mg·h·L~(-1),plasma concentrations prior to the fifth dose(ρ_0)was(2.01±1.54)mg·L~(-1),post the fifth dose peak plasma concentration(ρ_(max))was(6.90±4.22)mg·L~(-1),plasma concentrations of 12 h after the fifth dose(ρ_(12))was(1.64±1.04)mg·L~(-1),average steady-state plasma concentration(ρ_(ss,av))was(2.64±1.29)mg·L~(-1),trough concentrations after the first,second and third doses were(3.35±2.50)(2.74±1.60)and(1.76±1.10)mg·L~(-1),respectively.The recommended two-point regression equation is AUC_(0-12 h)=2.08+1.22ρ_1+9.41ρ_6.CONCLUSIONS There are individual variabilities in the pharmacokinetic parameters of PB in patients with sepsis.The loading dose of the first dose can reach the steady-state concentration as soon as possible,and the PB concentration point 1,6 h after administration can be used to estimate AUC_(0-24 h).It is suggested to monitor PB-AUC_(0-24 h)to guide the adjustment of PB dosage in adult patients with sepsis.

关 键 词：多黏菌素B 脓毒症 药动学 有限采样法 超高效液相色谱串联质谱 

分 类 号：R969.1[医药卫生—药理学]