摘要
目的通过测定美罗培南优化两步点滴法两种点滴模型的药代动力学参数/药效动力学(PK/PD)参数,比较不同点滴方法的优劣。方法收集中、重度细菌性下呼吸道感染患者20例,随机分为实验组和对照组各10例。实验组和对照组分别按0.5 h/250 mg+2.5 h/750 mg和0.5 h/500 mg+2.5 h/500 mg的点滴模型给药;使用高效液相色谱内标法测定患者的药物浓度,使用Winnonlin求出实验组和对照组的美罗培南的血浆清除率(CL),表观分布容积(Vd),清除半衰期(t1/2),峰浓度(Cmax),达峰时间(Tmax),曲线下面积(AUC)等药代动力学参数;使用Crystal Ball软件按PK/PD模型进行蒙特卡罗模拟(MCS)计算Cmax/MIC、%T>MIC的比值及达标概率(PTAs),比较两种点滴方法的差异和优劣。结果实验组的Vd为35.51±3.33,t1/2为1.59±0.26,CL为14.80±1.11,Tmax为1.48±0.12,Cmax为11.86±0.54,AUC为64.40±4.62,对照组的Vd为29.13±4.21,t1/2为1.32±0.34,CL为14.41±1.76,Tmax为1.95±0.11,Cmax为15.25±0.93,AUC为64.56±7.38;在MIC分别为1、2、4μg/ml时,实验组的Cmax/MIC为6.40±0.55,3.20±0.27,1.60±0.14,%T>MIC为118.94±9.71,97.13±7.20,74.28±4.77,PTAs都为100%,而对照组的Cmax/MIC为15.46±1.97,7.71±0.98,3.87±0.49,%T>MIC为105.70±13.92,87.29±10.60,68.58±7.29,PTAs都为100%。结论实验组比对照组的Cmax/MIC小,但实验组的%T>MIC大于对照组,两组的达标概率都为100%,结果显示可能实验组要优于对照组,在临床上可以采用0.5 h/250 mg+2.5 h/750 mg的点滴方法抗感染。
Objective To determine the parameters of pharmacokinetics and pharmacodynamics（ PK/ PD） of different infusion models in optimized two-step infusion therapy of meropenem, then to compare the efficacy of two infusion method. Method 20 clinical mild, severe bacterial lower respiratory tract infection were collected, they were completely randomized into experimental group and control group with 10 cases in each group, the experimental group was infused with 0.5 h/250 mg ＋ 2.5 h/750 mg infusion model, and the control group was infused with 0.5 h/500 mg ＋ 2.5 h/500 mg infusion model; the plasma concentration of the patients were determined by using high performance liquid chromatographic internal standard method, the pharmacokinetics of meropenem, such as plasma clearance （CL）, the apparent volume of distribution （Vd）, the elimination half-life （tj/2 ）, peak concentration （Cmax）, time to peak （Tmax） , the area under the curve （AUC） and other pharmacokinetic parameters, were obtained by Winnonlin software with the measured plasma concentration-time profiles; using Crystal Ball software to perform Monte Carlo simulation （MCS） in order to calculate Cmax/MIC, % T 〉 MIC and PTAs according to the PK/PD model, then to compare the effect of two infusion models. Results Vd of the experimental group was 35.51±3.33, t1/2 was 1.59 ± 0.26, CL was 14.80 ± 1.11, Tmax was 1.48± 0.12, Cmax was 11.86±0.54, AUC was 64.40 ± 4.62, Vd of the control group was 29.13±4.21, tl/2 was 1.32±0.34, CL was 14.41 ±1.76, Tmax was 1.95± 0.11, Cmax was 15.25±0.93, AUC was 64.56±7.38 ; in MIC were 1,2, 4μg/ml, Cmax/MIC of the experimental group were 6.40±0.55, 3.20 ± 0.27, 1.60 ＋ 0.14, respectively; % T 〉 MICwere 118.94 ± 9.71, 97.13±7.20, 74.28±4.77, respectively; PTAs were all 100% ; Cmax/MIC of the control group were 15.46±1.97, 7.71±0.98, 3.87±0.49, respectively; %T 〉MIC were 105.70±13.92, 87. 29 ± 10.60, 68.58 ±7.29, respectively; PTAs were all 100%. Conclusions Cmax/MIC of the experimental group was smaller than the control group, but % T 〉 MIC of the experimental group was great than the control group , the PTAs of two groups were all 100%, the results revealed that the experimental group might be superior to the control group, the infusion model of 0.5 h/250 mg＋ 2.5 h/750 mg can be used in clinical to treat infeetion.
出处
《中华肺部疾病杂志（电子版）》
CAS
2013年第6期20-24,共5页
Chinese Journal of Lung Diseases(Electronic Edition)
基金
国家自然科学基金(青年)(81301662)
关键词
美罗培南
优化两步点滴法
蒙特卡罗模拟
Meropenem
Optimized two-step infusion therapy
Monte Carlo simulation
