老年医学与保健2017，Vol.23Issue(6)：473-476,4.
基于计算机仿真模拟结果推荐老年人左奥硝唑给药方案
Dosage regime Optimization of Levornidazole for Elderly Based on Computational Simulation
摘要
Abstract
Objective To evaluate different dose regimens of levornidazole in healthy elderly through computational simulations and PK/PD analysis.Methods An single-center,open-label,single-dose study was conducted to investigate pharmacokinetic (PK) characteristics of single dose levornidazole for injection,500 mg,by intravenous drip infusion in healthy elderly.WinNonlin software was applied in simulating 7-day dosing regimens of 500 mg,q 12 h and 750 mg,q 24 h in the elderly and the pharmacokinetic parameters were observed;Monte Carlo simulation was used in estimating the probability of target attainment and cumulative fraction of response to Bacteroides fragilis of both dosing regimens under various MIC levels.Results The main pharmacokinetic parameters in the elderly over 65 years old after a single dose of 500 mg levornidazole were recorded as follows:Cmax:(11.97±1.16) μg/mL,AUC0-96:(171.24 ±20.43) μg·h/mL,AUC0-∞:(172.16 ±20.88) μg·h/mL,t1/2:(12.46 ± 1.85) h while those in the elderly after multi-dose regimens of 500 mg and 750 mg were as follows:Cmax:(20.6±1.9) μg/mLand (20.5-±-1.6) μg/mL respectively,AUC0-τ:(166.1±19.6) μg·h/mLand (251.0±29.6) μg·h/mL,t1/2:(11.8±1.9) h of both;the results of the Monte Carlo simulation showed that for both dose regimes of 750 mg,q 24 h and 500 mg,q 12 h to Bacteroides fragilis,the CFR for AUC0-24MIC＞ 157.6 and Cmax/MIC≥ 14.1 were over 96％,and the pharmacodynamic target value probability reached 100 ％ when the MIC ≤ 1 μg/mL.Conclusions Both of 500 mg,q 12 h and 750 mg q 24 h dose regimens of levornidazole are recommended for the treatment of anaerobic infection in elderly patients.关键词
老年人/左奥硝唑氯化钠注射液/药动学/计算机模拟/药动/药效学Key words
elderly/levornidazole and sodium chloride injection/pharmacokinetic/computational simulation/pharmacokinetics/pharmacodynamics (PK/PD)引用本文复制引用
李鑫,郭蓓宁,何高丽,曹国英,武晓捷,陈渊成,吴俊珍,张菁..基于计算机仿真模拟结果推荐老年人左奥硝唑给药方案[J].老年医学与保健,2017,23(6):473-476,4.基金项目
国家自然科学基金面上项目(81373494) （81373494）
