蒙特卡洛模拟方法优化异烟肼临床最佳给药方案  

Monte Carlo simulation method to optimize Clinical Dosing Regimen of Isoniazid

作　　者：李君霞[1] 陈爽[1] 赵丽玲 郭蕊[1] 杨海鹏[1] 赵唯炜[1] LI Jun-xia;CHEN Shuang;ZHAO Li-ling;GUO Rui;YANG Hai-peng;ZHAO Wei-wei(Department of Pharmacy,Henan Provincial Chest Hospital,Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]河南省胸科医院,郑州大学附属胸科医院药学部,郑州450000

出　　处：《医药论坛杂志》2022年第23期7-10,共4页Journal of Medical Forum

基　　金：河南省医学科技攻关计划项目(2018020561)。

摘　　要：目的通过对一线抗结核药物异烟肼不同给药方案进行蒙特卡洛模拟,累积反应分数(CFR)>90%的给药方案是提高抗菌药物疗效的合理选择,以CFR与成本-效果分析来确定异烟肼的最佳给药方案。方法检索异烟肼对于结核分枝杆菌的最低抑菌浓度值(MIC)并结合药动学参数研究,求算给药后的AUC/MIC(AUIC)值。通过蒙特卡洛模拟不同给药方案的药效学关系,为临床结核患者的治疗方案提供更有利的数据支撑。结果异烟肼给药方案为300 mg qd po(300 mg,1次/d,口服)、400 mg qd po、600 mg tiw po(600 mg,1周3次,口服)时,其t1/2分别为(2.32±0.95)h、(2.24±0.96)h、(3.10±0.95)h;Cmax分别为(6.1±1.52)mg/(h·L)、(8.04±3.65)mg/L、(11.30±3.00)mg/L;AUC0-t分别为(27.98±14.50)mg/(h·L)、(35.27±18.28)mg/(h·L)、(41.10±13.45)mg/(h·L)。异烟肼对于结核分枝杆菌的最低抑菌浓度值(MIC)为0.25μg/mL,结合药动药效学(PK/PD)的蒙特卡洛模拟显示,300 mg qd po、400 mg qd po、600 mg tiw po的给药方案,异烟肼对结核分枝杆菌的药效学累计反应分数(CFR)均能达到90%以上,分别为96.19%、98.57%、100%。结论基于异烟肼的抗菌作用和临床疗效,为降低耐药性和不良反应的发生,同时提高患者的用药依从性,减轻患者的医疗负担,建议300 mg qd po为异烟肼最佳给药方案。Objective Through Monte Carlo simulation of the different dosing schedules of the first-line anti-tuberculosis drug Isoniazid,a dosing schedule with a cumulative fraction of response(CFR)>90%is selected as a reasonable choice for anti-tuberculosis empirical therapy,and combine the CFR with cost-effectiveness to determine the best dosing regimen for isoniazid.Methods The minimum inhibitory concentration(MIC)of isoniazid against Mycobacterium tuberculosis was retrieved and combined with the pharmacokinetic parameters,the AUC/MIC(AUIC)was calculated.Through Monte Carlo simulation of the pharmacodynamic relationship of different dosing regimens,it provides more favorable data support for tuberculosis patients.Results When the isoniazid dosing regimen was 300 mg qd po、400 mg qd po、600 mg tiw po,the t1/2 were(2.32±0.95)h,(2.24±0.96)h,(3.10±0.95)h,respectively;Cmax were(6.19±1.52)mg/(h·L),(8.04±3.65)mg/L,(11.30±3.00)mg/L;AUC0-t were(27.98±14.50)mg/(h·L),(35.27±18.28)mg/(h·L),(41.10±13.45)mg/(h·L),respectively.The minimum inhibitory concentration(MIC)of isoniazid for Mycobacterium tuberculosis was 0.25μg/mL,combined with pharmacokinetic pharmacodynamics(PK/PD),Monte Carlo simulation shows that 96.19%,98.57%,100%of the patients treated with isoniazid using the three dosage regiments attained a good pharmacodynamic target,respectively.Conclusion Based on the antibacterial effect and clinical efficacy of Isoniazid,in order to reduce the occurrence of drug resistance,adverse reactions,the medical burden of patients,and improve the medication compliance of patients,300 mg qd po is considered as the best dosing regimen of isoniazid.

关 键 词：结核 蒙特卡洛 异烟肼 药效学 

分 类 号：R914.1[医药卫生—药物化学]