Evaluation of ceftriaxone dosing regimens based on PK/PD models and Monte Carlo simulations  

基于PK/PD模型和蒙特卡洛模拟评价头孢曲松给药方案

作　　者：Ye Yuan Yanan Li Qing Zhao Bo Yu Xiuling Yang 袁叶;李亚男;赵晴;于博;杨秀岭(河北医科大学第二医院,河北石家庄050000)

机构地区：[1]The Second Hospital of Hebei Medical University,Shijiazhuang 050000,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2022年第5期382-388,共7页中国药学（英文版）

基　　金：2019 Second Hospital of Hebei Medical University Pro ject(Grant No.2h2019042)。

摘　　要：In the present study,we optimized the ceftriaxone dosing regimens based on pharmacokinetic/pharmacodynamic(PK/PD)principles using Monte Carlo simulation(MCS).Based on PK/PD theory,MCS was performed using Crystal Ball software combining PK and PD parameters with 10000 simulation runs to calculate the probability of target attainment(PTA)and cumulative fraction of response(CFR)for the seven clinically common dosing regimens of ceftriaxone(1 g qd,1.5 g qd,1 g bid,2 g qd,1 g tid,1.5 g bid,and 2 g bid).A%fT≥50 as the target value expected to achieve satisfactory clinical efficacy and a dosing regimen with an obtained CFR≥90%or the ability to achieve the highest PTA was used as a reasonable choice for empirical antimicrobial therapy,i.e.the clinically optimal regimen.All eight pathogenic bacteria had a CFR>90%when the dosing regimen was 2 g bid and 1 g tid,seven pathogenic bacteria had a CFR>90%when the dosing regimen was 1 g bid and 1.5 g bid,except for Pseudomonas aeruginosa,and all pathogenic bacteria had a CFR<90%when the dosing regimen was 1 g qd and 1.5 g qd.The dosing regimens of 2 g bid and 1 g tid were effective against all eight pathogenic bacteria infections,and 1 g bid and 1.5 g bid dosing regimens were effective against the other seven pathogenic bacteria except for Pseudomonas aeruginosa.依据药动/药效(PK/PD)原理,应用蒙特卡洛模拟优化头孢曲松的给药方案。基于PK/PD理论,使用水晶球软件将药动学和药效学参数结合,进行蒙特卡洛模拟,模拟运行次数为10000次,计算头孢曲松的临床常用7种给药方案(1 g qd、1.5 g qd、1 g bid、2 g qd、1 g tid、1.5 g bid、2 g bid)的达标概率(probability of target attainment,PTA)及累积反应分数(cumulative fraction of response,CFR)。以%fT≥50作为预期可获得满意临床疗效的靶值,并经获得的CFR≥90%或者能达到最高PTA的给药方案作为抗菌药物经验治疗的合理选择,即临床最佳治疗方案。给药方案为2 g bid和1 g tid时,8种致病菌均CFR>90%;给药方案为1 g bid和1.5 g bid时,除铜绿假单胞菌外,其他7种致病菌CFR>90%;当给药方案为qd时,所有致病菌的CFR<90%。头孢曲松2g bid和1 g tid给药方案对8种致病菌的感染均有效,1 g bid和1.5 g bid给药方案,对除铜绿假单胞菌外的其他7种致病菌有效。

关 键 词：CEFTRIAXONE PK/PD Monte Carlo simulation Antibacterial drugs Clinical efficacy 

分 类 号：R969[医药卫生—药理学]