应用蒙特卡罗模拟评估及优化脓毒症患者临床阿米卡星的给药剂量

Use of Monte Carlo Simulation to Evaluate and Optimize the Dosage Regimen of Amikacin in Patients with Sepsis

目的采用蒙特卡罗模拟的方法,以抗菌药物PK/PD理论为基础,评价与优化脓毒症患者阿米卡星的给药剂量。方法收集国内外已发表的阿米卡星的药代动力学资料和提取我院阿米卡星对革兰阴性杆菌的MIC分布数据;利用Cristal Ball软件模拟出10000例患者的目标获得概率(PTA)和累计反应分数(CRF)。结果对于脓毒症患者阿米卡星说明书推荐的给药剂量未能达到满意抗菌活性。结论蒙特卡罗模拟法把药代动力学参数和药效学数据结合起来,既考虑了不同个体对药物处置的差异性,又考虑了病原菌耐药性的差异,推荐的给药方案更能实现个体化给药目标,提高临床治疗效果,减少细菌耐药。

OBJECTIVE According to the PK/PD theory of antibiotics,Monte Carlo simulation was used to evaluate and optimize the administration regimen of amikacin in patients with sepsis.METHODS The pharmacokinetic data of amikacin published at home and abroad were collected and the MIC distribution data of amikacin against Gram-negative bacilli in our hospital were extracted.The Cristal Ball software was used to simulate the probability of goal attainment(PTA)and cumulative response fraction(CRF)in 10000 patients.RESULTS The recommended dose of amikacin for sepsis patients failed to achieve satisfactory antibacterial activity.CONCLUSION Monte Carlo simulation method combines pharmacokinetic parameters with pharmacodynamic data,which not only considers the difference of drug disposal among different individuals,but also considers the difference of drug resistance of pathogenic bacteria.The recommended dosage regimen can better achieve the goal of individualized administration,improve the clinical treatment effect and reduce bacterial resistance.