基于药动学/药效学模型和蒙特卡罗模拟评价肝功能不全患者念珠菌感染时米卡芬净的给药方案

Evaluation of dosage regimen of micafungin against Candida infection in patients with hepatic dysfunction based on PK/PD analysis and Monte Carlo simulation

目的基于药动学/药效学(PK/PD)模型和蒙特卡罗模拟优化不同肝功能患者在念珠菌感染时米卡芬净的给药方案。方法根据已发表的米卡芬净PK参数和念珠菌药敏数据,应用蒙特卡罗模拟获取不同肝功能患者的达标概率及累积反应分数。结果对于不同肝功能患者,米卡芬净在给药剂量为100 mg/d时对热带念珠菌效果良好,对光滑念珠菌、克鲁斯念珠菌、近平滑念珠菌效果较差,对白念珠菌效果受患者肝功能的影响较大,在肝功能正常患者中效果较好,当患者存在中度及重度肝功能不全时治疗效果较差。结论对于不同类型的念珠菌以及不同程度肝功能不全患者,应考虑调整米卡芬净的剂量。

Objective To optimize the dosage regimen of micafungin in patients with hepatic function based on pharmacokinetic/pharmacodynamic(PK/PD)analysis and Monte Carlo simulation.Methods PK parameters and antimicrobial susceptibility data against Candida isolates were collected about micafungin.Patients with hepatic dysfunction were analyzed by Monte Carlo simulation(Crystal Ball)to calculate probability of target attainment and cumulative fraction of response.Results For patients with different hepatic functions,micafungin showed good efficacy against Candida tropicalis at dose of 100 mg/d,but poor effect on Candida glabrata,Candida krusei,and Candida parapsilosis.The therapeutic effect for C.albicans was largely affected by liver function.Micafungin has good effect in patients with normal liver function.The treatment effect is poor in case of moderate and severe liver insufficiency.Conclusions The dosage of micafungin should be adjusted targeting different Candida species in patients with hepatic dysfunction.