肝肾功能对利奈唑胺致血小板减少症发生的影响及基于群体药物代谢动力学的给药策略:meta分析及系统评价  

Effects of liver and kidney function on occurrence of linezolid-induced thrombocytopenia and administration strategies based on population pharmacokinetics:a meta-analysis and systematic review

作　　者：邓雅婷 丁亮 魏开兴 段紫云 岳耀辉 Deng Yating;Ding Liang;Wei Kaixing;Duan Ziyun;Yue Yaohui(Office of Pharmacology and Toxicology,Department of Basic Medicine,Xi′an Medical University,Xi′an 710021,China;Department of Pharmacy,Xi′an Chang′an Hospital,Xi′an 710613,China;Department of Pharmacy,Xi′an Pediatric Hospital,Xi′an 710003,China)

机构地区：[1]西安医学院基础医学部药理学与毒理学教研室,西安710021 [2]西安长安医院药剂科,西安710613 [3]西安市儿童医院药剂科,西安710003

出　　处：《药物不良反应杂志》2024年第6期337-346,共10页Adverse Drug Reactions Journal

基　　金：陕西省自然科学基础研究计划(2023-JC-YB-702)。

摘　　要：目的系统评价肝肾功能与利奈唑胺致血小板减少症(TP)风险的相关性及利奈唑胺的群体药物代谢动力学(PPK)特征,为肝肾功能不全患者利奈唑胺的个体化用药提供指导。方法检索国内外相关数据库中截至2023年11月肝肾功能不全与利奈唑胺致TP风险的相关文献,采用Rev Man 5.4统计软件进行meta分析,效应值为比值比(OR)和标准化均数差(SMD)及其95%置信区间(CI);对肝肾功能不全患者利奈唑胺的PPK研究文献进行汇总和系统评价。结果纳入meta分析的文献共32篇,包括4112例患者,其中TP患者1458例(35.5%),非TP患者2654例(64.5%)。meta分析结果显示,肾功能不全组利奈唑胺致TP的风险高于肾功能正常组[47.9%(594/1241)比25.8%(493/1912),OR=3.24,95%CI:2.31~4.53],较低的基线肌酐清除率(Ccr)和估算肾小球滤过率(eGFR)与利奈唑胺相关TP的发生风险有关(均P<0.05);肝功能不全组利奈唑胺致TP的风险高于肝功能正常组[47.6%(119/250)比33.9%(360/1061),OR=2.36,95%CI:1.73~3.22],较高的基线总胆红素(TBil)与利奈唑胺相关TP的发生风险有关(P<0.05)。纳入PPK研究的文献共15篇,其中11篇文献基于自建或公开发表的PPK模型,采用蒙特卡洛模拟不同给药方案的有效性和安全性概率,优化利奈唑胺的给药方案;5篇优化了肾功能不全患者利奈唑胺的给药方案,2篇优化了肝功能不全患者利奈唑胺的给药方案。结论肝肾功能不全增加了利奈唑胺致TP的风险,基线Ccr、eGFR和TBil水平可作为预测TP风险的敏感指标。肝肾功能不全患者在使用利奈唑胺治疗时可通过PPK模型优化利奈唑胺给药方案,减少TP的发生风险。Objective To systematically evaluate the effects of liver and kidney function on the occurrence of thrombocytopenia induced by linezolid and the population pharmacokinetic characteristics of linezolid,so as to provide guidance for the individualization of linezolid in patients with liver and renal insufficiency.Methods Relevant databases at home and abroad have been searched up to November 2023.The literature about the influence of liver and kidney function on linezolid-induced thrombocytopenia were analyzed using the Rev Man 5.4 statistical software,and the effect sizes were odds ratio(OR)and standardized mean difference(SMD)with their 95%confidence interval(CI)in the meta-analysis.The literature on population pharmacokinetic studies of linezolid were summarized and systematically reviewed.Results A total of 32 literature were included in the meta-analysis,including 4112 patients.Among them,1458(35.5%)developed thrombocytopenia and 2654(64.5%)did not.The meta-analysis results showed that the risk of linezolid-induced thrombocytopenia in the renal insufficiency patients was higher than that in patients with normal renal function[47.9%(594/1241)vs.25.8%(493/1912),OR=3.24,95%CI:2.31-4.53],and the lower baseline creatinine clearance(Ccr)and estimated glomerular filtration rate(eGFR)were associa-ted with the higher risk of linezolid-related thrombocytopenia(all P<0.05);the risk of thrombocytopenia induced by linezolid in patients with liver dysfunction was higher than that in patients with normal liver function[47.6%(119/250)vs.33.9%(360/1061),OR=2.36,95%CI:1.73-3.22],and the higher baseline total bilirubin(TBil)was associated with the higher risk of linezolid-related thrombocytopenia(all P<0.05).A total of 15 articles were included in the review of population pharmacokinetic study,11 of which were based on self-built or publicly published population pharmacokinetic models and used Monte Carlo simulation to evaluate the efficacy and safety probabilities in different dosing regimens of linezolid.Among them,there were

关 键 词：肾功能不全 肝功能不全 利奈唑胺 血小板减少症 META分析 系统评价 群体药物代谢动力学 剂量优化 

分 类 号：R969[医药卫生—药理学]