利巴韦林用于慢性丙型肝炎病毒感染者的群体药动学文献分析  

Population pharmacokinetics literature analysis of ribavirin in patients with chronic hepatitis C virus infection

作　　者：李国兴 舒家华 陈松 向秋林[1,2] 余娴 LI Guo-xing;SHU Jia-hua;CHEN Song;XIANG Qiu-lin;YU Xian(College of Pharmacy,Chongqing Medical University,Chongqing 400016;Department of Phase I Clinical Trial Center,The Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010)

机构地区：[1]重庆医科大学药学院,重庆400016 [2]重庆医科大学附属第二医院Ⅰ期临床试验中心,重庆400010

出　　处：《中南药学》2022年第12期2925-2930,共6页Central South Pharmacy

基　　金：重庆医科大学附属第二医院“宽仁英才”项目基金(No.kryc-gg-2209)。

摘　　要：目的为利巴韦林用于慢性丙型肝炎病毒感染治疗的临床合理用药及个体化治疗提供参考。方法检索PubMed、Embase、CNKI、万方等数据库中发表的利巴韦林的群体药动学相关文献,总结其研究特征、模型特征,分析协变量对利巴韦林CL/F的影响。结果共纳入9篇文献,研究人群为18~81岁的慢性丙型肝炎病毒感染者;利巴韦林药动学特征符合二室或三室模型;CL/F典型值范围为13.1~21.5 L·h^(-1);显著影响利巴韦林CL/F的协变量有:性别、体质量、肾功能以及ITPA基因多态性。女性患者相较于男性患者CL/F较低;体质量越大的患者表现出更高的CL/F;肾功能受损的患者CL/F降低;与野生型患者相比ITPA基因变异型患者的CL/F较低。结论利巴韦林用于慢性丙型肝炎病毒感染者的临床用药方案需要考虑的因素包括性别、体质量、肾功能以及ITPA基因多态性,仍需更多研究来考察这些因素对利巴韦林药动学参数的影响。Objective To provide reference for the rational administration and individualized therapy of ribavirin for chronic hepatitis C virus infection.Methods Literatures related to population pharmacokinetics of ribavirin in PubMed,Embase,CNKI and WanFang Data were searched.The study characteristics and model characteristics were summarized,and the influence of covariates on ribavirin CL/F was analyzed.Results Totally 9 literatures were included.The study population was 18 to 81 years old patients with chronic hepatitis C virus infection.The pharmacokinetic characteristics of ribavirin fit the two-compartment or three-compartment model.The typical values of CL/F range from 13.1 to 21.5 L·h^(-1).The covariates that greatly affected ribavirin CL/F included gender,body mass,renal function and ITPA gene polymorphism.Female patients had lower CL/F than male patients;heavier patients showed higher CL/F;patients with impaired renal function had lower CL/F,while patients with ITPA genotype variants had lower CL/F than patients with wild-type.Conclusion Factors to be considered in the clinical dosing regimen of ribavirin for patients with chronic hepatitis C virus infection include gender,body mass,renal function,and ITPA gene polymorphism.More studies are needed to detemine the effect of population factors on the pharmacokinetic parameters of ribavirin.

关 键 词：利巴韦林 慢性丙型肝炎病毒感染 群体药动学 表观清除率 影响因素 

分 类 号：R969.3[医药卫生—药理学]