种族对移植患者他克莫司药动学的影响

摘要

目的:考察口服他克莫司在不同种族移植患者群体中的药动学差异,建立他克莫司药动学模型,为制订他克莫司用于不同移植群体的个体化治疗方案提供科学依据.方法:检索PubMed与万方数据库中关于口服他克莫司药动学的文献,从文献中提取该药在移植患者中的药动学数据,采用非线性混合效应模型(NONMEM)法对获得数据进行统计分析,建立群体药动学模型,并对模型进行图形评价和Bootstrap法验证.结果:他克莫司在移植患者中的群体药动学过程符合一室模型.他克莫司在黄种人中表观清除率(CL/F)为15.7 L/h,高于白种人(11.1 L/h).他克莫司清除率群体药动学模型为:CL=[15.7×Race+11.1×(1一Race)]×(Dose/10)0116.结论:种族因素会影响移植患者他克莫司的药动学过程.%OBJECTIVE:To investigate the population pharmacokinetics of the oral tacrolimus among transplant recipients of different ethnic background,to establish pharmacokinetics model of tacrolimus and provide scientific reference for individual therapy scheme of tacrolimus in different transplant recipients.METHODS:The literatures about the pharmacokinetics of tacrolimus were retrieved from PubMed and Wangfang database,and related pharmacokinetics data of transplant recipients were collected from published clinical trials literatures.Nonlinear mixed effects model(NONMEM) was used to analyze the collected data statistically to establish population pharmacokinetics model.Pattern evaluation and Bootstrap validation of model were conducted.RESULTS:The population pharmacokinetics of tacrolimus was in line with one-compartment model.The apparent clearance (CL/F) of tacrolimus was lower in the Caucasian subjects (11.1 L/h) than in the Asian subjects (15.7 L/h).The population pharmacokinetics of apparent clearance of tacrolimus:CL=[15.7 × Race+1 1.1× (1-Race)]× (Dose/10)0.116.CONCLUSIONS:Population pharmacokinetics of tacrolimus can be affected by race.