中国临床药理学杂志2013，Vol.29Issue(6)：429-432,436,5.
辛伐他汀在血液透析患者的群体药代动力学
Population pharmacokinetics study of simvastatin in hemodialysis patients
摘要
Abstract
Objective To investigate the population pharmacokinetic characteristics of simvastatin in hemodialysis patients and factors covariables that might impact its clearance.Methods The qualified maintenance hemodialysis patients took simvastatin 20 mg orally once and then 2 -4 serum samples were collected at different time.The serum simvastatin concentration was measured with the method of HPLC-MS/MS and analysed with nonlinear mixed-effect model (NONMEM).The population pharmacokinetics parameters were compared with those of healthy volunteers in literatures.Results A total of 23 patients took simvastatin and contributed 95 serum samples.There were eleven male cases.The mean age was 60.48 years.NONMEM demonstrated that the data were fit for two-compartment model.Typical population estimates (95％ confidence intervals) of CL1,CL2,V1,V2,Ka and Tlag were 663(375-951)L· h-1,197(42.7-351)L · h-1,119(32.2-206)L,1830(905-2760) L,0.59 (0.37-0.82) h-1,0.49 (0.48-0.50) h,respectively.Dialyzer,smoking,body mass index might impact the simvastatin clearance rate.The extrapolated pharmacokinetics parameters t1/2,Cmax,tmax,AUC0→t were (6.83 ± 10.79) h,(12.25 ± 8.35) μg · L-1,(0.90 ±0.27) h,(30.80 ±25.00) μg · h · L-1,respectively.Conclusion The population pharmacokinetic model of simvastatin by NONMEM was proved to be reliable.It might realize the simvastatin dosage individualation in hemodialysis patients.This study demonstrated that the AUC with simvastatin (20 mg) was similar to that of healthy volunteers with simvastatin 40 mg orally in literatures.It recommends that simvastatin should be administered individully and less legular initial dose might be used in hemodialysis patients.关键词
辛伐他汀/群体药代动力学/血液透析患者Key words
simvastatin/ population pharmacokinetics/ hemodialysis patients分类
医药卫生引用本文复制引用
杨文领,张现化,闵青,邵雪岩,王思媛,尚德为,田信奎,庄震,朱宁..辛伐他汀在血液透析患者的群体药代动力学[J].中国临床药理学杂志,2013,29(6):429-432,436,5.基金项目
中华医学会动脉粥样硬化临床医学科研专项资金项目(09010030158) （09010030158）
北京大学第三医院种子基金(2008年) （2008年）
