辛伐他汀在年轻健康受试者中的群体药动学研究  

Population Pharmacokinetics Study of Simvastatin in Young Healthy Volunteers

作　　者：朱立勤[1] 章袁[2] 季双敏[3] 庄艳楠[4] 陈敬国[4] 

机构地区：[1]天津市第一中心医院,天津300192 [2]天津医科大学,天津300070 [3]北京大学医学部,北京100191 [4]天津中医药大学,天津300193

出　　处：《中国药房》2013年第10期915-917,共3页China Pharmacy

摘　　要：目的:考察口服辛伐他汀在年轻健康受试者体内的群体药动学模型。方法:利用中国知网(CNKI)、万方数据库、维普数据库、PubMed电子检索系统等收集与辛伐他汀药动学相关的文献共29篇,以文中涉及到的474名年轻健康受试者为研究对象,运用非线性混合效应模型(NONMEM)建立辛伐他汀的药动学模型。考察年龄、体质量、身高等对药动学参数的影响,并以Bootstrap法进行模型验证。结果:本研究建立了年轻人群口服辛伐他汀一级吸收和消除的一房室药动学模型。体内的辛伐他汀表观清除率(CL/F)、表观分布容积(V/F)和口服吸收系数(Ka)的群体典型值分别为1630L/h、4320L、1.46h-1;年龄、体质量、身高等因素加入模型之后,基本模型并未有明显改善(P>0.05)。结论:年轻人群CL/F和V/F值高于文献中的老年人群值。OBJECTIVE： To investigate the population pharmacokinetics （PPK） model of simvastatin in young healthy volunteers with oral administration. METHODS： 474 young healthy volunteers in 29 literatures of simvastatin literatures retrieved from CNKI, Wanfang database, VIP, PubMed were chosen as research object. Nonlinear mixed effect modeling （NONMEM） was employed to establish the PPK model of simvastatin. The fixed effects including age, weight, height on pharmacokinetic parameters of PPK were estimated. The final PPK model was validated by Bootstrap method. RESULTS： One-compartment models with first-or-der absorption and elimination were built. The typical population values, such as CL/F, V/F and K,, were 1 630 L/h, 4 320 L and 1.46 h^-1 in youngers. The basic model couldn＇t be improved after involved the fixed effects, such as age, weight, height （P〉 0.05）. CONCLUSIONS： CL/F and V/F of the youngers are higher than those of the elders from literature.

关 键 词：辛伐他汀 年轻受试者 非线性混合效应模型 群体药动学 

分 类 号：R969.1[医药卫生—药理学] R972.6[医药卫生—药学]