阿托伐他汀在健康受试者中的群体药动学研究

Population pharmacokinetics study of atorvastatin in healthy volunteers

目的建立阿托伐他汀在健康受试者中的群体药动学模型,预测其在健康人群中群体药动学特征,为临床合理用药提供依据。方法计算机检索中国期刊全文数据库(CNKI)、中文科技期刊全文数据库维普(VIP)和万方数字化期刊全文库、Pub Med电子检索系统和美国医学文摘数据库(Medline),提取阿托伐他汀的血药浓度数据,运用非线性混合效应模型(NONMEM)法构建阿托伐他汀的群体药动学模型,考察其在健康受试者体内的群体典型值特征,并以Bootstrap法进行模型验证。结果筛选出11篇文献,共纳入394例受试群体。最终得到的群体药动学参数中表观清除率(Cl/F)和表观分布容积(V/F)的群体典型值分别为255 L/h、3 180 L。结论经Bootstrap验证,阿托伐他汀在健康受试者中的群体药动学模型稳定、可靠,所得参数稳定、可信度较好。

Objective To develop a population pharmacokinetics（PPK） model of atorvastatin for predicting the population pharmacokinetics features of atorvastatin in healthy volunteers, and to provide basis for rational use of atorvastatin. Methods China Journal Full-text Database（CNKI）, Chinese Science and Technology Journal Full-text Database（VIP）, Wanfang Database, Pub Med Electronic Retrieval System, American Medical Abstract Database（Medline）, etc were searched by computer. The blood concentration of atorvastatin in the literature were gained, then the PPK model of atorvastatin was constructed by nonlinear mixed effects model（NONMEM）, and the population typical characteristics effects in healthy volunteers was investigated. The PPK model was validated by Bootstrap method. Results A total of 11 studies were included, involving 394 volunteers. The typical population values of Cl/F and V/F in final PPK parameters were 255 L/h and 3 180 L. Conclusion Bootstrap validation confirms the stability and validity of the PPK model and parameters.