目的 建立阿托伐他汀在健康受試者中的群體藥動學模型,預測其在健康人群中群體藥動學特征,為臨床合理用藥提供依據(jù).方法 計算機檢索中國期刊全文數(shù)據(jù)庫(CNKI)、中文科技期刊全文數(shù)據(jù)庫維普(VIP)和萬方數(shù)字化期刊全文庫、PubMed 電子檢索系統(tǒng)和美國醫(yī)學文摘數(shù)據(jù)庫(Medline),提取阿托伐他汀的血藥濃度數(shù)據(jù),運用非線性混合效應模型(NONMEM)法構建阿托伐他汀的群體藥動學模型,考察其在健康受試者體內(nèi)的群體典型值特征,并以Bootstrap 法進行模型驗證.結果 篩選出11 篇文獻,共納入394 例受試群體.最終得到的群體藥動學參數(shù)中表觀清除率(Cl/F)和表觀分布容積(V/FF)的群體典型值分別為255 L/h、3 180 L.結論 經(jīng)Bootstrap 驗證,阿托伐他汀在健康受試者中的群體藥動學模型穩(wěn)定、可靠,所得參數(shù)穩(wěn)定、可信度較好.

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, PubMed 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/FF and V/FF 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.