健康志愿者多剂量服用六味地黄丸对CYP3A4活性的影响  

Effect of Multiple Doses of Liuwei Dihuang Pills on Activity of CYP3A4 in Healthy Volunteers

作　　者：裘福荣[1] 赵亚男[2] 孙华[2] 高成璐[1] 马越鸣[3] 蒋健[1] 

机构地区：[1]上海中医药大学附属曙光医院临床药理科,上海201203 [2]皖南医学院弋矶山医院,安徽芜湖241000 [3]上海中医药大学药代实验室,上海201203

出　　处：《中国药学杂志》2010年第13期983-986,共4页Chinese Pharmaceutical Journal

基　　金：国家"重大新药创制"科技重大专项新药临床评价研究技术平台项目(2008ZX09312);上海市教委重点学科中药临床药理学项目(No.J50303);上海市申康医院发展中心临床药理学科研共享平台项目(SHDC12007202)

摘　　要：目的在健康志愿者体内研究多剂量口服六味地黄丸对细胞色素P450(CYP)3A4活性的影响作用。方法采用随机开放两周期试验设计,8例健康志愿者口服六味地黄丸14d(每天3次,每次8粒)的前后单剂量口服咪达唑仑15mg,HPLC测定给药后咪达唑仑10h内的不同时间点的血浆浓度。结果口服六味地黄丸前与口服六味地黄丸14d后的咪达唑仑ρmax,AUC0-10,CL/F和t1/2比值的90%可信区间分别为(44.5,78.5)ng·mL-1,(58.9,85.8)ng.h.mL-1,(116.4,170.7)L.h-1和(88.1,124.9)h,口服六味地黄丸前后咪达唑仑tmax无明显差异。结论口服六味地黄丸14d对肠道CYP3A4有诱导作用。OBJECTIVE To examine the potential effect of Liuwei Dihuang pills on the CYP3A4 activity. METHODS In a sequential study with two phases, 8 volunteers were given 15 mg midazolam on day 1 and day 15. From day 2 to day 15 ,volunteers received Liuwei Dihuang pills three times daily, eight pills each time for 14 d. On day 15, they received Liuwei Dihuang pills with 15 mgmidazolam. The plasma concentrations of midazolam were measured on days 1 and 15 for 10 h. RESULTS The 90% confidence interval ofp AUC0-10, CL/F and t1/2of midazolam with 14 d Liuwei Dihuang pills vs. without comedication were （44. 5, 78. 5） ng · mL^-1, （58.9, 85.8） ng · h · mL ^-1, （116.4, 170.7） L · h ^-1 and （88. 1,124.9） h, respectively. The time to peak plasma mid- azolam concentration was unchanged by Liuwei Dihuang pills （P 〉 0. 05）. CONCLUSION Liuwei Dihuang pills could decrease absorption of midazolam by inducing CYP3A4 in gut.

关 键 词：六味地黄丸 咪达唑仑 药物相互作用 细胞色素P4503A4 

分 类 号：R969[医药卫生—药理学] R285.6[医药卫生—药学]