白杨黄素和柚皮素对沙奎那韦在大鼠体内药动学的影响  

Effects of Co-administration with Chrysin and Naringenin on the Pharmacokinetics of Saquinavir in Rats

作　　者：于小桐[1,2] 张敬茹[1,2] 孙宁[3] 秦一[3] 李佳朋 朱忱[3] 刘亦韦 顾健[1] 赵立波[3] 

机构地区：[1]北京大学人民医院药剂科,北京100044 [2]北京大学药学院药事管理与临床药学系,北京100191 [3]首都医科大学附属北京儿童医院药剂科,北京100045

出　　处：《中国药学杂志》2017年第15期1347-1351,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学青年基金资助项目(81102877)

摘　　要：目的探讨大鼠中白杨黄素和柚皮素与P-糖蛋白底物沙奎那韦同服时,对后者口服生物利用度及药动学的影响。方法将SD大鼠分为3组分别灌胃沙奎那韦(30 mg·kg^(-1))、沙奎那韦(30 mg·kg^(-1))+柚皮素(40 mg·kg^(-1))、沙奎那韦(30mg·kg^(-1))+白杨黄素(40 mg·kg^(-1)),采用LC-MS/MS测定给药后的血药浓度,计算药动学参数。结果沙奎那韦在沙奎那韦对照组,沙奎那韦+柚皮素组和沙奎那韦+白杨黄素组大鼠体内主要药动学参数分别为:AUC0-t,882.91,861.32,934.84ng·h·m L^(-1);AUC0-∞,903.97,865.90,947.92 ng·h·m L^(-1);ρmax,177.72,89.8,130.72 ng·m L^(-1);tmax,1,2,0.5 h;t1/2,11.73,12.61,13.33 h;MRT0-∞,27.09,31.63,26.60 h;CL/F,21.65,21.45,20.62 m L·kg^(-1)·h^(-1)。结论沙奎那韦的药时曲线存在双峰现象;柚皮素和白杨黄素对沙奎那韦的口服生物利用度和药动学参数没有显著性影响。OBJECTIVE To assess the impact of chrysin and naringenin on the pharmacokinetics （PK） of saquinavir （ SQV）, a substrate of P-glycoprotein （P-gp） , in rats. METHODS Fifteen rats were randomized into 3 groups of equal size, and administered orally 30 mg kg-1 SQV with or without 40 mg kg-1 chrysin or naringenin. The PK of SQV was assessed using non-compartmental analysis and the plasma concentrations of three groups were determined by LC-MS/MS. RESULTS The PK parameters values of SQV, SQV ＋ naringenin, SQV ＋ chrysin are as follows：AUC0-t ,882. 91,861.32,934. 84 ng h mL-1 ; AUC0-∞ ,903.97,865.90, 947.92 ng h mL-1; Pmax,177. 72,89. 8,130. 72 ng mL-1; tmax,1,2,0. 5 h;t1/2,11.73,12. 61,13.33 h; MRT0-∞ ,27. 09,31.63, 26. 60 h; CL/F,21. 65 ,21. 45 ,20. 62 mL kg-1 . h-l. CONCLUSION Double peak phenomenon is observed in the plasma SQV pro- files. Our study demonstrates that chrysin and naringenin can not significantly affect the SQV oral bioavailability and SQV PK profiles in rats.

关 键 词：白杨黄素 柚皮素 沙奎那韦 药动学 液相色谱串联质谱法 

分 类 号：R969.1[医药卫生—药理学]