摘要
目的评估桑黄素和乙酰化白藜芦醇对大鼠体内沙奎那韦(P-gp作用底物)药物代谢动力学的影响。方法将SD大鼠分为4组,每组5只,即对照组、实验Ⅰ和Ⅱ组、阳性对照组,分别灌胃给予30 mg·kg-1沙奎那韦;30 mg·kg-1沙奎那韦联用40 mg·kg-1桑黄素;30 mg·kg-1沙奎那韦联用40 mg·kg-1乙酰化白藜芦醇和30 mg·kg-1沙奎那韦联用40 mg·kg-1维拉帕米。采用HPLC-MS/MS方法测定给药后不同时间沙奎那韦的血药浓度,计算药动学参数。结果 4组大鼠体内主要药动学参数分别为:AUC0-t:381.53μg·h·L^(-1),185.53μg·h·L^(-1),360.43μg·h·L^(-1),529.95μg·h·L^(-1);AUC0-∞:409.48μg·h·L^(-1),228.52μg·h·L^(-1),446.67μg·h·L^(-1),552.41μg·h·L^(-1);Cmax:110.80μg·L^(-1),86.44μg·L^(-1),139.84μg·L^(-1),423.60μg·L^(-1);Tmax:0.25 h,0.25 h,0.25 h,0.50 h;T1/2:5.72 h,5.94 h,6.78h,3.78 h;MRT0-∞:10.30 h,9.61 h,12.30 h,4.89 h;CL/F:7.59 m L·kg-1·h-1,13.88 m L·kg-1·h-1,7.28 m L·kg-1·h-1,5.52 m L·kg-1·h-1。结论沙奎那韦的药时曲线存在多峰现象;桑黄素可明显降低沙奎那韦的口服生物利用度并对其药动学参数产生影响,而乙酰化白藜芦醇对沙奎那韦的口服生物利用度和药动学参数没有明显影响。
Aim To assess the impact of morin and acetyl-resveratrol on the oral bioavailability and pharmacokinetics of saquinavir（ SQV）,a substrate of P-glycoprotein（ P-gp）,in rats. Methods Twenty rats were randomized into four groups of equal size,including a control group,two intervention groups and a positive control group,and administered orally 30 mg·kg（-1） SQV with or without 40 mg·kg（-1） morin or acetyl-resveratrol or verapamil（ as positive control）. The plasma concentrations of saquinavir were determined using a high-performance liquid chromatography-tandem mass spectrometry（ HPLC-MS/MS） method,and the PK of SQV was assessed using non-compartmental analysis. Results The PK parameters values of SQV,SQV ＋ morin,SQV ＋ acetyl-resveratrol,SQV ＋ verapamil were as follows： AUC_（0-t）,381. 53 μg·h·L（-1）,185. 53 μg·h ·L（-1）,360. 43 μg·h·L（-1）,529. 95μg · h · L（-1）; AUC_（0-∞）,409. 48 μg · h · L（-1）,228. 52 μg· h · L（-1）,446. 67 μg·h·L（-1）,552. 41μg·h·L（-1）; Cmax,110. 80 μg·L（-1）,86. 44 μg·L（-1）,139. 84 μg·L（-1）,423. 60 μg·L（-1）; Tmax,0. 25 h,0. 25 h,0. 25 h,0. 50 h; T1/2,5. 72 h,5. 94 h,6. 78 h,3. 78 h; MRT_（0-∞）,10. 30 h,9. 61 h,12. 30 h,4. 89 h; CL/F,7. 59 m L·kg-1·h（-1）,13. 88 m L·kg-1·h（-1）,7. 28 m L·kg-1·h（-1）,5. 52 m L·kg-1·h（-1）. Conclusions Multiple peak phenomenon can be observed in the plasma SQV profiles. Morin can significantly reduce the SQV oral bioavailability and affect SQV PK profiles while acetyl-resveratrol cannot significantly affect the SQV oral bioavailability and SQV PK profiles in rats.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2017年第10期1414-1420,共7页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81102877)
