【摘要】 目的应用完整大鼠间断连续取血模型研究黄芪甲苷包合体的药动学和绝对生物利用度。方法 30只雄性SD大鼠分为5组,每组6只,分别给予黄芪甲苷水剂(20 mg.kg-1)、黄芪甲苷包合体(5.0,10.0和20.0 mg.kg-1)灌胃,以及黄芪甲苷水剂(2.0 mg.kg-1)注射。每只大鼠间断连续取血,所有的血样以地高辛为内标,用液质联用仪(HPLC-MS)测定。结果黄芪甲苷和地高辛m/z比分别为807.5和803.5。黄芪甲苷包合体(5.0,10.0和20.0 mg.kg-1)的t1/2β分别为(10.73±3.34),(11.47±3.28)和(12.88±2.03)h,CL分别为(0.88±0.09),(0.90±0.63)和(0.85±0.04)L.h-1,Vc分别为(6.73±1.78),(5.66±2.23)和(5.72±2.41)L.kg-1,AUC0-t分别为(1 099.09±84.32),(2 174.68±232.98)和(4 800.24±214.86)ng.h.mL-1。黄芪甲苷包合体的绝对生物利用度为10.2%~11.2%,而黄芪甲苷水剂的绝对生物利用度只有3.2%。结论包合体是提高黄芪甲苷绝对生物利用度的有效剂型,值得深入研究。更多还原

【Abstract】 OBJECTIVE To investigate the pharmacokinetics and absolute bioavailability of astragaloside Ⅳ(AGS-Ⅳ) inclusion compound using an intermittent blood sampling technique in intact rats.METHODS Thirty rats,6 rats for each group,were given AGS-Ⅳ aqueous solution(20.0 mg·kg-1) or AGS-Ⅳ inclusion compound(5.0,10.0 and 20.0 mg·kg-1,respectively) by oral administration,or AGS-Ⅳ aqueous solution(2.0 mg·kg-1) by intravenous injection.After medication,blood samples were drawn intermittently in each intact rat.The concentrations of AGS-Ⅳ were measured by liquid chromatography-electrospray ionization-mass spectrometry(LC-ESI-MS) with digoxin as the internal standard(IS).RESULTS The samples were monitored with selected ion recording(SIR) mode of positive ions and target ions at m/z 807.5 for AGS-Ⅳ and m/z 803.5 for IS.The pharmacokinetic parameters of AGS-Ⅳ inclusion compound(5.0,10.0 and 20.0 mg·kg-1) were as follows: t1/2β(10.73±3.34),(11.47±3.28) and(12.88±2.03) h,CL(0.88±0.09),(0.90±0.63) and(0.85±0.04) L·h-1,Vc(6.73±1.78),(5.66±2.23) and(5.72±2.41) L·kg-1,and AUC0-t(1 099.09±84.32),(2 174.68±232.98) and(4 800.24±214.86) ng·h·mL-1,respectively.The absolute bioavailability was 10.2%-11.2% for the inclusion compound,and 3.2% for the aqueous solution.CONCLUSION Inclusion compound is a effective dosage form to enhance the bioavailability of AGS-IV,which is worth further investigation.更多还原