洛伐他汀对七叶皂苷在大鼠体内药代动力学的影响  

Effects of lovastatin on the pharmacokinetics of escin in rats

作　　者：吴秀君[1] 马然[1] 于艳[1] 刘美[2] WU Xiu-jun;MA Ran;YU Yan;LIU Mei(Phase Ⅰ Clinical Trial Ward,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning Province,China;College of Pharmacy,China Medical University,Shenyang 110122,Liaoning Province,China)

机构地区：[1]辽宁中医药大学附属医院Ⅰ期临床试验病房,辽宁沈阳110032 [2]中国医科大学药学院,辽宁沈阳110122

出　　处：《中国临床药理学杂志》2020年第20期3350-3354,共5页The Chinese Journal of Clinical Pharmacology

基　　金：辽宁省自然科学基金资助计划(201602498)。

摘　　要：目的研究洛伐他汀对七叶皂苷在大鼠体内药代动力学的影响。方法将SD大鼠随机分为2组:实验组和对照组,每组6只。实验组灌胃洛伐他汀20 mg·kg^-1,对照组灌胃等量溶媒后,2组均尾静脉注射注射用精氨酸七叶皂苷钠1.67 mg·kg^-1(分别相当于0.5 mg·kg^-1七叶皂苷A、0.3 mg·kg-1七叶皂苷B、0.5 mg·kg^-1七叶皂苷C和0.3 mg·kg^-1七叶皂苷D),并于注射前和注射后0.083,0.25,0.5,1,1.5,2,3,4,6,8,12,24,36和48 h经大鼠眼眶静脉采血,用液相色谱-质谱联用(LC-MS/MS)法测定七叶皂苷A、B、C、D的血药浓度。流动相为0.05%甲酸10 mmol·L^-1醋酸铵和甲醇:乙腈=1:1(v/v),梯度洗脱;内标为罗红霉素。用Topfit 2.0软件计算药代动力学参数。结果实验组和对照组主要药代动力学参数如下:实验组七叶皂苷A、B、C、D的平均AUC0-t分别为(11.89±2.81),(3.83±0.71),(28.33±8.00),(6.45±3.42)μg·h·mL^-1,对照组分别为(8.73±2.54),(2.46±0.78),(22.54±18.55),(6.08±2.16)μg·h·mL^-1;实验组平均AUC0-∞分别为(12.02±2.86),(3.86±0.78),(29.69±9.12),(6.50±3.63)μg·h·mL^-1,对照组分别为(8.93±2.70),(2.51±0.81),(23.95±20.50),(6.21±2.24)μg·h·mL^-1;实验组平均CL分别为(3.05±1.36),(1.79±0.41),(0.32±0.14),(1.58±0.67)mL·min^-1,对照组分别为(2.29±3.10),(2.92±1.59),(0.61±0.43),(0.93±0.21)mL·min^-1;实验组平均t1/2分别为(8.76±0.15),(4.86±1.91),(8.23±2.43),(4.21±2.46)h,对照组分别为(8.53±2.78),(3.21±2.47),(8.19±4.92),(6.09±2.21)h。实验组与对照组比较,七叶皂苷B的AUC0-t和AUC0-∞均增加,差异均有统计学意义(均P<0.05)。结论洛伐他汀可影响七叶皂苷的大鼠体内药代动力学行为,增加其体内暴露水平。Objective To study the effect of lovastatin on the pharmacokinetic of escin in rats.Methods SD rats were randomly divided into test group and control group with 6 rats in each group.The rats were intravenously given arginine sodium aescinate 1.67 mg·kg^-1(equals to 0.5 mg·kg^-1 escin A,0.3 mg·kg^-1 escin B,0.5 mg·kg^-1 escin C and 0.3 mg·kg^-1 escin D,respectively)via tail vein after oral administration of vehicle for control group or lovastatin 20 mg·kg^-1 for test group.Blood samples were collected before and 0.083,0.25,0.5,1,1.5,2,3,4,6,8,12,24,36 and 48 h after arginine sodium aescinate adminstration.The plasma concentration of escin A,B,C and D were determined by an LC-MS/MS method.Mobile phase consisted of 0.05% formic acid 10 mmol·L^-1 ammonium acetate and methanol:acetonitrile=1:1(v/v)with gradient elution.Roxithromycin was selected as internal standard.Pharmacokinetic parameters were calculated by Topfit 2.0 software.Results The pharmacokinetic parameters of escin A,B,C and D in test group and control group were as follows:the mean AUC0-t of escin A,B,C and D was(11.89±2.81),(3.83±0.71),(28.33±8.00),(6.45±3.42)μg·h·mL^-1 and(8.73±2.54),(2.46±0.78),(22.54±18.55),(6.08±2.16)μg·h·mL^-1,respectively;the mean AUC0-∞ of escin A,B,C and D was(12.02±2.86),(3.86±0.78),(29.69±9.12),(6.50±3.63)μg·h·mL^-1 and(8.93±2.70),(2.51±0.81),(23.95±20.50),(6.21±2.24)μg·h·mL^-1,respectively;the mean CL of escin A,B,C and D was(3.05±1.36),(1.79±0.41),(0.32±0.14),(1.58±0.67)mL·min^-1 and(2.29±3.10),(2.92±1.59),(0.61±0.43),(0.93±0.21)mL·min^-1,respectively;the mean t1/2 of escin A,B,C and D was(8.76±0.15),(4.86±1.91),(8.23±2.43),(4.21±2.46)h and(8.53±2.78),(3.21±2.47),(8.19±4.92),(6.09±2.21)h,respectively.Compared with control group,both the AUC0-t and AUC0-∞ of escin B were increased,with statistically significant differences(P<0.05).Conclusion Lovastatin may affect the pharmacokinetic of escin in rats and increase its exposure in vivo.

关 键 词：七叶皂苷 洛伐他汀 LC-MS/MS 药代动力学 

分 类 号：R28[医药卫生—中药学]