不同剂量人参茎叶总皂苷对阿司匹林大鼠体内药动学的影响

Effects of different doses of total ginsenoside of ginseng stems and leaves on the pharmacokinetics of aspirin in rats

关键词:  人参茎叶总皂苷  阿司匹林  水杨酸  药代动力学

Key words:  ginsenoside of stems and leaves  aspirin  salicylic acid  pharmacokinetics

摘要:

[目的]研究不同浓度人参茎叶总皂苷对阿司匹林在大鼠体内代谢物水杨酸药动学的影响。[方法]30只SD大鼠随机均分为阿司匹林单用组，低、中、高剂量人参茎叶总皂苷与阿司匹林单次联用组，中剂量阿司匹林与人参茎叶总皂苷长期联用组，通过灌胃给药后，分别于灌胃后0.083、0.25、0.5、1、2、4、6、8、10 h经眼眶取血0.5 mL，采用HPLC-UV分析检测大鼠血浆中阿司匹林代谢物——水杨酸的血药浓度，并通过DAS3.0软件的非房室模型计算水杨酸的药代动力学参数，比较各组之间的参数。[结果]与阿司匹林单用组相比，低剂量（20 mg/kg）和中剂量（40 mg/kg）的人参茎叶总皂苷对阿司匹林在大鼠体内药动学无显著影响，但高剂量（80 mg/kg）的人参茎叶总皂苷与阿司匹林联用后，水杨酸在体内的C_max以及AUC_（0-t）显著增加，V与CL显著降低（P<0.05）；长期服用中剂量人参茎叶总皂苷，亦可显著增加水杨酸在体内的C_max以及AUC_（0-t）。[结论]在一定剂量范围（40~80 mg/kg）内，人参茎叶总皂苷可以增加阿司匹林在体内的血药浓度，增加其生物利用度，且存在一定的剂量相关性和时间相关性。

Abstract:

[Objective] To study the effects of different concentrations of total ginsenoside of ginseng stems and leaves (TGSL) on the pharmacokinetics of aspirin in the metabolite salicylic acid in rats.[Methods] The 30 SD rats were randomly divided into the aspirin single-use group,the low,medium and high doses of TGSL combined group,and the long-term TGSL group. The 0.5 mL of blood samples was taken from the eye-lids at 0.083,0.25,0.5,1,2,4,6,8 and 10 h after intragastric administration. The plasma concentration of aspirin metabolite-salicylic acid in rat plasma was measured by HPLC-UV,and the pharmacokinetic parameters of salicylic acid were calculated by the non-compartmental model of DAS 3.0 software.[Results] Compared with aspirin group,TGSL at low dose (20 mg/kg) and medium dose (40 mg/kg) had no significant effect on the pharmacokinetics of aspirin in rats,but the combined use of high dose (80 mg/kg) of TGSL with aspirin significantly increased C_max and AUC_(0-t) of salicylic acid in vivo,and significantly decreased V and CL (P<0.05). The C_max and AUC_(0-t) of salicylic acid in vivo were also significantly increased under the long-term use of TGSL.[Conclusion] Within a certain dose range (40~80 mg/kg),TGSL can improve the plasma concentration of aspirin in vivo and increase its bioavailability,and there is a dose-dependent and time-dependent relationship.