三七皂苷中人参皂苷Rg_1与Rb_1口服吸收及其体内药代动力学的研究和比较  

Comparison between the characteristics of absorption and pharmacokinetic behavior of ginsenoside Rg_1 and ginsenoside Rb_1 of panax notoginseng saponins

作　　者：韩旻[1] 傅韶[2,3] 方晓玲[4] 

机构地区：[1]浙江大学药学院 [2]美国匹兹堡大学药学院 [3]复旦大学药学院,上海200032 [4]复旦大学药学院

出　　处：《药学学报》2007年第8期849-853,共5页Acta Pharmaceutica Sinica

摘　　要：分别考察三七总皂苷(PNS)在大鼠灌胃和静脉给药后的人参皂苷Rg1(Rg1)、人参皂苷Rb1(Rb1)的胆汁排泄;采用平衡透析法测定药物的血浆蛋白结合率;并结合药代动力学的实验结果,研究和比较Rg1与Rb1的口服吸收及其体内药代动力学性质。结果表明,静脉给药后10 h,Rg1及Rb1胆汁排泄累积量分别为给药剂量的(61.48±18.30)%和(3.94±1.49)%;灌胃给药后12 h,Rg1及Rb1胆汁排泄累积量分别为给药剂量的(0.91±0.51)%和(0.055±0.02)%。Rg1及Rb1的血浆蛋白结合率分别为6.56%~12.74%和80.11%~89.69%。Rg1的胃、肠和肝的通过率(FS,FI和FH)分别为49.85%,13.05%和50.56%;Rb1分别为25.82%,4.18%和65.77%。因此,肠壁吸收差是Rg1和Rb1生物利用度低的主要原因。Rg1具有较高的胆汁排泄和较低的血浆蛋白结合率,Rb1的胆汁排泄较低,而血浆蛋白结合率较高。Rb1的肠黏膜透过性和体内消除速度都低于Rg1,但前者的平均滞留时间(MRT)和血药浓度曲线下面积(AUC)均大于后者。To compare the characteristics of absorption and pharmacokinetic behavior of ginsenoside Rg_1(Rg_1) with ginsenoside Rb_1(Rb_1) of panax notoginseng saponins(PNS),bile excretion of both Rg_1 and Rb_1 were studied after iv and ig of PNS solution.Plasma protein binding ratios were studied using equilibrium dialysis method,and referred to pharmacokinetic parameters.It shows that(61.48±18.30)% dose of Rg_1 and(3.94±1.49)% dose of Rb_1 were separately excreted into bile 10 hours after iv administration(PNS 50 mg·mL^(-1)),and(0.91±0.51)% dose of Rg_1 and(0.055±0.02)% dose of Rb_1 were excreted into bile 12 hours after ig administration(PNS 1 500 mg·mL^(-1)).Plasma protein binding degrees of Rg_1 and Rb_1 were 6.56%-12.74% and 80.11%-89.69%,respectively.Stomach,intestinal and hepatic throughput efficiency(F_S,F_I and F_H) for Rg_1 were 49.85%, 13.05%,50.56%,respectively,and 25.82%,4.18%,65.77% for Rb_1.Therefore,poor intestinal absorption is a primary reason for the low bioavailability of both Rg_1 and Rb_1.Rg_1 possesses relatively high bile excretion and low plasma protein binding rate,in contrast,Rb_1 possesses low bile excretion and high plasma protein binding rate.Membrane permeability and elimination rate of Rb_1 were lower than that of Rg_1,meanwhile,longer MRT and bigger AUC could be found for Rb_1.

关 键 词：三七总皂苷 人参皂苷Rg1 人参皂苷Rb1 药代动力学 胆汁排泄 血浆蛋白结合率 

分 类 号：R286.0[医药卫生—中药学]