人参中人参皂苷Rg1，Rb1在体肠吸收影响因素的研究

目的:考察药物浓度、肠段、pH及P-gp对人参中人参皂苷Rg_1,Rb_1肠吸收的影响规律.方法:采用大鼠在体循环灌流法,应用HPLC测定肠吸收循环液中人参皂苷Rg1,Rb1的浓度,UV法测定肠吸收循环液中即时酚红浓度.结果:人参皂苷Rg1,Rb1分别在0.075～0.75 g·L~(-1)和0.03～0.3 g·L~(-1),各浓度的吸收量与药物浓度呈良好线性关系(r>0.999),且吸收速率常数(K)、累积吸收百分率(A%)及t_(1/2)无显著性差异;pH对人参皂苷Rg_1,Rb_1吸收均无显著影响;各个肠段人参皂苷Rg.的吸收量,K_a,A%及t_1/2值无显著性差异,而人参皂苷Rb_1.在空肠循环的各参数显著高于十二指肠和回肠(P<0.05);此外,P-gp抑制剂维拉帕米对人参皂苷Rb_1的吸收有明显促进作用(P<0.05),而对人参皂苷Rg_1无此作用.结论:人参皂苷Rg_1,Rb_1在肠道的吸收均呈一级动力学过程,推断为被动扩散;人参皂苷Rg_1无特定的吸收部位,而人参皂苷Rb_1在空肠段具吸收部位选择性;人参皂苷Rb_1为P-gp底物,可通过与P-gp抑制剂合用提高其生物利用度.

Studies on influence factors of gnsenoside Rg1 and Rb1 absorption in intestines of rats

Objective: To investigate the absorption of gnsenoside Rg₁and Rb₁ in Radix Gngseng at different intestine segments of rats and the influence of the drug solution concentration, pH, P-gp inhibitor. Method: The intestine cannulation was performed for in situ recirculation. Gnsenoside Rg₁, Rb₁ and phenol red concentration in the flux were separately measured by the reversed phase HPLC and UV. Results: When the concentration was raised from 0.075-0.75 g·L^-1 and 0.03-0.3 g·L^-1, the uptake of ginsenoside Rg₁ and Rb₁ was separately linearly increased (r>0.999), and no changes of K_a, absorption fraction and t_1/2 are found. The pH of flux has no effect on drug absorption. Ginsenoside Rg₁ can be absorbed in the whole intestine and no changes of K_a, absorption fraction and t_1/2 are found and all the parameters of ginsenoside Rb₁ at jejunum are higher than that at ileum and duodenum (P<0.05). Further more, P-gp inhibitor verapamil has obvious effect on the intestinal absorption of ginsenoside Rb₁(P<0.05), while it has no effect on ginsenoside Rg₁. Conclusion: The absorption of ginsenoside Rg₁ and Rb₁ in intestine of rat are first-order kinetics, the absorption mechanism is infered the passive diffusion. Ginsenoside Rg₁ has no specific absorption locus in intestine of rat and ginsenoside Rb₁ has specific absorption locus of jejunum. Meanwhile, ginsenoside Rb₁ is the P-gp substrate, and could increase its fraction of bioavailability by corporation with P-gp inhibitor.