八珍汤中芍药苷、阿魏酸肠吸收影响因素研究

Influence factors of Paeoniflorin and Ferulic acid absorption in intestines of rats

考察药物质量浓度、肠段、pH值及P-gp对八珍汤中芍药苷、阿魏酸肠吸收的影响规律.采用大鼠在体循环灌流法,应用HPLC测定肠吸收循环液中芍药苷、阿魏酸的质量浓度,UV法测定肠吸收循环液中即时酚红质量浓度.芍药苷、阿魏酸分别在0.08-0.64 mg/mL和0.008-0.064 mg/mL范围内,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（Ka）、累积吸收百分率（A）及t1/2无显著性差异;pH值在7.8-5.8范围内对芍药苷无显著影响,而阿魏酸的吸收量、Ka、A,随着pH值的减小而增加（P〈0.05）;在消化系统中,芍药苷各参数无显著性差异,而阿魏酸在胃中的吸收量、Ka、A显著增大（P〈0.05）;此外,P-gp抑制剂维拉帕米对芍药苷、阿魏酸的吸收有明显促进作用（P〈0.05）,P-gp诱导剂利福平对芍药苷、阿魏酸的吸收有明显的抑制作用（P〈0.05）.芍药苷、阿魏酸在肠道的吸收均呈一级动力学过程,推断为被动扩散;芍药苷无特定的吸收部位,阿魏酸在胃中显显著被吸收;芍药苷、阿魏酸为P-gp底物,可通过与P-gp抑制剂合用提高其生物利用度,而与P-gp诱导剂合用则降低其生物利用度.

To investigate the absorption of Paeoniflorin and Ferulic acid at different intestine segments of rats and the influence of the drug solution concentration,pH value,P-gp inhibitor.The intestine cannulation is performed for insitu recirculation.Paeoniflorin,Ferulic acid and phenol red concentration in the flux are separately measured by the reversed phase HPLC and UV.When the concentration is raised from 0.08 to 0.64 mg/mL and 0.008～0.064 mg/mL,the uptake of Paeoniflorin and Ferulic acid is separately linearly increased（r0.999）,and no changes of Ka,absorption fraction and t1/2 are found.The pH value of flux has no effect on Paeoniflorin absorption,while the absorption of Ferulic acid is increased when pH value of the drug solution is lowered（P0.05）.In the digestive system,the parameters of paeoniflorin is no significant difference,while ferulic acid in the stomach＇s absorption,Ka,A increased significantly（P 0.05）.Further more,P-gp inhibitor verapamil and P-gp inducer rifampicin have obvious effect on the intestinal absorption of Paeoniflorin and Ferulic acid（P0.05）.The absorption of Paeoniflorin and Ferulic acid in intestine of rat are first-order kinetics,but Ferulic acid,the absorption mechanism is infered the passive diffusion.Paeoniflorin has no specific absorption locus in intestine of rat.Paeoniflorin and Ferulic acid are P-gp substrate,and could increase its fraction of bioavailability by corporation with P-gp inhibitor,but P-gp inducer can decrease its fraction of bioavailability.