白桦脂酸在大鼠体肠吸收动力学的研究

目的:建立同时测定肠循环液中白桦脂酸和酚红浓度的HPLC-DAD法,并探讨白桦脂酸在大鼠各肠段的吸收动力学特征及不同药物浓度对吸收的影响。方法:采用大鼠在体肠吸收实验模型,并考察吸收部位、药物浓度和pH对药物吸收的影响。结果:在75～125 mg.L-1白桦脂酸的吸收速率与质量浓度呈线性关系,Ka基本保持不变;各肠段的吸收速率无显著性差异,十二指肠、空肠、回肠和结肠的Ka分别为(0.151±0.004 9),(0.159±0.005 6),(0.156±0.008 3),(0.149±0.004 1)h-1。结论:白桦脂酸在小肠中吸收良好,没有特定吸收部位;不同浓度对白桦脂酸在大鼠全肠道的吸收无显著影响,其在肠道的吸收呈一级吸收动力学特征,吸收机制为被动扩散。白桦脂酸是难溶性药物,可以通过增加药物的溶出度,进而提高药物的生物利用度。

Study on absorption kinetics of betulic acid in rat's intestines

Objective: To establish a HPLC-DAD method for determining concentrations of betulic acid and phenol red in intestinal circulation liquid, and probe into the absorption kinetic characteristics of betulic acid at different intestine segments in rats and the effect of different drug concentrations on absorption. Method: The rat intestinal absorption model was established to detect the impact of absorption site, drug concentration and pH value on drug absorption. Result: Within the range from 75-125 mg·L^-1, the absorption rate and the quality concentration of betulic acid had a linear relation, with Ka value keeping unchanged. The absorption rate for each intestinal segment showed no remarkable difference, with Ka values in duodenum, jejunum, ileum and colon being (0.151±0.004 9), (0.159±0.005 6), (0.156±0.008 3), (0.149±0.004 1) h^-1, respectively. Conclusion: Betulic acid is proved to be well absorbed in intestines marked by no specific absorption site in the intestine. The absorption mechanism of the drug conforms to passive transport mechanism and first-order kinetics. The bioavailability of betulic acid preparation can be increased by enhancing the dissolution rate and the solubility.