川芎嗪大鼠在体肠吸收动力学

The intestinal absorption kinetics of ligustrazine in rats

目的:探讨川芎嗪在大鼠各肠段的吸收动力学特征.方法:采用大鼠在体小肠回流装置,以UV法和HPLC法分别测定酚红和川芎嗪的含量.结果:川芎嗪在小肠的吸收速率常数(Ka)于不同药物浓度2.5,5,10,25 mg·L-1时分别为0.360 8,0.388 1,0.444 6,0.385 9 h-1;不同pH值7.8,6.8,5.4时分别为0.466 4,0.413 9,0.270 5 h-1;在十二指肠,空肠,回肠和结肠时分别为0.291 3,0.220 9,0.172 8,0.133 3 h-1.结论:药物浓度对Ka无影响;在pH 7.8～5.4范围内,随药液pH值的增大,药物的Ka显著增加;药物在十二指肠、空肠和回肠的吸收较好,在结肠的吸收较差;川芎嗪在肠道的吸收呈一级动力学过程,吸收机制为被动扩散.

OBJECTIVE To investigate the absorption kinetics of ligustrazine at different intestine segments in rats. METHODS The intestine in rats was eannulated for in situ reeireulation. UV and HPLC were used to determine the concentrations of phenol red and ligustrazine, respectively. RESULTS The absorption rate constant （Ka） at the concentration of 2. 5,5,10 and 25 mg. L^-1 from intestine were 0. 360 8,0. 388 1,0. 444 6 and 0. 385 9 h^-1 , respectively. K~ at pH of 7. 8,6. 8,5. 4 from intestine were 0. 466 4, 0. 413 9 and 0. 270 5 h^-1 ,respeetively;Ka at duodenum,jejunum, ileum and colon were 0. 291 3,0. 220 9,0, 172 8 and 0. 133 3 h^-1, respectively. CONCLUSION Concentration had no effect on the absorption kinetics. In the range of pH 5.4-7. 8, the absorption of the drug increase with the increasing of pH Value of the drug solution. Ligustrazine can be better absorbed at duodenum,jejunum and ileum than at colon. The absorption of ligustrazine is a first-order process with the passive diffusion mechanism.