西尼地平大鼠在体肠吸收药物动力学研究

Intestinal absorption pharmacokinetics of cilnidipine in rats

目的研究西尼地平在大鼠各肠段的药物动力学吸收特点。方法采用大鼠在体肠灌流实验装置,利用紫外-可见分光光度法和HPLC法分别测定酚红和西尼地平的含量。结果西尼地平在十二指肠、空肠、回肠、结肠的吸收速率分别为(2.05±0.013)、(1.95±0.010)、(1.96±0.005)、(1.82±0.005)h-1;药物质量浓度为5、10、15 mg·L-1时,在肠的吸收速率常数分别为(2.25±0.006 9)、(2.24±0.005 3)、(2.24±0.005 7)h-1;当pH值为6.4、7.2、7.9时,肠的吸收速率常数分别为(2.23±0.012 3)、(2.24±0.005 3)、(2.21±0.213 1)h-1。结论不同质量浓度的西尼地平在大鼠全肠道的吸收无显著差异,吸收机制为被动扩散;西尼地平在各肠段吸收较好。

Objective To investigate the absorption pharmacokinetics of cilnidipine at different intestine segments in rats.Methods The intestine in rats was cannulated for in situ perfusation.UV and HPLC were used to determine the concentrations of phenol red and cilnidipine,respectively.Results The absorption rate constants(ka) at duodenum,jejunum,ileum,and colon were(2.05±0.013)h-1,(1.95±0.010) h-1,(1.96±0.005) h-1,(1.82±0.005) h-1respectively.The ka from intestine at cilnidipine concentration of 5 mg·L-1,10 mg·L-1,15mg·L-1were(2.25±0.006 9) h-1,(2.24±0.005 3) h-1,(2.24±0.005 7) h-1; ka at pH of 6.4,7.2,7.9 were(2.23±0.0123) h-1,(2.24±0.0053) h-1,(2.21±0.2131) h-1.Conclusion The effects of the different concentrations on the cilnidipine absorption kinetics were not significant.The absorption of cilnidipine from intestine was a process with passive diffusion michanism.Cilnidipine was well absorbed at all segments of intestine in rats.