泛昔洛韦大鼠在体肠吸收动力学研究

Studies on the Intestinal Absorption Kinetics of Famciclovir in Rats

目的研究泛昔洛韦在大鼠各肠段中的吸收动力学特征。方法采用大鼠在体小肠回流试验装置,利用紫外分光光度法、一阶导数光谱法和HPLC法分别测定循环液中酚红、泛昔洛韦及血浆中喷昔洛韦的含量。结果泛昔洛韦在药物浓度为25、50、100μg·ml-1时,全小肠段的吸收速率常数分别为0.304、0.313、0.288h-1;在pH值为5.4、6.8、7.8时,全小肠段的吸收速率常数分别为0.246、0.279、0.251h-1;在十二指肠、空肠、回肠、结肠的吸收速率常数分别为0.147、0.191、0.194、0.047h-1。结论不同的药物浓度、pH值对药物在大鼠全肠道的吸收无显著影响,药物的吸收呈一级动力学过程,吸收机制为被动扩散。

Aim To investigate the absorption kinetics of famciclovir at different intestiine segments in rats. Methods The intestine in rats was cannulated for in situ recirculatrion. UV and the first derivative spectrophotometric method were used to determine the concentrations of phenolsulfonphthalein and famciclovir in the circulating solution respectively,and HPLC was used to determine the concentration of penciclovir in the plasma. Results The absorption constants （Ka） from intestine at famciclovir concentration of 25,50,100 μg·ml^- 1 were 0. 300,0.313 and 0.288 h^ -1 respectively ; Ka at pH of 5.4,6.8 and 7.8 were 0. 246 ,0. 279 and 0.251 h ^-1 respectively; Ka at duodenum, injunum, ileum,mid colon were 0.147,0. 191,0. 194 and 0.007h^-1 respectively. Conclusion The concentrations of famciclovir and the pH of drug solution had no distinct effect on the absorption kinetics. The absorption of famciclovir was a first order process with passive diffusion mechanism. Famciclovir was well absorbed at all segments of intestine in rats.