吗替麦考酚酯大鼠在体肠吸收动力学研究

Studies on the intestinal absorption kinetics of mycophenolatemofetil in rats

目的:研究吗替麦考酚酯(MMF)、麦考酚酸(MPA)在大鼠肠道的吸收特性。方法:采用大鼠在体肠吸收实验模型,考察不同药物浓度、不同肠段、不同pH对MMF、MPA肠吸收特性的影响。结果:MMF在十二指肠、空肠、回肠、结肠的吸收速率常数分别为0.0176,0.0219,0.0311,0.0333 h-1,统计结果显示,不同肠段间吸收有明显差异(P<0.05);在pH 5.4～7.4范围内,药物吸收不受pH影响;65,135,200,300μg·mL-1不同浓度MMF的吸收速率常数分别为0.0964,0.1325,0.1655,0.1222h-1,而不同浓度MPA的吸收速率常数基本不变(P>0.05)。结论:MMF在整个肠段均有吸收,剂型设计时可考虑缓控释制剂。

Objective：To study the absorptivecharacters of MMF and MPAin rats＇ intestines.Methods：An in situ intestinal perfusion model was employed to investigate systemically the absorptive characterof MMF and MPA.The effects of pH value,absorption site and drug concentration on drug absorption were studied.Results：The absorption rate constant（Ka）of MMF were 0.0176,0.0219,0.0311,0.0333 h-1 at duodenum,jejunum,ileum,and colon respectively（P0.05）.Within the range of 5.4-7.4,pH value had no influence on absorption of drug.The Ka of MMF were 0.0964,0.1325,0.1655,0.1222 h-1 at the concentration of 65,135,200,300 μg·mL-1 while the Ka of MPA were kept unvaried basically.Conclusion：MMFwere absorbed at all the segment of intestine in rats.It was suggested that MMF could be designed as sustained-release dosage form.