辛伐他汀在大鼠中在体肠吸收动力学研究

目的：研究辛伐他汀在大鼠各肠段的吸收动力学。方法：采用大鼠在体肠段灌流实验，以HPLC法测定辛伐他汀和酚红在肠回流液中的浓度，观察吸收部位、药物浓度、pH值3个因素对辛伐他汀肠吸收特性的影响。结果：辛伐他汀在大鼠肠道内无特定吸收部位，在十二指肠、结肠、空肠和回肠的吸收速率常数分别为0．0397、0．0342、0．0316、0．0282／h。在pH5．0～7．4范围内药物吸收不受pH值影响。结论：辛伐他汀在大鼠全肠段均有吸收，符合一级动力学特征，吸收机制为被动扩散，适于制备日服1次的缓释给药系统。

Intestinal absorption kinetics of simvastatin in rats

Objective： To explore the absorption kinetics of simvastatin at different segments of intestine in rats. Methods. Intestine of rats was cannulated for in situ perfusion. HPLC method was used to determine the concentrations of simvastatin and phenolsulfonphthalein in circulating solution. The influence of absorption site, concentration of drug and pH value on absorption characteristics of simvastatin was studied. Results： Simvastatin had no specific absorption site in intestine of rats. The absorption rate constants were 0. 039 7, 0. 034 2, 0. 031 6,0. 028 2 /h at duodenum, colon, jejunum and ileum, respectively. Within the range of 5.0-7.4, pH value had no influence on absorption of the drug. Conclusion： Simvastatin can be absorbed in the whole intestine. The absorption process conforms to passive transport mechanism and first-order kinetics. The results indicate that simvastatin can be formulated and prepared as sustained-release preparation which is given once daily.