辛伐他汀大鼠肠吸收动力学研究

目的:研究辛伐他汀在大鼠各肠段的吸收动力学特征。方法:采用大鼠在体肠段回流实验,主要从吸收部位、药物浓度、pH值方面对辛伐他汀的肠段吸收特性进行研究。结果:辛伐他汀在大鼠肠道内无特定吸收部位,各肠段吸收速率常数按十二指肠、结肠、空肠、回肠顺序依次下降,分别为0.03365、0.03190、0.02942、0.02563h-1。辛伐他汀在1.0～20.0μg·mL-1浓度范围内药物吸收量呈线性关系;在pH5.0～7.4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,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次缓释给药系统。

Absorption Kinetics of Simvastatin in Rats

OBJECTIVE： To study the absorption characteristics of simvastatin in different intestinal segments. METHODS： The intestinal perfusion experiment was performed on rats in vivo to observe the effects of absorption sites, drug concentration, and pH value on the intestinal absorption characteristics of simvastatin. RESULTS： Simvastatin showed no specific absorption site in rat＇s intestine. The absorption rate constants deceased from duodenum, colon and jejunum to ileum in order （0.033 65〉 0.031 90〉 0.029 42〉 0.025 63 h 1） . A linear relation between absorption and concentration was noted for simvastatin at a concentration of 1.0-20.0μg·mL^-1 and within a pH value of 5.0-7.4, the absorption of simvastatin was not affected. CONCLUSION： Simvastatin showed absorption behavior in the whole section of intestine. The absorption of the drug conforms to the passive transport mechanism and first order kinetics. The results indicate that simvastatin can be formulated and prepared into sustained release drug delivery system.