非诺贝特纳米混悬剂大鼠在体肠吸收动力学研究

 目的 考察非诺贝特纳米混悬剂在小肠的吸收动力学特征,并与非诺贝特原料药进行对比。方法 采用大鼠在体肠回流实验,紫外分光光度法测定酚红浓度,HPLC同时测定非诺贝特及非诺贝酸的浓度。结果 非诺贝特纳米混悬剂在整个小肠的吸收速率常数高于其原料药,两者在50~200 μg·mL^-1内的K_a值均基本保持不变,在pH 6.0、6.5、7.4条件下的吸收速率亦无显著性差异,非诺贝特纳米混悬剂在十二指肠、空肠、回肠及结肠的K_a值分别为(0.373±0.002 1)h^-1、(0.329±0.000 8)h^-1、(0.362±0.001 4)h^-1、(0.347±0.007 9)h^-1。结论 非诺贝特纳米混悬剂在整个肠道均有较好吸收,呈一级动力学过程,吸收机制为被动扩散。

Absorption Kinetics of Fenofibrate Nanosuspension in Rat Intestine in Situ

OBJECTIVE To investigate the absorption kinetics of fenofibrate nanosuspension in rat intestine．METHODS The intestine of rats was cannulated for in situ recirculation．UV spectrophotometry was used to determine the concentrations of phenol red while HPLC was used to determine the concentrations of　fenofibrate and fenofibric acid．RESULTS The fenofibrate nanosuspension exhibited substantial absorption enhancement in entire intestine compared to the crude drug solution．The difference in drug absorption at concentrations from 50 to 200 μg·mL^-1 between fenofibrate nanosuspension and crude drug solution was not significant. Different pH values of K-R buffer had no effect on the intestinal permeability (P_app)and absorption rate constant (K_a)for the two dosage forms. The absorption rate constants (h^-1)of fenofibrate nanosuspension at duodenum,jejunum,ileum and colon were (0.373±0.002 1),(0.329±0.000 8),(0.362±0.001 4), and (0.347±0.007 9), respectively．CONCLUSION Fenofibrate nanosuspension can be well absorbed in the whole intestinal segments．The absorption of　fenofibrate nanosuspension in rat intestine is a first order process with passive diffusion mechanism.