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目的:分析灯盏乙素乙酯(scutellarin ethyl ester,DZY-02)在大鼠小肠各肠段的吸收机制。方法:采用大鼠在体单向肠灌流模型,运用HPLC测定肠灌流液中DZY-02含量,考察3个剂量组DZY-02在大鼠十二指肠、空肠、回肠的吸收情况,分析P-糖蛋白(P-glycoprotein,P-gp)和乳腺癌耐药蛋白(breast cancer resistance protein,BCRP)抑制剂对DZY-02吸收的影响。结果:DZY-02在低、中、高质量浓度下,各小肠段的吸收速率常数和有效渗透系数(Peff)均无显著性差异,Peff均>0.2×10-4cm·s-1。在相同质量浓度下,DZY-02在不同肠段的吸收速率常数均无显著性差异;P-gp和BCRP抑制剂均对DZY-02吸收无影响。结论:DZY-02在大鼠肠道内为高渗透性药物,在小肠内均有吸收,且无特定的吸收窗。在一定质量浓度范围内,DZY-02在大鼠肠道内吸收无高浓度饱和抑制现象,推断DZY-02在大鼠肠道内的吸收机制可能为被动扩散。DZY-02不是P-gp和BCRP蛋白的底物。
Objective: To analyze the absorption mechanism of scutellarin ethyl ester (DZY-02) in rat intestinal segments. METHODS: The rat model of one-way intestinal perfusion was used to determine the content of DZY-02 in intestinal perfusate by HPLC. The absorption of DZY-02 in duodenum, jejunum and ileum of rats in three dose groups was examined. Effects of glycoprotein (P-glycoprotein, P-gp) and breast cancer resistance protein (BCRP) inhibitors on DZY-02 uptake. RESULTS: There was no significant difference in the absorption rate constants and effective efficiencies (Peff) of DZY-02 at low, medium, and high-mass concentrations. The Peff was >0.2×10-4 cm·s-1. At the same mass concentration, there was no significant difference in the absorption rate constants of DZY-02 in different intestinal segments; both P-gp and BCRP inhibitors had no effect on the absorption of DZY-02. Conclusion: DZY-02 is a highly permeable drug in the intestine of rats. It is absorbed in the small intestine and has no specific absorption window. Within a certain range of mass concentration, DZY-02 was not absorbed in rat intestine and there was no high saturation inhibition. It was concluded that the absorption mechanism of DZY-02 in rat intestine may be passive diffusion. DZY-02 is not a substrate for P-gp and BCRP proteins.