在体单向肠灌流模型考察灯盏乙素乙酯的肠吸收特性

Intestinal Absorption Investigation of Scutellarin Ethyl Ester by in situ Single Pass Intestinal Perfusion Model

摘要:

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(P_eff)均无显著性差异, P_eff均>0.2×10^-4 cm·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.

Abstract:

Objective: To investigate absorption mechanism of scutellarin ethyl ester (DZY-02). Method: In situ single pass intestinal perfusion model was established,HPLC was adopted to study absorptions of three dose groups of DZY-02 in different segments,effects of different protein inhibitors on absorption parameters of DZY-02 in different intestinal segments were investigated. Result: Absorption rate constant and effective permeability coefficient (P_eff) were no significantly differences in different segments of rat intestine or concentration of DZY-02, P_eff was more than 0.2×10^-4 cm·s^-1.Protein inhibitors had no obvious effects on intestinal absorption of DZY-02. Conclusion: DZY-02 is a high-permeability candidate drug and can be absorbed in whole intestinal segments,transport mechanism of DZY-02 in vivo is similar to passive diffusion.DZY-02 may be not a substrate of P-glycoprotein and breast cancer resistance protein.