不同相对分子质量灯盏乙素-PEG酯大鼠在体小肠吸收动力学的研究

 目的考察灯盏乙素-聚乙二醇(PEG)酯在大鼠各肠段吸收动力学特征及不同的药物浓度和相对分子质量对吸收的影响,以探讨PEG修饰及相对分子质量的变化对小分子药物口服吸收的影响规律。方法应用大鼠在体肠吸收实验法。结果灯盏乙素-PEG400酯在十二指肠、空肠、回肠的吸收速率常数分别为0.132 6,0.079 9,0.081 9 h^-1;不同浓度的灯盏乙素(30,100,200 mg·L^-1)在小肠的吸收速率常数分别为0.029 2,0.033 8,0.030 6 h^-1;不同浓度的灯盏乙素-PEG400酯(40,130,260 mg·L^-1)在小肠的吸收速率常数分别为0.157 7,0.162 4,0.170 8 h^-1;灯盏乙素,灯盏乙素-PEG200,400,1000酯在小肠的吸收速率常数分别为0.033 8,0.154 7,0.162 4,0.068 0 h^-1。结论灯盏乙素经PEG化后,口服吸收明显增加,但随着PEG片断相对分子质量的增大,其PEG化物的吸收相应减少;灯盏乙素-PEG酯在十二指肠吸收较好;药物浓度对吸收速率常数无影响,药物在肠道的吸收呈一级动力学过程,吸收机制为被动扩散。

Absorption Kinetics of Scutellarin-PEG Conjugates in Rat Intestine

OBJECTIVE To investigate the absorption kinetics of scutellarin-PEG conjugates at different intestine segments of rats and the influence of different concentration and molecular weight of the drugs on the intestinal absorption after PEGylation.METHODS The intestine in rats was cannulated for in situ recirulation.RESULTS The absorption rate constant(K_a) at duodenum,jejunum and ileum were 0.132 6,0.079 9,0.081 9 h^-1,respectively.The K_a of scutellarin at the concentrations of 30,100 and 200 mg·L^-1 in intestine were 0.029 2,0.033 8,0.030 6 h^-1 while the K_a of scutellarin-PEG400 conjugates at the concentrations of 40,130 and 260 mg·L^-1 were 0.157 7,0.162 4 and 0.170 8 h^-1,respectively.The K_a of scutellarin and its PEG200,400,1000 conjugates were 0.033 8,0.154 7,0.162 4 and 0.068 0 h^-1,respectively.CONCLUSION The PEGylation enhances the absorption of scutellarin in rat intestine.However,among the PEG conjugates,with the increased PEG molecular weight,the absorption of conjugates decreases accordingly.The conjugates are well absorbed at the duodenum in rats.The concentration has no effect on the absorption kinetics.The absorption of scutellarin and its conjugates are a first-order process with the passive diffusion mechanism.