Physiological and Anatomical Factors Controlling Intestinal Drug Absorption Mechanism

作为控制药物吸收机制的两个因素，分析了药物的渗透途径和血流依赖性。巯基乙酸钠（C10）可促进吸收不良的头孢美唑在大鼠结肠和空肠的吸收。其在结肠中的增强作用大于空肠。对于结肠细胞间（细胞旁）通路，C10增加了等效孔半径；从不同分子量的水溶性非电解质的膜透性与其自由扩散系数的关系可知，C10增加了大孔和小孔的透性。阻抗分析表明，C10降低了结阻，增加了膜电容，支持结漏增加和细胞间隙增大。空肠细胞间通路未见C10效应。电压箝位法也观察到类似的位点依赖性增强。荧光偏振技术表明，C10与膜蛋白或脂质相互作用引起的膜扰动增强了膜的通透性。C10增加的跨细胞通透性在空肠中比在结肠中更明显。因此，C10对空肠和结肠对头孢美唑吸收的影响差异被认为主要是由于其对细胞间途径的影响不同。对于血流依赖性药物吸收，采用全氟化学乳剂作为血管灌注液，同时进行管腔和血管灌注试验。发现这种乳剂保留了药物运输的正常屏障功能。血流阻力对安替比林吸收总阻力的贡献大于对水杨酸吸收总阻力的贡献。从白蛋白对毛细血管壁的直接作用出发，研究了血管灌注液中白蛋白对药物吸收的影响。少

As two factors controlling drug absorption mechanism, permeation routes and blood flow dependence were analyzed. The colonic and jejunal absorption of poorly-absorbed cefmetazole were enhanced by sodium caprate (C10) in the rat. Its enhancing effects was greater in the colon than in the jejunum.For the intercellular (paracellular) pathways in the colon, C10 increased the equivalent pore radii ; C10 increased permeability through large and small pores which was obtained from the relationship between the membrane permeability of water-soluble non-electrolytes with various molecular weights and their free diffusion coefficients. Impedance analysis showed that C10 decreased the junctional resistance and increased the membrane capacitance, supporting the increase in junctional leakiness and the enlargement of intercellular space. For the intercellular pathways in the jejunum, no C10 effect was found. The similar site-dependent enhancement was observed also by the voltage clamp method.For th … More e transcellular pathway, fluorescence polarization technique showed that membrane perturbation through the interaction between C10 and membrane protein or lipids enhances the membrane permeability. Transcellular permeability increased by C10 was greater in the jejunum than in the colon. Consequently, the difference between the effects of C10 on the jejunal and colonic absorption of cefmetazole was considered to be due mainly to the difference in its effects on the intercellular pathway.For the blood flow dependent drug absorption, simultaneous luminal and vascular perfusion using the perfluorochemical emulsion as a vascular perfusate was examined. This emulsion was found to retain its normal barrier functions for drug transport. The contribution of blood flow resistance to total resistance of antipyrine absorption exceeded that for salicylic acid absorption. The effects of albumin the vascular perfusate on drug absorption is now under investigation from the direct action of albumin on the capillary wall. Less