Ex vivo permeability experiments in excised rat intestinal tissue and in vitro solubility measurements in aspirated human intestinal fluids support age-dependent oral drug absorption
Ex vivo permeability experiments in excised rat intestinal tissue and in vitro solubility measurements in aspirated human intestinal fluids support age-dependent oral drug absorption
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DOI：
10.1016/j.ejps.2009.10.005
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发表时间：
2010-01-31
影响因子：
4.6
通讯作者：
Augustijns, Patrick
中科院分区：
文献类型：
--
作者：
Annaert, Pieter;Brouwers, Joachim;Augustijns, Patrick
通过测定衰老对(i)从两个年龄组（18-25岁；62-72岁）获得的模型药物在人体肠液（HIF）中的溶解度的影响，研究高龄对肠道药物吸收的可能影响；（ii）模型药物在青年、成年和老年大鼠肠组织中的经上皮渗透。从两个年龄组抽取的HIF中10种难溶性化合物的平均平衡溶解度值显示出很高的个体差异，但没有显示出显著差异。两个年龄组的HIF特征表明pH值具有可比性，而个体胆盐浓度在个体之间表现出明显的差异，但在年龄组之间没有统计学差异。老年大鼠（38周龄）美托洛尔的经上皮渗透明显增加，p -糖蛋白在成年大鼠和老年大鼠中观察到他替洛尔经上皮转运的调节作用，而在年轻大鼠中没有。总之，与年轻人相比，年龄依赖性肠组织通透性（而不是年龄依赖性腔内药物溶解度）可能导致老年患者肠道药物吸收改变。(C) 2009 Elsevier B.V.版权所有
The possible influence of advanced age on intestinal drug absorption was investigated by determining the effects of aging on (i) solubility of model drugs in human intestinal fluids (HIF) obtained from two age groups (18-25 years; 62-72 years); and (ii) transepithelial permeation of model drugs across intestinal tissue excised from young, adult and old rats. Average equilibrium solubility Values for 10 poorly soluble compounds in HIF aspirated from both age groups showed high interindividual variability, but did not reveal significant differences. Characterization of the HIF from both age groups demonstrated comparable pH profiles, while concentrations of individual bile salts showed pronounced variability between individuals, however without statistical differences between age groups. Transepithelial permeation of the transcellular probe metoprolol was significantly increased in old rats (38 weeks) compared to the younger age groups, While the modulatory role of P-glycoprotein in transepithelial talinolol transport was observed in adult and old rats but not in young rats. In conclusion, age-dependent permeability of intestinal tissue (rather than age-dependent luminal drug solubility) may contribute to altered intestinal drug absorption in older patients compared to Young adults. (C) 2009 Elsevier B.V. All rights reserved.