Fagerholm U, Lindahl A, Lennernäs H
Department of Pharmacy, University of Uppsala, Sweden.
J Pharm Pharmacol. 1997 Jul;49(7):687-90. doi: 10.1111/j.2042-7158.1997.tb06093.x.
Because the absorption of orally administered drugs depends on intestinal permeability, we have investigated how absorptive capacity varies from the proximal to distal intestine in rats. The effective permeabilities of compounds with a range of physicochemical properties and different absorption mechanisms were estimated by use of a previously validated in-situ, single-pass perfusion model. The low colonic permeabilities of D-glucose and L-dopa indicate the absence or low capacity of the glucose- and amino-acid-transporters in this region. With the exception of the small and moderately lipophilic non-steroidal anti-inflammatory drug, naproxen, for which permeability was maintained throughout the intestine, the passive intestinal permeabilities for hydrophilic and lipophilic drugs were approximately twice as high in the jejunum and ileum as in the colon. These observations are in accord with those made in recent studies. However, the reasons for the high colonic permeability of non-steroidal anti-inflammatory drugs, and results obtained in previous animal experiments demonstrating that the colon is the region of the intestine with the highest absorptive capacity were not fully clarified. These data show that the permeability to hydrophilic and lipophilic drugs decreases along the intestine, whereas it is maintained throughout the intestine for the small and moderately lipophilic naproxen. Further investigations are required to clarify the interplay between membrane composition, fluidity and permeability under various conditions in different absorption models.
由于口服药物的吸收取决于肠道通透性，我们研究了大鼠从近端小肠到远端小肠的吸收能力如何变化。通过使用先前验证过的原位单通道灌注模型，估算了具有一系列物理化学性质和不同吸收机制的化合物的有效通透性。D-葡萄糖和L-多巴在结肠的低通透性表明该区域缺乏葡萄糖和氨基酸转运体或其转运能力较低。除了亲脂性适中的小分子非甾体抗炎药萘普生在整个肠道中都保持较高通透性外，亲水性和疏水性药物在空肠和回肠的被动肠道通透性大约是结肠的两倍。这些观察结果与最近的研究一致。然而，非甾体抗炎药结肠通透性高的原因以及先前动物实验表明结肠是肠道中吸收能力最高区域的结果尚未完全阐明。这些数据表明，亲水性和疏水性药物的通透性沿肠道降低，而亲脂性适中的小分子萘普生在整个肠道中通透性保持不变。需要进一步研究以阐明不同吸收模型中各种条件下膜组成、流动性和通透性之间的相互作用。
