Kimura T, Sudo K, Kanzaki Y, Miki K, Takeichi Y, Kurosaki Y, Nakayama T
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Biol Pharm Bull. 1994 Feb;17(2):327-33. doi: 10.1248/bpb.17.327.
Profiles of absorption versus drug molecular weight and absorption versus drug lipophilicity were investigated in both the small and large intestines of rats by an in situ loop method. The absorption-molecular weight profiles examined using different-sized polyethylene glycols (PEGs) were different between the small and large intestines; the large-intestinal absorption of PEGs with molecular weights larger than 300 was poor, while PEGs with molecular weights up to 600 were relatively well absorbed in the small intestine. It is suggested that the paracellular route for drug penetration in the large intestine is restricted more than in the small intestine. The absorption-lipophilicity profiles were also examined in various regions (loops of 6 cm) of rat intestine using three acylsalicylic acids, acetyl-, propionyl- and butyrylsalicylic acids. The absorption rates of the acylsalicylic acids were different in the intestinal regions: the jejunum > the ileum > the colon > the rectum. In each region, the absorption rate increased with the drug lipophilicity. However, it was shown that the absorption rates in the small intestine tended to reach a ceiling at the high lipophilicity. To confirm this tendency, the absorption rates of acetaminophen and indomethacin were compared in the four intestinal regions. The absorption rates of highly lipophilic indomethacin were similar in the large and small intestines, while intermediately lipophilic acetaminophen was more rapidly absorbed in the small intestine than in the large intestine. A thicker unstirred water layer adjacent to the small-intestinal mucosa would be one of the factors which cause such varying absorption-lipophilicity profiles.
采用原位肠袢法，在大鼠的小肠和大肠中研究了吸收与药物分子量以及吸收与药物亲脂性的关系。使用不同大小的聚乙二醇（PEG）检测的吸收-分子量关系在小肠和大肠之间存在差异；分子量大于300的PEG在大肠中的吸收较差，而分子量高达600的PEG在小肠中吸收相对较好。这表明药物在大肠中通过细胞旁路途径渗透比在小肠中受到更多限制。还使用三种酰基水杨酸，即乙酰水杨酸、丙酰水杨酸和丁酰水杨酸，在大鼠肠道的各个区域（6厘米长的肠袢）检测了吸收-亲脂性关系。酰基水杨酸在肠道各区域的吸收速率不同：空肠＞回肠＞结肠＞直肠。在每个区域，吸收速率随药物亲脂性增加而升高。然而，结果表明，在高亲脂性时小肠中的吸收速率趋于达到上限。为了证实这种趋势，比较了对乙酰氨基酚和吲哚美辛在四个肠道区域的吸收速率。高亲脂性的吲哚美辛在大肠和小肠中的吸收速率相似，而中等亲脂性的对乙酰氨基酚在小肠中的吸收比在大肠中更快。紧邻小肠黏膜的较厚的未搅动水层可能是导致这种吸收-亲脂性不同关系的因素之一。
