Intestinal absorption aspect of non-lipophilic low molecular weight drugs: a case of cephalexin and cefazolin.
Intestinal absorption aspect of non-lipophilic low molecular weight drugs: a case of cephalexin and cefazolin.
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非亲脂性小分子药物的肠道吸收：以头孢氨苄和头孢唑啉为例。
DOI：
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发表时间：
1977
影响因子：
1.7
通讯作者：
S. Muranishi
中科院分区：
文献类型：
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作者：
M. Yasuhara;Y. Miyoshi;A. Yuasa;T. Kimura;S. Muranishi
使用原位再循环技术研究了头孢菌素的吸收特性。头孢氨苄是一种吸收良好的头孢菌素，而头孢唑林是一种吸收较差的头孢菌素，被选为模型化合物。头孢氨苄在等电区的吸收比在碱性 pH 下快得多。 pH 吸收曲线与 pH 分配行为不一致。头孢氨苄的吸收量是头孢唑啉的4.6倍。这种差异无法用 pH 分配假说来解释。研究了头孢菌素的表面活性，它们对吸收特性的贡献很小。研究了头孢菌素从水性卵磷脂脂质体分散体中的转移率。头孢氨苄的膜转移速率明显快于头孢唑林，并且用大鼠肠道总脂质制备脂质体也得到相似的结果。头孢氨苄跨脂质双层转移速率的 pH 曲线与 pH 吸收曲线相似。研究表明，由肠总脂质制备的脂质体以及卵磷脂脂质体是研究这些药物分子跨肠膜转移的合适且有效的模型。
Absorption characteristics of cephalosporins were investigated using in situ recirculation technique. Cephalexin as a fairly well absorbed cephalosporin, and cefazolin as a poorly absorbed one were selected as model compounds. Absorption of cephalexin was much faster in its isoelectric region than in alkaline pH. The pH-absorption profile was not consistent with the pH-partition behavior. The absorption of cephalexin was as much as 4.6 times of cefazolin. This difference could not be explained by the pH-partition hypothesis. The surface activities of cephalosporins were investigated and their contributions to the absorption characteristics were little. The transfer rate of cephalosporins from aqueous lecithin liposome dispersion was investigated. The membrane transfer rate of cephalexin was markedly faster than cefazolin and similar result was obtained when liposome was prepared from rat intestinal total lipids. The pH-profile of the transfer rate of cephalexin across the lipid bilayers was similar to the pH-absorption profile. It is suggested that liposomes prepared from total lipids of the intestine as well as lecithin liposomes are suitable and efficient models for investigation of the transfer of these drug molecules across the intestinal membrane.