Equilibrium and kinetic factors influencing bile sequestrant efficacy.
Equilibrium and kinetic factors influencing bile sequestrant efficacy.
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影响胆汁螯合剂功效的平衡和动力学因素。
DOI：
10.1023/a:1015862329303
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发表时间：
1992
影响因子：
3.7
通讯作者：
Amidon,GL
中科院分区：
文献类型：
--
作者：
Luner,PE;Amidon,GL
使用考来烯胺进行体外胆盐结合平衡和动力学研究，以确定这些因素如何影响体内胆汁螯合剂功效。与不存在盐的情况下的结合相比，生理浓度的氯离子在一定的 GCH 浓度范围内导致甘胆酸 (GCH) 结合减少两倍以上，并且还观察到会取代结合的 GCH。此外，使用氯选择性电极测量由于胆盐结合而从考来烯胺置换的氯离子，结果表明胆盐结合是由于离子交换造成的。平衡结合实验的结果与人类数据的比较表明，单独的阴离子结合竞争的影响不能解释考来烯胺缺乏功效的原因。根据文献数据，考虑其他影响，例如额外的结合竞争或结合可用性差，表明存在足够的胆汁盐结合潜力，并且这些干扰不是影响树脂功效的主要因素。在动力学研究中，GCH 的结合摄取和氯离子从考来烯胺中置换 GCH 的速度都相对较快，表明考来烯胺应与胃肠道中的胆汁盐快速平衡。基于这些发现，表明考来烯胺的低功效主要是由于其防止回肠中胆汁盐重吸收的能力相对较差。
In vitrobile salt binding equilibria and kinetic studies were performed with cholestyramine to determine how these factors influence bile sequestrant efficacyin vivo. Chloride ion at physiologic concentrations caused more than a twofold reduction in glycocholate (GCH) binding, compared to binding in the absence of salt, over a range of GCH concentrations and was also observed to displace bound GCH. In addition, chloride ion displaced from cholestyramine as a result of bile salt binding was measured using a chloride selective electrode, and the results show that bile salt binding is due to ion exchange. Comparison of the results of the equilibrium binding experiments to human data shows that the effect of anion binding competition alone cannot account for the lack of efficacy of cholestyramine. Consideration of other effects, such as additional binding competition or poor availability for binding, based on data from the literature, shows that adequate bile salt binding potential exists and that these interferences are not major factors influencing resin efficacy. In kinetic studies, both binding uptake of GCH and displacement of GCH from cholestyramine by chloride ion were relatively rapid, indicating that cholestyramine should equilibrate rapidly with bile salts in the GI tract. Based on these findings, it is suggested that the low efficacy of cholestyramine is a result mainly of its relatively poor ability to prevent bile salt reabsorption in the ileum.