22的相关性肠内吸收环孢菌素A:在vitro-in体内相关性。
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弗里克G, Drewe J, Huwyler J,古特曼H, Beglinger C
22的相关性肠内吸收环孢菌素A:在vitro-in体内相关性。
Br J杂志。1996年8月,118 (7):1841 - 7。
- PubMed ID
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8842452 (在PubMed]
- 文摘
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1。环孢菌素之间的相互作用与22(自保”)在肠道吸收研究的结合与人类Caco-2细胞体外实验和插管在健康志愿者学习。2。自保”吸收进入细胞并没有饱和,只表现出较低的温度敏感性,表明被动扩散。当自保”的渗透在Caco-2层从顶端到基底外侧决心,整体运输有一个明显的饱和浓度1 microM组件。在更高浓度渗透over-proportionally增加。基底顶端的动力学参数计算渗透提出了扩散过程与KD 0.5微升最低为1 /过滤器,基底由一个活跃的系统功能使用户顶端方向3.8公里的microM和Jmax 6.5 picomol最低为1 /过滤器。3所示。自保”渗透时更高的药物被基底外侧而渗透细胞的顶面。顶管基底运输自保”是提高长春花碱的存在,道诺霉素和non-immunosuppressive CyA-derivative。 All compounds inhibit p-glycoprotein-mediated transport processes. Basolateral to apical permeation of CyA showed a dose-dependent decrease in the presence of vinblastine. Permeation of daunomycin across Caco-2 cell monolayers was also higher from the basolateral to the apical side than vice versa. Basolateral to apical permeation was decreased in the presence of SDZ PSC 833 and cyclosporin A. 4. Western blot analysis of Caco-2 cells with the monoclonal antibody C219 confirmed the presence of p-glycoprotein in the used cell system. 5. When the absorption of CyA in the gastrointestinal (GI)-tract of healthy volunteers was determined, a remarkable decrease of the plasma AUC could be observed dependent on the location of absorption in the rank order stomach > jejunum/ileum > colon. The decrease in absorption exhibited a marked correlation (r = 0.994) to the expression of mRNA for p-glycoprotein over the GI-tract (stomach < jejunum < colon). 6. All data provide evidence that CyA is a substrate of p-glycoprotein in the GI-tract, which might explain the local differences and the high variability in cyclosporin absorption found in vivo.