Sotalol permeability in cultured-cell, rat intestine, and PAMPA system.
Sotalol permeability in cultured-cell, rat intestine, and PAMPA system.
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DOI：
10.1007/s11095-012-0699-3
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发表时间：
2012-07
影响因子：
3.7
通讯作者：
Zhai, Suo-Di
中科院分区：
文献类型：
--
作者：
Liu, Wei;Okochi, Hideaki;Benet, Leslie Z.;Zhai, Suo-Di
关键词：
通过细胞、大鼠外翻囊和PAMPA渗透性研究阐明BCS与BDDCS系统中索他洛尔的分类。在Madin达比犬肾（MDCK）和MDR 1转染的MDCK（MDCK-MDR 1）细胞系、大鼠外翻肠囊和平行人工膜渗透性试验（PAMPA）系统中进行了研究。在MDCK细胞系（顶端pH变化）和MDCK-MDR 1细胞（有和无P-糖蛋白抑制剂GG 918）中进行3小时转运研究;使用雄性Sprague-Dawley大鼠（300 ~ 350 g）制备外翻囊。在PAMPA研究中，在每个孔中加入不同pH的药物溶液并孵育5小时。通过LC-MS/MS或液体闪烁计数测量样品，并计算表观渗透率（Papp）。索他洛尔在所有培养细胞系、外翻囊和PAMPA系统中均表现出低渗透性。它可能是一种边界线P-糖蛋白底物。PAMPA研究表明，索他洛尔的渗透性随着顶端pH值的升高而增加，而MDCK细胞中的变化要小得多。索他洛尔的低渗透率与其3类BDDCS分配和缺乏体内代谢相关。
To clarify sotalol’s classification in the BCS versus BDDCS systems through cellular, rat everted sac and PAMPA permeability studies. Studies were carried out in Madin Darby canine kidney (MDCK) and MDR1-transfected MDCK (MDCK-MDR1) cell lines, rat everted gut sacs and the Parallel Artificial Membrane Permeability Assay (PAMPA) system. Three-hour transport studies were conducted in MDCK cell lines (with apical pH changes) and MDCK-MDR1 cells (with and without the P-glycoprotein inhibitor GG918); male Sprague-Dawley rats (300 ~ 350 g) were used to prepare everted sacs. In the PAMPA studies, drug solutions at different pH’s were dosed in each well and incubated for 5 hours. Samples were measured by LC-MS/MS, or liquid scintillation counting and apparent permeability (Papp) was calculated. Sotalol showed low permeability in all of the cultured-cell lines, everted sacs and PAMPA systems. It might be a border line P-glycoprotein substrate. The PAMPA study showed that sotalol’s permeability increased with a higher apical pH, while much less change was found in MDCK cells. The low permeability rate for sotalol correlates with its Class 3 BDDCS assignment and lack of in vivo metabolism.
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DOI：
10.1016/j.ejpb.2004.02.007
发表时间：
2004-07-01
影响因子：
4.9
作者：
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