Faculty of Pharmacy, University of Ljubljana, Askerceva 7, SLO-1000 Ljubljana.
Chem Biodivers. 2009 Nov;6(11):1923-32. doi: 10.1002/cbdv.200900076.
Some examples of pH- and transporter-dependent permeability, determined in side-by-side diffusion cells, are summarized. We investigated the polarized transport in the mucosal-to-serosal direction of monocarboxylic acid-type drugs through the excised rat jejunal tissue and an artificial membrane. We established that, in vitro, these substances are most probably not transported by monocarboxylate transporter 1, but by passive pH-dependent transport. We also studied various influences on the permeability of fluorescein, a low permeability marker, through isolated rat intestinal segments, Caco-2 cell monolayers, and an artificial membrane. Polarized transport of fluorescein in the serosal-to-mucosal direction through the rat jejunum by multidrug resistance-associated protein was triggered by the addition of D-glucose to the mucosal side, while the pH-dependent increase of fluorescein influx is presumably the consequence of a monocarboxylate transporter and a member of the organic-anion transporting polypeptide family. With permeability experiments through the excised segments of rat small intestine, we ascertained that ciprofloxacin is a low-permeability drug and has higher and pH-dependent transport in the mucosal-to-serosal direction than in the opposite direction. We also established that neither the permeability of fluoroquinolones nor their solubility in different buffers was influenced by the interactions with metal cations.
总结了一些通过并排扩散池测定的 pH 和转运体依赖性通透性的实例。我们通过离体大鼠空肠组织和人工膜研究了单羧酸类药物从黏膜侧向浆膜侧的极性转运。我们发现，这些物质在体外极有可能不是通过单羧酸转运蛋白 1 而是通过 pH 依赖性的被动转运进行转运。我们还研究了各种因素对荧光素（低通透性标志物）通过分离的大鼠肠段、Caco-2 细胞单层和人工膜的通透性的影响。多药耐药相关蛋白通过大鼠空肠将荧光素从浆膜侧向黏膜侧进行极化转运，这是由于在黏膜侧添加 D-葡萄糖引起的，而荧光素内流的 pH 依赖性增加可能是单羧酸转运蛋白和有机阴离子转运多肽家族成员的结果。通过离体大鼠小肠段的渗透实验，我们确定环丙沙星是一种低通透性药物，其在黏膜侧向浆膜侧的转运高于相反方向，且具有 pH 依赖性。我们还发现，氟喹诺酮类药物的通透性及其在不同缓冲液中的溶解度均不受与金属阳离子相互作用的影响。
