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Membrane Permeability in the Gastrointestinal Tract: The Interplay between Microclimate pH and Transporters

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.