Adjuvants and enhancers

Transport from the rectal epithelium primarily involves two transport processes: paracellular and transcellular routes. As in other parts of the gut, the opening of tight junctions by absorption enhancers has been extensively investigated. Putative enhancers include enamine derivatives, salicylates, calmodulin inhibitors, surfactants, chelating agents, fatty acids and lectins. It is generally agreed that the rectum is potentially an important route

0 Distance (cm) 20

Figure 7.11 Spreading of a Witepsol suppository expressed as activity-distance plots as a function of time without (left) and with neostigmine (right)

0 Distance (cm) 20

0 Distance (cm) 20

Figure 7.11 Spreading of a Witepsol suppository expressed as activity-distance plots as a function of time without (left) and with neostigmine (right)

for peptide absorption, although enhancers would be required to increase flux through this region. For example, bioavailability of a small peptide such as vasopressin is increased to nearly 30% in the presence of sodium taurodihydrofusidate. It should always be borne in mind that the enhancement via the paracellular route is non-selective, with the risk of absorption of bacterial endotoxins caused by lysis of bacterial cell walls.

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