Diffusional Path in Mucus Layers and Possible Drug Interactions

2 Diffusional Path in Mucus Layers and Possible Drug Interactions 

The thickness of the mucus layer in the human stomach is about 570 pm [101], whereas in the human colon the thickness is about 100-150 pm [102], Ryu and Grim [103] suggested that there is little mixing between the villi and the unstirred layer over the tip of the villi of the canine jejunum, which is about 500-1000 pm thick. Therefore, for a solute to reach the lateral surfaces of the villi, an additional barrier of as much as 800 pm needs to be traversed [103]. It was shown that native mucus gel from rat small intestine reduced the diffusion coefficients of 3H-water, urea, benzoic acid, antipyrine, aminopyrine, alpha-methyl-glucoside, L-phenylalanine by 37%-53% compared with buffer solution [104], For high-molecular-weight substances, such as proteins or microparticulates, mucin can offer considerable resistance to diffusion [105], 

Apart from being a diffusional barrier, mucin can also interact with drugs to decrease their bioavailability, as has been shown with tetracycline [106], phenylbutazone, and warfarin [107]. On the other hand, studies in rats showed that binding of some water-soluble drugs to intestinal mucus was essential for their absorption and that damage to the mucus significantly reduced absorption [108], The acidic mucus is essential for lipid absorption and could be important for the diffusion of lipophilic drugs (see below). 

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