The Intestinal Mucosa as a Physical and Biochemical Barrier to Drug Absorption

The Intestinal Mucosa as a Physical and Biochemical Barrier to Drug Absorption 

Intestinal Metabolism Intestinal drug metabolism can occur by microflora present in the gut lumen, as well as by enzymes present in luminal fluids and in the intestinal mucosa [166], Metabolism of xenobiotics by gut microflora is low in comparison to metabolism by the gut mucosa and liver [62], However, the intestinal microflora (e.g., Bacteroides and Bifidobacteria) may play an important role in the first-pass metabolism of compounds that are poorly or incompletely absorbed by the gut mucosa, especially in the lower parts of the intestine. This bacterial metabolism is largely degradative, 

The example of amprenavir, an HIV-1 protease inhibitor, shows that intestinal metabolism can also be used as a strategy to enhance the bioavailability of compounds. In the biopharmaceutics classification system (BCS), amprenavir can be categorized as a class II compound it is poorly soluble but highly permeable [51]. Fosamprenavir, the water-soluble phosphate salt of amprenavir, on the other hand, shows poor transepithelial transport. However, after oral administration of fosamprenavir, this compound is metabolized into amprenavir in the intestinal lumen and in the enterocytes mainly by alkaline phosphatases, resulting in an increased intestinal absorption [51, 174], 

Different food components (e.g., fruit extracts) and commonly used pharmaceutical excipients (e.g., Tween 80) can interfere with secretory transport systems, leading to drug-food interactions [31, 43, 46, 167], As for CYPs, inhibition and induction of efflux transporters have been reported as possible 

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