Biotransformation intestinal epithelium

Drugs are transported in the aqueous phase of blood plasma. To have an effect, drugs must enter cells or reach cell membrane receptors. All aspects of the absorption, distribution, biotransformation and elimination of drugs involve transfer across cell membranes. Other barriers, including multiple layers of cells (e.g. the intestinal epithelium or epidermis), also exist. 

All drugs administered to a patient are subject to biotransformation. Orally administered drugs are first subjected to metabolism by the intestinal epithelium and, upon absorption into the portal circulation, metabolized by the liver before entering the systemic circulation. While multiple tissues have certain degree of biotransformation capacity, it is generally accepted that hepatic metabolism represent the most important aspect of drug metabolism. 

Drug distribution in such sites or compartments is a complex process that depends on the systemic circulation concentration and subsequent passage across single cell endothelial or epithelial membranes with specialized physical and molecular barrier functionality. For certain orally administered AIDS medications (e.g., zidovudine and didanosine), oral absorption is limited because of poor absorption from the G1 tract, enzymatic biotransformation in the intestinal epithelium, or first-pass effects (Sinko et al., 1995, 1997). For other AIDS drugs (e.g., protease inhibitors), oral absorption may be complete however, drug distribution into the brain is limited by drug efflux proteins, which promiscuously interact and translocate lipophilic substrates back into blood as they diffuse into the BBB endothelium (Edwards et al., 2005 Kim et al., 1998). 

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