This is the second most important route by which drugs and their metabolites are excreted. Large polar molecules (MW > 300) are often excreted in bile since they are not reabsorbed in the intestine. These drugs cannot diffuse across membranes and are therefore actively transported into bile. The ability of different species to excrete in the bile polar compounds with molecular weights between 300 and 500 varies:
Drugs and drug conjugates entering the gut in bile may be reabsorbed and subsequently excreted in urine or returned to the bile. This occurs particularly with small, less polar drugs. Glucuronide conjugates of drugs may also be cleaved by enzymes in the intestinal microflora (e.g., beta-glucuronidase) to liberate the parent lipid-soluble drug, which is then reabsorbed.
