3.23 : Drug Elimination: Non-Renal Routes

The liver plays a pivotal role in eliminating drugs and their metabolites, primarily through a process known as biliary excretion. This process involves the hepatocytes, the primary cells in the liver that generate bile. A range of transporters actively expels polar drugs or hydrophilic drug metabolites into the bile, which transports the drugs and metabolites into the small intestine. From here, they are eventually expelled from the body through feces. In some instances, the original drug or a drug resulting from the hydrolysis of metabolites by gut microflora may be reabsorbed from the intestine. The reabsorbed drugs are then transported back to the liver, where they are again secreted via bile into the intestine. This cycle is known as enterohepatic circulation. While this recirculation can often prolong the action of a drug, it also raises the potential for drug toxicity. However, the liver is not the only route for drug elimination. Other methods include excretion via breast milk, the lungs, and saliva. Drugs that are excreted through breast milk can have potentially harmful effects on nursing infants. Anesthetic gases are typically eliminated through the lungs, while lipophilic and nonionized drugs are generally excreted through saliva. These drugs diffuse through the epithelial cells of the salivary gland, making saliva an essential medium for drug elimination.