Hepatic Drug Excretion: Enterohepatic Cycling

The hepatic biliary system expels drugs and metabolites via bile secretions.

Hepatocytes lining bile canaliculi produce bile that contains water, electrolytes, bile salts, and pigments. Transporters in the hepatocyte membrane move drugs in or out, adding them to bile.

Bile moves to the internal bile ducts, eventually merging into the common hepatic duct. It becomes concentrated in the gall bladder and subsequently released through the cystic duct into the adjoining common bile duct.

Enterohepatic cycling involves the liver releasing bile-containing drugs into the common bile duct, which eventually enters the duodenum. From there, the drug can either be excreted into feces or reabsorbed into the bloodstream, prolonging the drug's activity.

For example, leflunomide, an anti-rheumatoid arthritis drug, follows enterohepatic cycling, causing a hike in systemic drug levels.

To mitigate potential toxic effects, cholestyramine, or activated charcoal, is used to bind the active drug, preventing reabsorption, and enhancing drug elimination.