Enterohepatic cycling involves the active secretion of drugs and their metabolites into the bile via transporters in the canalicular membrane of hepatocytes. This secretion is an integral part of the digestive process, releasing these substances into the gastrointestinal (GI) tract.

Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This phenomenon of enterohepatic cycling significantly extends the duration of a drug's or toxin's presence and its effects within the organism before it is eliminated through other pathways.

Various oral substances interrupt enterohepatic cycling by binding with the bile-excreted metabolites. This intervention could be crucial in managing the effects of certain drugs or toxins. Ultimately, unabsorbed drugs and biliary excretions are expelled from the body through feces.

Enterohepatic circulation becomes particularly important after administering multiple or very high drug doses. This can result in more significant amounts of the drug being secreted in the bile and potentially reabsorbed, impacting absorption and elimination rate constants. It may also lead to saturation of the biliary secretion process, altering the plasma level-time curve.

Drugs undergoing enterohepatic circulation may exhibit a small secondary peak in the plasma drug-concentration curve, indicating reabsorption of biliary-excreted drugs. Bile duct cannulation in animal studies and drug recovery from feces in humans can provide estimates of biliary excretion.