enterohepatic circulation

Enterohepatic circulation is a recycling loop in which a drug travels from the liver into the gut and then back again, going around several times before finally leaving the body. Picture a drug caught in a revolving door between the intestine and the liver: each lap delays its departure and keeps it in the body longer.

The loop works like this. The liver processes a drug and secretes some of it — often after attaching a sugar-like group (conjugation) to make it water-soluble — into bile, which empties into the small intestine. There, gut bacteria can snip off the added group, regenerating the original fat-soluble drug, which is then reabsorbed across the gut wall, returns to the liver via the portal vein, and the cycle repeats.

The main effect is to prolong a drug's stay in the body, lengthening its half-life and sustaining its blood levels. This can be helpful (longer action from a single dose) but also means the drug lingers longer than its raw clearance would suggest. Drugs that undergo extensive enterohepatic circulation often show a characteristic 'second peak' in their blood concentration after dosing.

The loop can be interrupted on purpose. Giving a substance that binds drug in the gut (such as activated charcoal or a bile-acid binding resin) prevents reabsorption, breaks the cycle, and speeds elimination — a tactic sometimes used to treat overdose or poisoning.