biliary excretion

The liver is not only a chemical workshop; it is also a drainage pump. Alongside metabolising drugs, liver cells can pour drug and its metabolites into bile, the green digestive fluid stored in the gallbladder. Bile is released into the intestine, so this route ultimately delivers the drug to the gut.

Hepatocytes use active transporters on their surface to move drug into the tiny bile channels against a concentration gradient. The route favours larger molecules and certain conjugates, especially glucuronides, and it is the main exit for several molecular weight thresholds and for many compounds too big for efficient renal handling.

An important twist follows. Once a drug reaches the gut in bile, it may be reabsorbed back into the blood, sometimes after gut bacteria cleave off a conjugated group. This recycling, called enterohepatic circulation, can prolong a drug's stay in the body and produce a second peak in its plasma concentration.