The process of enterohepatic circulation

Enterohepatic circulation refers to the process and phenomenon that drugs pass through bile, then enter the intestine, are reabsorbed in the intestine, and then return to the liver through the portal vein. In other words, this method is used to promote the bile excretion of drugs. The significance of enterohepatic circulation determines the effect of drug excretion from bile, which can play a good role in preventing drugs from staying in the human body for too long and avoiding the problem of drug side effects.

Enterohepatic circulation process

1. Chemical Cycle

This phenomenon mainly occurs in drugs excreted through bile. Some prototype drugs excreted into the intestine through bile, such as strophanthus glycoside G, have high polarity and can rarely be absorbed from the intestine, and most of them are excreted through feces. Some drugs, such as chloramphenicol and phenolphthalein, become more water-soluble after combining with glucuronic acid in the liver, and are secreted into the bile and excreted into the intestines. They are hydrolyzed by intestinal bacterial enzymes to release the original drug, which is then absorbed by the intestines into the liver. Animal experiments have shown that antimicrobial drugs can reduce the enterohepatic circulation of certain drugs by inhibiting intestinal bacteria. The significance of enterohepatic circulation is determined by the excretion rate of drugs in bile. When drugs are absorbed, their excretion is increased. When the amount of bile excretion is large, the enterohepatic circulation can prolong the duration of drug action. If the enterohepatic circulation of the drug can be blocked, the excretion of the drug can be accelerated. If digitoxin poisoning occurs, taking cholestyramine can bind to it in the intestine and block its reabsorption.

2. Biological Cycle

The excretion of drugs and their metabolites through bile is often an active process, and there are three active excretion pathways: acidic, alkaline and neutral. Certain drugs, especially those excreted through bile, can be partially reabsorbed through the intestinal epithelial cells after being discharged into the duodenum through bile. This is manifested in pharmacokinetic terms as a double peak in the drug-time curve and in pharmacodynamic terms as a significantly prolonged effect of the drug. Some conjugated metabolites are excreted into the intestine via bile, where they are hydrolyzed to release the parent drug, which is then reabsorbed to form an enterohepatic circulation[2]. 26% of digitoxin is excreted into the intestine via bile to form enterohepatic circulation, which is only one of the reasons for the long-lasting effect of the drug. Drugs excreted through breast milk, such as morphine, atropine, and ergot alkaloids, may cause poisoning in infants [2].

Overview

The excretion of drugs in the body is mainly carried out through channels such as the kidneys, bile and mammary glands. Drugs are transformed by the liver and can be secreted into the bile as metabolites or unchanged, and discharged into the duodenum through the common bile duct. Part of them is reabsorbed by the small intestine, returns to the liver through the portal vein, and is then discharged into the intestinal cavity through the bile. This cycle repeats itself, forming the enterohepatic circulation.

The significance of enterohepatic circulation is determined by the excretion rate of the drug in bile. When the amount of bile excretion is large, the enterohepatic circulation can prolong the duration of drug action. If the enterohepatic circulation of the drug can be blocked, the excretion of the drug can be accelerated.