Definition
Pharmaceutical agents are excreted primarily in the urine and, via the liver, in the bile in the stool. When excreted via the bile, they re-enter the small intestine, where they may be reabsorbed. They are transported back to the liver via the portal vein. This repetitive process is called the enterohepatic circulation. It prolongs the residence time of the drug in the body and its half-life. Conjugates such as the glucuronides and sulfates can be cleaved by the bacteria of the intestinal flora. In this process, the active ingredients or metabolites are released again and can be reabsorbed. It should be added that many endogenous substances and bile components, such as the bile salts and bilirubin, are also subject to circulation, i.e. they are “recycled”. In this context, too, we speak of enterohepatic circulation. The prerequisite is that the active substances are eliminated hepatically. Substances that are excreted primarily via the kidney and urine are not subject to the enterohepatic circulation, or only to a minor extent.
Examples
Examples of agents that are subject to enterohepatic circulation:
- Ciclosporin
- Colchicine
- Digoxin and related cardiac glycosides.
- Ezetimibe
- Folic acid
- Bile acids, e.g. the ursodeoxycholic acid
- Irbesartan
- Isotretinoin
- Lorazepam
- Methotrexate
- Mifepristone
- Mycophenolate mofetil
- NSAIDs such as diclofenac, piroxicam and indomethacin.
- Estrogens
- Progesterone
- Vitamin B12
- Warfarin
Interactions
Drug-drug interactions can occur when the active ingredients are bound in the intestine and sent for excretion, for example, by activated charcoal or colestyramine. Typical examples of agents with an enterohepatic circulation are the estrogens such as ethinylestradiol, which is contained in hormonal contraceptives. During antibiotic use and diarrhea, the enterohepatic circuit can potentially be interrupted. Estrogen concentration decreases, which may lead to unwanted pregnancy. Diseases of the hepatic and biliary tracts can also lead to impairment of the enterohepatic circulation and thus have an impact on the pharmacokinetics of the drugs involved.
