From the Guidelines
The key step that prevents bile acids from being reabsorbed once secreted into the small bowel is the interruption of the enterohepatic circulation (EHC) of bile acids by inhibition of bile acid reabsorption in the terminal ileum. This process can be achieved through various mechanisms, including the use of bile acid sequestrants such as cholestyramine, which forms an insoluble complex with bile acids in the intestine, thereby interrupting the EHC 1. However, the most effective method is through the use of IBAT inhibitors, such as Maralixibat and Odevixibat, which inhibit the ileal bile acid transporter (IBAT) and prevent the reabsorption of bile acids in the terminal ileum 1. The use of IBAT inhibitors has been shown to be effective in decreasing cholestatic pruritus and/or circulating bile acids, with a variable range of efficacy depending on the type of progressive familial intrahepatic cholestasis (PFIC) and partially on genotype 1. Key points to consider include:
- The importance of interrupting the EHC of bile acids to prevent their reabsorption
- The role of bile acid sequestrants, such as cholestyramine, in forming an insoluble complex with bile acids
- The efficacy of IBAT inhibitors, such as Maralixibat and Odevixibat, in inhibiting the reabsorption of bile acids in the terminal ileum
- The variable range of efficacy of IBAT inhibitors depending on the type of PFIC and genotype.
From the FDA Drug Label
Colestipol hydrochloride binds bile acids in the intestine forming a complex that is excreted in the feces This nonsystemic action results in a partial removal of the bile acids from the enterohepatic circulation, preventing their reabsorption. Cholestyramine resin adsorbs and combines with the bile acids in the intestine to form an insoluble complex which is excreted in the feces. This results in a partial removal of bile acids from the enterohepatic circulation by preventing their absorption Colesevelam hydrochloride, the active pharmaceutical ingredient in colesevelam hydrochloride, is a non-absorbed, lipid-lowering polymer that binds bile acids in the intestine, impeding their reabsorption
The key step that prevents bile acids from being re-absorbed once they are secreted into the small bowel is binding of bile acids by drugs such as colestipol hydrochloride, cholestyramine resin, and colesevelam hydrochloride, which form a complex that is excreted in the feces, thus preventing their reabsorption 2, 3, 4.
- Main mechanism: Binding of bile acids in the intestine
- Result: Prevention of bile acid reabsorption and removal from the enterohepatic circulation
- Key drugs involved:
- Colestipol hydrochloride
- Cholestyramine resin
- Colesevelam hydrochloride
From the Research
Mechanism of Bile Acid Sequestration
The key step that prevents bile acids from being re-absorbed once they are secreted into the small bowel is the binding of bile acids to bile acid sequestrants.
- Bile acid sequestrants, such as cholestyramine, colestipol, and colesevelam, are positively charged non-digestible resins that bind to bile acids in the intestine to form an insoluble complex 5, 6, 7.
- This complex is then excreted in the feces, preventing the re-absorption of bile acids into the bloodstream.
- The binding of bile acids to bile acid sequestrants is a critical step in the prevention of bile acid re-absorption, as it allows for the removal of excess bile acids from the body 8, 9.
Types of Bile Acid Sequestrants
There are several types of bile acid sequestrants, including:
- Amphiphilic copolymers
- Cyclodextrin/poly-cyclodextrin
- Molecular imprinted polymers
- Each type of bile acid sequestrant has a different level of ability to bind to bile acids, stability, and in-vivo activity 9.
Clinical Applications
Bile acid sequestrants have several clinical applications, including: