IBAT inhibitors are oral medications that influence how the body processes bile acids. They target a pathway involved in bile acid recycling, altering their circulation to provide therapeutic effects for various medical conditions.
Understanding Bile Acids and Their Role
Bile acids are compounds synthesized in the liver from cholesterol. They are then stored and concentrated in the gallbladder between meals. When food enters the small intestine, especially fats, the gallbladder releases bile containing these acids into the duodenum.
Bile acids play a role in digestion by breaking down and absorbing dietary fats and fat-soluble vitamins. After digestion, about 95% of bile acids are reabsorbed in the terminal ileum. The reabsorbed bile travels back to the liver via the portal vein, completing enterohepatic circulation.
This enterohepatic circulation is an efficient recycling system, allowing reuse. Only about 5% of bile acids are excreted in the feces daily. The liver produces new bile acids to compensate for this loss, maintaining a stable pool.
How IBAT Inhibitors Work
IBAT inhibitors target the ileal bile acid transporter (IBAT), located in the terminal ileum. This transporter is responsible for the active reabsorption of conjugated bile acids from the gut into the bloodstream.
By blocking this transporter, IBAT inhibitors prevent bile acid reabsorption in the small intestine. This leads to an increase in bile acids that continue into the colon and are excreted in the stool. The reduced return of bile acids to the liver prompts the liver to increase its production of new bile acids.
This increased demand for new bile acid synthesis consumes more cholesterol in the liver. Consequently, the overall pool of bile acids circulating between the liver and intestine is reduced, and the body’s cholesterol levels can be impacted. The therapeutic effects of IBAT inhibitors stem from this disruption of bile acid recirculation.
Medical Conditions Treated
IBAT inhibitors manage medical conditions characterized by bile acid accumulation. They treat cholestatic pruritus, severe itching caused by impaired bile flow in liver diseases. Conditions like progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome (ALGS) cause intense itching.
In PFIC and ALGS, bile excretion is compromised, leading to bile acid buildup in the liver and bloodstream. By reducing bile acid reabsorption in the intestine, IBAT inhibitors decrease bile acid levels. This alleviates severe itching.
IBAT inhibitors, such as odevixibat (Bylvay) and maralixibat (Livmarli), have received approval for treating cholestatic pruritus associated with PFIC and ALGS. Odevixibat is approved for patients as young as 3 months with PFIC, while maralixibat is approved for patients 1 year of age or older with ALGS.
Important Considerations and Side Effects
IBAT inhibitors can cause side effects. Because they increase bile acids in the colon, common gastrointestinal side effects are diarrhea, abdominal pain, and nausea. These symptoms are mild to moderate, but can lead to treatment interruption.
Patients taking IBAT inhibitors require medical supervision. Liver function tests should be monitored regularly due to potential drug-induced liver injury, including elevated liver enzymes. Rarely, some patients have experienced severe liver-related adverse events, including the need for liver transplantation.
IBAT inhibitors are prescription-only medications. Their use requires careful consideration of potential drug interactions and adherence to the regimen. Monitoring for fat-soluble vitamin deficiencies is also advised during prolonged therapy, as altered bile acid circulation can affect absorption.