Ezetimibe mechanism of action?

How does ezetimibe work (mechanism of action)?

Ezetimibe lowers cholesterol by blocking intestinal cholesterol absorption. It targets the Niemann-Pick C1–like 1 (NPC1L1) transport protein at the brush border of enterocytes (intestinal cells), which reduces uptake of dietary and biliary cholesterol into the body. With less cholesterol absorbed, the liver takes up more cholesterol from the bloodstream, which helps lower LDL cholesterol levels 1.

Does ezetimibe affect absorption of other sterols?

Because it acts on NPC1L1-mediated uptake of cholesterol in the intestine, ezetimibe mainly impacts cholesterol absorption rather than directly changing cholesterol synthesis in the liver. By reducing absorption of cholesterol (and related sterols entering via the intestine), it can also lower total cholesterol and non-HDL cholesterol, though its effect sizes are generally smaller than drugs that strongly suppress hepatic cholesterol synthesis 1.

What are the practical implications for combination therapy?

Ezetimibe is often used with statins because it works through a different pathway: statins mainly reduce cholesterol synthesis in the liver, while ezetimibe reduces cholesterol absorption in the gut. Together, they can produce larger LDL reductions than either mechanism alone 1.

What happens at the molecular level in the gut?

NPC1L1 is responsible for transporting cholesterol from the intestinal lumen into enterocytes. Ezetimibe inhibits this transport step, so less cholesterol enters circulation through the intestinal route 1.

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