Drug Groups

approved

Description

Ezetimibe is an anti-hyperlipidemic medication which is used to lower cholesterol levels. Specifically, it appears to bind to a critical mediator of cholesterol absorption, the Niemann-Pick C1-Like 1 (NPC1L1) protein on the gastrointestinal tract epithelial cells as well as in hepatocytes.

Indication

For use as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia.

Pharmacology

Ezetimibe is in a class of lipid-lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. Ezetimibe, administered alone is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia. It is also used in combination therapy with HMG-CoA reductase inhibitors. Ezetimibe has a mechanism of action that differs from those of other classes of cholesterol-reducing compounds (HMG-CoA reductase inhibitors, bile acid sequestrants, fibric acid derivatives, and plant stanols). Ezetimibe does not inhibit cholesterol synthesis in the liver, or increase bile acid excretion but instead localizes and appears to act at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood; this distinct mechanism is complementary to that of HMG-CoA reductase inhibitors.

Affected Organisms

Biotransformation

Hepatic, intestinal wall

Half Life

22 hours

Protein Binding

>90%

Elimination

Ezetimibe is primarily metabolized in the small intestine and liver via glucuronide conjugation (a phase II reaction) with subsequent biliary and renal excretion. In humans, ezetimibe is rapidly metabolized to ezetimibe-glucuronide.

References

External Links