Ezetimibe

Ezetimibe belongs to the group of cholesterol absorption inhibitors and is a lipid-lowering agent used to lower blood cholesterol levels. It is mainly used as an add-on therapy for the treatment of primary hyperlipidemia and in familial hypercholesterolemia.

The discovery and research of ezetimibe began in the early 1990s after intravenous administration of ezetimibe to rats showed that the drug accumulates in the enterocytes of the intestinal villi. This finding prompted studies to investigate the effect of ezetimibe on intestinal cholesterol absorption.

Pharmacodynamics

The cholesterol-lowering effect in the blood is mainly prompted by ezetimibe selectively inhibiting the absorption of cholesterol and phytosterol by the small intestine, but without interfering with the absorption of fat-soluble vitamins and nutrients. Inhibition of transport of lipids into the blood is achieved through inhibited binding to the transport protein NPC1L1. As a result, the amount of circulating cholesterol in the blood is reduced.
Ezetimib senkt neben dem Gesamtcholesterin auch das LDL-Cholesterin, das Apo-B-Protein und Triglyzeride und kann eine Erhöhung des HDL-Cholesterins bewirken.

Pharmacokinetics

Ezetimibe is rapidly absorbed after oral administration and metabolized to its major active metabolite, ezetimibe glucoronide, and subsequently excreted via bile. The highest concentration of ezetimibe in blood plasma is reached after 4-12 hours, that of ezetimibe glucoronide after 1-2 hours, and circulates with approximately 99% (ezetimibe) and approximately 90% (ezetimibe glucoronide) bound to proteins. Elimination occurs in the feces and to a lesser extent in the urine.

Interactions

Interactions may occur with antacids, colestyramine, fibrates, and warfarin, among others.

Side effects

Adverse effects such as abdominal pain, diarrhea, flatulence, or fatigue may occur during treatment with ezetimibe.

Toxicological Data

LD50 (oral and intraperitoneal, rat): > 2000 mg/kg