Mibeaz Mechanism of Action

Pharmacology: Pharmacodynamics: Ezetimibe, a cholesterol absorption inhibitor, is an antilipemic agent that differs chemically and pharmacologically from other currently available antilipemic agents. Following absorption, the drug localizes at the brush border of the small intestine and inhibits absorption of cholesterol through the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), resulting in decreased delivery of intestinal cholesterol to the liver. This causes a reduction in hepatic cholesterol stores, a compensatory increase in hepatic uptake of cholesterol from systemic circulation, and consequently, an increase in systemic clearance of cholesterol. Moreover, this decreases total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), and triglyceride while increasing HDL-cholesterol.
Pharmacokinetics: Peak plasma concentrations of ezetimibe occur within 4 to 12 hours after an oral dose of ezetimibe. The effect of ezetimibe will present in approximately 2 weeks after therapy initiation. Its oral bioavailability is variable. It was found that food does not appear to affect the extent of absorption of ezetimibe. However, concomitant administration of the drug with a high-fat meal resulted in a 38% increase in peak plasma concentrations of the drug. Ezetimibe is rapidly absorbed when given orally and undergoes extensive conjugation in the small intestine and liver to ezetimibe glucuronide. Ezetimibe and its glucuronide metabolites constitutes 10-20% and 80-90% respectively, of the total absorbed drug in plasma. Both ezetimibe and ezetimibe glucuronide are more than 90% bound to plasma proteins. Ezetimibe and ezetimibe glucuronide are each slowly eliminated from plasma with a half-life of approximately 22 hours. After an oral dose, about 78% is excreted in the feces, mainly as ezetimibe, and about 11% is excreted in the urine, mainly as the glucuronide.