Ezetimibe A New Class Of Selective Cholesterol Absorption Inhibitors

Ezetimibe is a new class of selective cholesterol absorption inhibitors that bind to small intestine brush-like membranous membrane vesicular membrane protein (relative molecular mass of 145X103) to inhibit the small intestine from feeding to and feeding through the bile into the intestine Of cholesterol absorption, lower serum and liver cholesterol levels. Unlike cholic acid chelating agents, ezetimibe does not affect the absorption of cholesterol esters, other steroids (such as bovine cholic acid), triglyceride and fat-soluble vitamins. The pharmacological effects were not related to the inhibition of acetyl-CoA-cholesterol acetyltransferase (ACAT) and the expression of LDL receptor (scavenger receptor). Ezetimibe is absorbed in the liver after combined with glucuronic acid by the hepatic bowel cycle, almost specifically located in the small intestinal mucosal cells.

Rat radioisotope experiments confirmed that ezetimibe had no direct effect on the synthesis of cholesterol in the small intestine and liver and could only be achieved by preventing exogenous cholesterol from enterocyte growth into the cholesterol pool ), Inhibit the transfer of exogenous cholesterol to the lymph, but does not affect the synthesis of cholesterol (endogenous) synthesis into the small intestine of the lipoprotein. Ezetimibe can also inhibit the absorption of phytosterols, becoming the first treatment of rare hereditary plant steroids treatment.

Clinical evaluation

Ezetimibe alone was used in a randomized, double-blind trial of 190 patients with hypercholesterolemia compared with daily oral administration of ezetimibe 1,6,25,100,200,400 mg · kg-1 , 8 weeks of continuous treatment and found that patients with ezetimibe plasma LDL-C in a dose-dependent manner decreased, compared with the baseline level, LDL-C decreased range of 0.6% -15.5%, total cholesterol is also significant The effects of ezetimibe l0mg · d-1 on plasma lipid in patients with primary hypercholesterolemia were studied. The results showed that this product could significantly reduce the level of LDI-C The Ⅱ, Ⅲ clinical trials show that ezetimibe has good safety and tolerance, and found that the best effect of l0mg · d-1, can reduce LDL-C 18.5%, increased HDL-C 3.5 %, And showed a tendency to lower triglyceride (-4.9%).

The pharmacodynamics and pharmacokinetics of ezetimibe in combination with statins also demonstrate that ezetimibe can be associated with statins or fibrates (such as fenofibrate) Combined to achieve better clinical efficacy. A number of scholars on ezetimibe and atorvastatin, pravastatin, lovastatin and simvastatin combined with the pharmacodynamic situation of the study found that ezetimibe and the above four drugs in combination, Have a good synergistic effect, and the drug combination of good tolerance and safety, and its adverse reactions similar to placebo. Pharmacokinetics, ezetimibe on simvastatin and atorvastatin metabolism did not significantly affect. Because ezetimibe does not cause hyperacylglycerol disease in patients with disease progression, clinically can be used alone can not tolerate other lipid-lowering drugs in patients, can also be used with statins can not tolerate high-dose statins patient. Clinically reported ezetimibe adverse reactions are slightly rare, more common is the allergic reaction, facial and glossopharyngeal edema, may cause breathing and swallowing difficulties; sometimes rash, occasionally gastrointestinal discomfort and fatigue The In short, ezetimibe is a new type of cholesterol absorption inhibitor, with excellent pharmacological activity and safety, is the field of blood lipid pharmacological effects of a relatively new category, with a wide range of market prospects. Nevertheless, the long-term effects of ezetimibe on the morbidity and mortality of cardiovascular disease remain to be further examined in the future.