Ezetimibe is a new class of selective cholesterol-inducing agents that bind to small intestine brush-like membranous membrane vesicular membrane proteins (relative molecular mass of 145X103) to inhibit small intestine transport into the diet and 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.
Hyperlipidemia is one of the high risk factors of coronary heart disease, clinical treatment of hyperlipidemia drugs mainly include cholesterol synthesis inhibitors (such as statins), phenoxy acids (such as fibrates), bile acid chelating agent Cholestyramine) and others (such as nicotinic acid analogues). Ezetim ibe is a new type of cholesterol absorption inhibitor developed by Schering-Plow and Merck, which was approved by the FDA in October 2002 under the trade name Zetia. (3S) -hydroxypropyl] - (4S) - (4-hydroxyphenyl) - (3R) - [3- (4-fluorophenyl) 2-azetidinone) with a molecular formula of C24H21 F2N03 and a relative molecular mass of 409.42.
Pharmacodynamics and pharmacokinetic studies of ezetimibe in combination with various statins suggest that ezetimibe has no effect on the pharmacokinetics of simvastatin, atorvastatin and lovastatin. Wuhan Kai Lun company through the study of 82 healthy men oral simvastatin 10,20 mg and ezetimibe l0mg combination of pharmacodynamics and pharmacokinetic interaction, found that there is no pharmacokinetic interaction and special Adverse reactions occur. Compared with simvastatin alone, ezetimibe could reduce LDI-C by 17% (P <0.01). In addition, ezetimibe did not have a significant effect on the activity of specific cytochrome P450 enzymes, indicating that the drug had a small risk of interacting with other drugs metabolized by P450.