Drug Classification of Ezetrol (Ezetimibe)
Ezetrol (ezetimibe) is a selective cholesterol absorption inhibitor that blocks intestinal uptake of dietary and biliary cholesterol by inhibiting the Niemann-Pick C1-Like 1 (NPC1L1) protein at the brush border of the small intestine. 1, 2, 3
Mechanism of Action
Ezetimibe represents a distinct drug class from statins (HMG-CoA reductase inhibitors) and bile acid sequestrants, as it specifically targets the NPC1L1 sterol transporter located at the brush border of enterocytes in the small intestine. 1, 2, 3
The drug localizes at the intestinal wall and prevents luminal cholesterol absorption by blocking the passage of both dietary and biliary cholesterol across the intestinal epithelium, which fundamentally differs from statins that inhibit hepatic cholesterol synthesis and bile acid sequestrants that interrupt enterohepatic circulation. 1, 2, 4
This selective inhibition reduces intestinal cholesterol absorption by approximately 54% in hypercholesterolemic patients, leading to decreased delivery of cholesterol to the liver, upregulation of hepatic LDL receptors, and increased clearance of LDL-cholesterol from the bloodstream. 2, 3
Selectivity Profile
Ezetimibe's mechanism is highly selective for cholesterol and phytosterols, with no clinically meaningful effects on the absorption of fat-soluble vitamins (A, D, E), triglycerides, or bile acids. 1, 2, 3
The drug does not affect adrenocortical steroid hormone production, further demonstrating its specificity for intestinal sterol transport. 3
Clinical Classification Context
In clinical practice and guidelines, ezetimibe is categorized as a "nonstatin LDL-lowering therapy" or "cholesterol absorption inhibitor," distinguishing it from other lipid-modifying drug classes including statins, fibrates, bile acid sequestrants, PCSK9 inhibitors, and bempedoic acid. 1
The American College of Cardiology and American Heart Association consistently classify ezetimibe separately from other lipid-lowering agents due to its unique molecular target and mechanism. 1, 2
Pharmacologic Properties
Ezetimibe is administered as a single 10 mg oral dose daily, with or without food, and undergoes extensive first-pass glucuronidation to form an active metabolite (ezetimibe-glucuronide). 2, 3
The drug has minimal systemic absorption and does not significantly affect cytochrome P450 enzymes, resulting in few drug-drug interactions compared to other lipid-lowering agents. 2, 5