Learning about ezetimibe.📜📜📜

Ezetimibe was the first drug to inhibit cholesterol absorption in the gut. It can be combined with statins to enhance the ability to lower cholesterol levels. It is widely used clinically. The following will introduce the relevant knowledge about ezetimibe.

1. The mechanism of ezetimibe.

Ezetimibe is converted to ezetimibe-glucuronide in the intestinal tract. Ezetimibe-glucuronide acts at the brush border of intestinal epithelial cells. It inhibits the activity of the sterol carrier transporter NPC1L1, thereby reducing intestinal absorption of cholesterol.

Dosage: Once a day, 10mg ezetimibe each time. Ezetimibe can be taken any time of the day. It can also be taken on an empty stomach or with food.

2. The enterohepatic circulation of ezetimibe.

First, ezetimibe is converted to ezetimibe-glucuronide in the intestine. It then travels from the portal vein to the liver and from the liver to the bile. Finally it goes back into the intestines. Enterohepatic circulation maintains ezetimibe-glucuronide in the brush border of intestinal epithelial cells. It can inhibit the intestinal absorption of cholesterol. In addition, enterohepatic circulation can also slow the elimination of ezetimibe-glucuronide. Its half-life is 22 hours.

3. The lipid-lowering intensity of ezetimibe.

Cholesterol in the human body can be divided into endogenous synthesis by the body and exogenous absorption in the diet. About 2/3 of cholesterol is synthesized endogenously and 1/3 of cholesterol is absorbed exogenously. 

Ezetimibe alone can reduce low-density lipoprotein cholesterol (LDL-C) by about 20%. 

	Total cholesterol (TC)	Low-density lipoprotein cholesterol (LDL-C)	High-density lipoprotein cholesterol (HDL-C)	Triglycerides (TG)
Ezetimibe	13%↓	18%↓	8%↓	1%↑
Pravastatin	17%↓	25%↓	8%↓	7%↑
Simvastatin	26%↓	36%↓	17%↓	7%↑
Atorvastatin	32%↓	44%↓	25%↓	4%↑

From the above table, it can be seen that statins have stronger lipid-lowering intensity than ezetimibe. Therefore, ezetimibe is often used in combination with statins to further reduce LDL-C.

	Lipid-lowering treatment plan	Reduced levels of LDL-C
Monotherapy	Ezetimibe	20%
	Moderate-intensity statins (eg, simvastatin, pravastatin)	30%
	High-intensity statins (eg, atorvastatin, rosuvastatin)	50%
	PCSK9 inhibitors (eg, evolocumab, alirocumab)	60%
Combination therapy	High-intensity statin + Ezetimibe	65%
	High-intensity statin + PCSK9 inhibitor	75%
	High-intensity statin + PCSK9 inhibitors + Ezetimibe	85%

4. Adverse reactions.

Because ezetimibe is not metabolized by CYP450 enzymes, it is less likely to have drug interactions. Ezetimibe was well tolerated and safe. Its adverse effects are mild and mostly transient. Its main adverse reactions are gastrointestinal discomfort and headache. In addition, side effects such as muscle pain and increased transaminases can occur when it is used in combination with statins.