Ezetimibe reduces the amount of cholesterol absorbed by the body. Ezetimibe is used to treat high cholesterol and sometimes given with other cholesterol-lowering medications.
Ezetimibe is a lipid-lowering compound that inhibits intestinal cholesterol and related phytosterol absorption. The discovery and research of this drug began in the early 1990's, where intravenous administration of radio-labelled compound in rats resulting in subsequent localization of the drug within enterocytes at the intestinal villus, leading to studies of investigating the effect of ezetimibe on intestinal cholesterol absorption.
Ezetimibe is used as an adjunctive therapy to diet to lower cholesterol levels in primary hyperlipidemia, mixed hyperlipidemia, homozygous familial hypercholesterolemia (HoFH), and homozygous sitosterolemia (phytosterolemia).
Ezetimibe was shown to reduce the levels of total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG), and increase high-density lipoprotein cholesterol (HDL-C) in patients with hyperlipidemia.
This therapeutic effect was more profound when ezetimibe was co-administered with a statin or fenofibrate compared to either treatment alone.
In clinical trials involving patients with homozygous and heterozygous familial hypercholesterolemia and in those with sitosterolemia, a recommended therapeutic dose of ezetimibe was effective in reducing the LDL levels by 15-20% while increasing HDL-C by 2.5-5%.
Ezetimibe mediates its blood cholesterol-lowering effect via selectively inhibiting the absorption of cholesterol and phytosterol by the small intestine without altering the absorption of fat-soluble vitamins and nutrients.
The primary target of ezetimibe is the cholesterol transport protein Niemann-Pick C1-Like 1 (NPC1L1) protein. NPC1L1 is expressed at the enterocyte/ gut lumen (apical) as well as the hepatobiliary (canalicular) interface and plays a role in facilitating internalization of free cholesterol into the enterocyte in conjunction with the adaptor protein 2 (AP2) complex and clathrin.
Once cholesterol in the gut lumen or bile is incorporated into the cell membrane of enterocytes, it can bind to the sterol-sensing domain of NPC1L1 and form a NPC1L1/cholesterol complex. The complex can then be internalized or endocytosed by joining to AP2 clathrin, forming a vesicle complex that is translocated for storage in the endocytic recycling compartment.
Metabolism: Ezetimibe is rapidly and extensively metabolized via a phase II glucuronide conjugation reaction in the small intestine and liver to form its main phenolic metabolite, ezetimibe glucuronide.
Absorption: Administration of a single 10-mg dose of ezetimibe in fasted adults resulted in a peak plasma concentrations (Cmax) of 3.4 to 5.5 ng/mL were achieved within 4 to 12 hours (Tmax).
Route of elimination: Following oral administration, about 78% and 11% of the administered radio-labelled ezetimibe were recovered in the feces and urine, respectively. Ezetimibe was the major component in feces and accounted for 69% of the administered dose as unconjugated compound, while ezetimibe-glucuronide was the major component in urine and accounted for 9% of the administered dose. High recovery of unchanged parent drug in feces suggests low absorption and/or hydrolysis of ezetimibe-glucuronide secreted in the bile.
Half life: Both ezetimibe and ezetimibe-glucuronide display an approximate half-life of 22 hours
All medicines may cause side effects, but many people have no, or minor, side effects.Some medical conditions may interact with Ezetimibe.
Tell your doctor or pharmacist if you have any medical conditions.
Common ezetimibe side effects may include: muscle or joint pain, stuffy nose, sinus pain, sore throat, diarrhea or pain in an arm or leg.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.
