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Ezetimibe



Ezetimibe
Systematic (IUPAC) name
(3R,4S)-1-(4-fluorophenyl)-
3-((3S)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-
(4-hydroxyphenyl)-2-azetidinone
Identifiers
CAS number 163222-33-1
ATC code C10AX09
PubChem 150311
DrugBank APRD00619
Chemical data
Formula C24H21F2NO3 
Mol. mass 409.4 g.mol-1
Pharmacokinetic data
Bioavailability 35–65%
Protein binding >90%
Metabolism Intestinal wall, hepatic
Half life 19–30 hours
Excretion Renal 11%, faecal 78%
Therapeutic considerations
Pregnancy cat.

C (Au), C (U.S.)

Legal status

S4 (Au), POM (UK), ℞-only (U.S.)

Routes Oral

Ezetimibe (pronounced /ɛˈzɛtəmɪb/) is an anti-hyperlipidemic medication which is used to lower cholesterol levels. It acts by decreasing cholesterol absorption in the intestine. It may be used alone when other cholesterol-lowering medications are not tolerated, or together with statins (e.g. ezetimibe/simvastatin) when cholesterol levels are unable to be controlled on statins alone. It is marketed by Schering-Plough and Merck under the trade names Ezetrol, Zetia and Ezemibe. Ezetimibe was originally discovered by a team of four Schering-Plough research chemists; Drs. Stuart B. Rosenblum, Duane A. Burnett, John W. Clader and Brian A. McKittrick.

Additional recommended knowledge

Contents

Pharmacology

Ezetimibe localises at the brush border of the small intestine, where it inhibits the absorption of cholesterol from the diet. Specifically, it appears to bind to a critical mediator of cholesterol absorption, the Niemann-Pick C1-Like 1 (NPC1L1) protein on the gastrointestinal tract epithelial cells[1] as well as in hepatocytes[2]. In addition to this direct effect, decreased cholesterol absorption leads to an increase in LDL-cholesterol uptake into cells, thus decreasing levels in the blood plasma.

Clinical use

Indications

Ezetimibe is indicated as an adjunct to dietary measures in the management of:

  • Hypercholesterolaemia
  • Homozygous sitosterolaemia (phytosterolaemia)[3]

On 9 June 2006, U.S. regulators approved the use of ezetimibe in combination with fenofibrate to treat mixed hyperlipidaemia.

Adverse effects

Common adverse drug reactions (≥1% of patients) associated with ezetimibe therapy include: headache and/or diarrhea. Infrequent adverse effects (0.1–1% of patients) include: myalgia and/or raised liver function test (ALT/AST) results. Rarely (<0.1% of patients), hypersensitivity reactions (rash, angioedema) or myopathy may occur.[3]

 

Dosage forms

Ezetimibe is available as 10 mg tablets in most markets. A combination preparation ezetimibe/simvastatin, which combines ezetimibe with a statin, is also available.

References

  1. ^ Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A 2005;102(23):8132-7. PMID 15928087
  2. ^ Temel, Ryan E., Tang, Weiqing, Ma, Yinyan, Rudel, Lawrence L., Willingham, Mark C., Ioannou, Yiannis A., Davies, Joanna P., Nilsson, Lisa-Mari, Yu, Liqing. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe J. Clin. Invest. 2007 0: JCI30060
  3. ^ a b Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3

See also

 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Ezetimibe". A list of authors is available in Wikipedia.
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