Ezetimibe
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| Ezetimibe
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| 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 | C24H21NF2O3 |
| Mol. weight | 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. | |
| Legal status |
S4 (Au), POM (UK), ℞-only (U.S.) |
| Routes | Oral |
Ezetimibe (IPA: [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 unable to be 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.
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[edit] 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 the Niemann-Pick C1-Like 1 (NPC1L1) protein on the gastrointestinal tract epithelium, a critical mediator of cholesterol absorption.<ref name="Garcia-Calvo2005">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</ref> 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.
[edit] Clinical use
[edit] Indications
Ezetimibe is indicated as an adjunct to dietary measures in the management of:
- Hypercholesterolaemia
- Homozygous sitosterolaemia (phytosterolaemia)<ref name="AMH2006">Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
</ref>
On 9 June 2006, U.S. regulators approved the use of ezetimibe in combination with fenofibrate to treat mixed hyperlipidaemia.
[edit] 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.<ref name="AMH2006" />
[edit] Dosage forms
Ezetimibe is available as 10 mg tablets in most markets, with 5 mg and 20 mg tablets also being available on the U.S. market. A combination preparation ezetimibe/simvastatin, which combines ezetimibe with a statin, is also available.
[edit] References
[edit] See also
[edit] External links
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