Fenofibrate
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Fenofibrate
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| Systematic (IUPAC) name | |
| propan-2-yl 2-{4-[(4-chlorophenyl)carbonyl]phenoxy}-2-methylpropanoate | |
| Identifiers | |
| CAS number | |
| ATC code | C10 |
| PubChem | |
| DrugBank | |
| ChemSpider | |
| Chemical data | |
| Formula | C20H21ClO4 |
| Mol. mass | 360.831 g/mol |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Protein binding | 99% |
| Metabolism | ? |
| Half life | 20 hours |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
C(US) |
| Legal status | |
| Routes | Oral |
Fenofibrate is a drug of the fibrate class. Fenofibrate was discovered by Groupe Fournier SA, before it was acquired in 2005 by Solvay Pharmaceutical, a business unit owned by the Belgian corporation, Solvay S.A. It is mainly used to reduce cholesterol levels in patients at risk of cardiovascular disease. Like other fibrates, it reduces both low-density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels, as well as increasing high-density lipoprotein (HDL) levels and reducing tryglycerides level. It also appears to have a beneficial effect on the insulin resistance featured by the metabolic syndrome.[1] It is used alone or in conjunction with statins in the treatment of hypercholesterolemia and hypertriglyceridemia. Fenofibrate is sold under the brand name Tricor and Trilipix by Abbott Labs, Lipofen by Kowa Pharmaceuticals America Inc, Lofibra by Teva, Lipanthyl and Lipidil by Solvay Pharmaceutical, Fenocor-67 by Ordain Health Care Pvt Ltd and Fenogal by SMB Laboratories.
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[edit] Dosage
The pharmaceutical form and the strength may change from one country to another, and from one brand to another. In the United States, Tricor was reformulated in 2005 and is available in tablets of 48 and 145 mg. This reformulation is controversial and is the subject of antitrust litigation by generic drug manufacturer Teva.[2] Also available in the United States, Lofibra is available in 54 and 160 mg tablets, as well as 67, 134, and 200 mg micronized capsules[3]. Generic equivalents of Lofibra capsules are currently available in all three strengths in the United States. In Europe, it is available in either coated tablet or capsule; the strength range includes 67, 145, 160 and 200 mg. The differences among strengths are a result of altered bioavailability (the fraction absorbed by the body) due to particle size. For example, 200 mg can be replaced by 160 mg micronized fenofibrate. The 145 mg strength is a new strength appeared in 2005-2006 which also replaces 200 or 160 mg as the fenofibrate is nanonised (ie the particle size is below 400 nm).
[edit] Mode of action
Fenofibrate is a prodrug; its active metabolite, responsible for its effects, is fenofibric acid. Like the other fibrates, fenofibric acid is an agonist of PPARα, which in turn acts to reduce cholesterol levels. Fenofibric acid inhibits the synthesis of cholesterol as well as enhancing its elimination as bile salts, while in addition both inhibiting the synthesis of triglycerides and enhancing their breakdown.
[edit] Recent updates
A large study in 2005 of fenofibrate in patients with diabetes showed no change in total mortality or coronary artery events, but did show a significant reduction in overall cardiovascular events, as well as improving some microvascular complications of diabetes.[4] The decrease in overall cardiovascular effects was documented in FIELD as a 0.7% absolute risk reduction after 5 years of treatment, however a 0.7% increase in the rate of pulmonary embolus was also noted in this trial.
Like most fibrates, fenofibrate can cause stomach upsets and myopathy (muscle pain) and very rarely rhabdomyolysis. This risk is increased when used together with statins. However, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study provides important information that long-term treatment with fenofibrate therapy appears to have a favorable safety profile in patients with type 2 diabetes, even when nonstudy lipid-lowering medications were added. In FIELD, there were no cases of rhabdomyolysis reported in patients on combination therapy with fenofibrate and a statin. Thus, there is an increasing body of evidence that fenofibrate/statin combination therapy is safe and effective at managing dyslipidemia in patients with type 2 diabetes who are at risk for cardiovascular events. Fenofibrate increases the serum level of statins and therefore, a lower dose of statin is generally necessary. Dose of fenofibrate must also be lowered in moderate to severe renal failure and most experts recommend that fenofibrate be given in the morning and the statin at night. Fenofibrate has been shown to decrease progression of albuminuria and diabetic retinopathy.
[edit] Other uses
Fenofibrate has a uricosuric effect, making it of use in the management of gout.[5]
[edit] Notes
- ^ Wysocki J, Belowski D, Kalina M, Kochanski L, Okopien B, Kalina Z (2004). "Effects of micronized fenofibrate on insulin resistance in patients with metabolic syndrome". Int J Clin Pharmacol Ther 42 (4): 212–7. PMID 15124979.
- ^ Abbott's request to dismiss antitrust charge over Tricor rejected. FDANews, Drug Daily Bulletin, (June 1, 2006) [1]
- ^ TEVA Pharmaceutical Lofibra Product Site[2]
- ^ FIELD study investigators (2005). "Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial". Lancet 366 (9500): 1849–61. doi:. PMID 16310551.
- ^ Bardin T (June 2003). "Fenofibrate and losartan". Ann. Rheum. Dis. 62 (6): 497–8. doi:. PMID 12759281. PMC: 1754575. http://ard.bmjjournals.com/cgi/content/full/62/6/497.
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