Fenofibrate

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Fenofibrate
Systematic (IUPAC) name
1-methylethyl2-[4-(4-chlorobenzoyl) phenoxy]- 2-methyl-propanoate
Identifiers
CAS number	49562-28-9
ATC code	C10AB05
PubChem	3339
DrugBank	APRD00405
Chemical data
Formula	C20H21ClO4
Mol. mass	360.831 g/mol
SMILES	eMolecules & PubChem
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 by Solvay Pharmaceutical in 2005. 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 by Abbott Labs and Lipanthyl by Solvay Pharmaceutical.

Contents 1 Dosage 2 Mode of action 3 Recent updates 4 References

[edit] Dosage

The pharmaceutical form and the strength may change from one country from 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] 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

Like the other fibrates, fenofibrate acts on PPARα to reduce cholesterol levels. The active ingredient in fenofibrate is fenofibric acid. 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 change in overall cardiovascular events, as well as improving some microvascular complications of diabetes.^[3] 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] References

1. ^ 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. 
2. ^ Abbott's request to dismiss antitrust charge over Tricor rejected. FDANews, Drug Daily Bulletin, (June 1, 2006) [1]
3. ^ 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:10.1016/S0140-6736(05)67667-2. PMID 16310551. 

v • d • e Lipid modifying agents (C10) Statins Atorvastatin • Cerivastatin‡ • Fluvastatin • Lovastatin • Mevastatin • Pitavastatin • Pravastatin • Rosuvastatin • Simvastatin Fibrates Clofibrate‡ • Bezafibrate • Aluminium clofibrate • Gemfibrozil • Fenofibrate • Simfibrate • Ronifibrate • Ciprofibrate • Etofibrate • Clofibride Bile acid sequestrants Colestyramine • Colestipol • Colextran • Colesevelam Niacin and derivatives Niceritrol • Niacin • Nicofuranose• Aluminium nicotinate• Nicotinyl alcohol • Acipimox CETP inhibitors Anacetrapib† • Torcetrapib§ Combinations Niacin/lovastatin • Niacin/simvastatin • Ezetimibe/simvastatin Other Dextrothyroxine • Probucol • Tiadenol • Benfluorex • Meglutol • Omega-3-triglycerides • Magnesium pyridoxal 5-phosphate glutamate • Policosanol • Ezetimibe • Laropiprant†, Lapaquistat§ †Undergoing clinical trials. ‡Withdrawn from market. §Development terminated.