Gemfibrozil

Gemfibrozil

Systematic (IUPAC) name
5-(2,5-dimethylphenoxy)-2,2-dimethyl-pentanoic acid
Clinical data
Trade names	Lopid
AHFS/Drugs.com	monograph
MedlinePlus	a686002
Pregnancy category	Category C
Legal status	By Prescription
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	Close to 100%
Protein binding	95%
Metabolism	Hepatic (CYP3A4)
Half-life	1.5 hours
Excretion	Renal 94% Feces 6%
Identifiers
CAS Registry Number	25812-30-0 Y
ATC code	C10AB04
PubChem	CID 3463
IUPHAR ligand	3439
DrugBank	DB01241 Y
ChemSpider	3345 Y
UNII	Q8X02027X3 Y
KEGG	D00334 Y
ChEBI	CHEBI:5296 Y
ChEMBL	CHEMBL457 Y
Chemical data
Formula	C15H22O3
Molecular mass	250.333 g/mol
SMILES O=C(O)C(C)(C)CCCOc1cc(ccc1C)C
InChI InChI=1S/C15H22O3/c1-11-6-7-12(2)13(10-11)18-9-5-8-15(3,4)14(16)17/h6-7,10H,5,8-9H2,1-4H3,(H,16,17)  Y Key:HEMJJKBWTPKOJG-UHFFFAOYSA-N  Y
Y (what is this?)  (verify)

Gemfibrozil is the generic name for an oral drug used to lower lipid levels. It belongs to a group of drugs known as fibrates. It is most commonly sold as the brand name, Lopid. Other brand names include Jezil and Gen-Fibro.

Development history

Gemfibrozil was selected from a series of related compounds synthesized in the laboratories of the American company Parke Davis in the late 1970s. It came from research for compounds that lower plasma lipid levels in humans and in animals. ^[1]

Actions

• Is an activator of peroxisome proliferator-activated receptor-alpha (PPARα), a nuclear receptor that is involved in metabolism of carbohydrates and fats, as well as adipose tissue differentiation. This increase in the synthesis of lipoprotein lipase thereby increases the clearance of triglycerides.

• Preliminary data has shown that gemfibrozil inhibits production of proinflammatory cytokines in addition to its clinically useful lipid-lowering activity, increased survival in BALB/c mice that were already ill from infection by influenza virus A/Japan/305/57 (H2N2). Gemfibrozil was administered intraperitoneally once daily from days 4 to 10 after intranasal exposure to the virus. Survival increased from 26% in vehicle-treated mice (n = 50) to 52% in mice given gemfibrozil at 60 mg/kg/day (n = 46) (P = 0.0026). If this principle translates to patients, a drug already approved for human use, albeit by a different route for another purpose, might be adapted relatively fast for use against influenza, conceivably including human infection with a derivative of the avian H5N1 strain.^[2]

Therapeutic effects

• Reduce triglyceride levels ^[3]
• Reduce very low density lipoprotein (VLDL) levels
• Modest reduction of low density lipoprotein (LDL) levels
• Moderate increase in high density lipoprotein (HDL) levels

Nontherapeutic effects and toxicities

• GI distress
• Musculoskeletal pain
• Increased incidence of gallstone
• Hypokalemia (low blood potassium)
• Increased risk of cancer

Indications

• Hyperlipidemia (Type III): Gemfibrozil is the drug of choice for therapy.
• Hypertriglyceridemia (Type IV): Gemfibrozil, though not as effective as niacin, is better tolerated.

Contraindications and precautions

• Gemfibrozil should not be given to these patients:
  • Hepatic dysfunction

• Gemfibrozil should be used with caution in these higher risk categories:
  • Biliary tract disease
  • Renal dysfunction
  • Pregnant women
  • Obese patients

Drug Interactions

• Anticoagulants: Gemfibrozil potentiates the action of warfarin and indanedione anticoagulants.
• Statin drugs: Concomitant administration of fibrates (including gemfibrozil) with statin drugs increases the risk of muscle cramping, myopathy, and rhabdomyolysis.

References

External links

• DrugBank Gemfibrozil
• NIH Gemfibrozil Drug Info
• Lopid International Study
• Safety of Statins - Circulation. 2004;109:III-50 – III-57
• http://www.ihs.gov/nptc/documents/NPTC%20Lipid%20Review.pdf