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Additional information about the drug Gemfibrozil


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.
Contents
1 Development history
2 Actions
3 Therapeutic effects
4 Side effects and toxicities
5 Indications
6 Contraindications and precautions
7 Drug interactions
8 Environmental data
9 References
10 External links
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.
Actions
The exact mechanism of action of gemfibrozil is unknown; however, several theories exist regarding the very low density lipoprotein (VLDL) effect; it can inhibit lipolysis and decrease subsequent hepatic fatty acid uptake as well as inhibit hepatic secretion of VLDL; together these actions decrease serum VLDL levels and increase HDL-cholesterol; the mechanism behind HDL elevation is currently unknown.
Gemfibrozil increases the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis. It does so by activating peroxisome proliferator-activated receptor alpha (PPARα) ‘transcription factor ligand’, a 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. Chylomicrons are degraded, VLDLs are converted to LDLs, and LDLs are converted to HDL. This is accompanied by a slight increase in secretion of lipids into the bile and ultimately the intestine. Gemfibrozil also inhibits the synthesis and increases the clearance of apolipoprotein B, a carrier molecule for VLDL.
Therapeutic effects
Reduce triglyceride levels
Reduce very low density lipoprotein (VLDL) levels
Modest reduction of low density lipoprotein (LDL) levels
Moderate increase in high density lipoprotein (HDL) levels
Side 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.
Gemfibrozil inhibits the activation of the liver’s Cytochrome P450 system and CYP2C8, reducing hepatic metabolism of many drugs, and prolonging their half lives and duration of action.
Drugs metabolized by the Cytochrome P450 system include:
Many antidepressants
Many antipsychotics
Many antiepileptics
Theophylline and other methylxanthine drugs
Several anesthetic agents
Oral contraceptive pills
Statins
Warfarin
Selexipag
Environmental data
Gemfibrozil has been detected in biosolids (the solids remaining after sewage treatment ) at concentrations up to 2650 ng/g wet weight.

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