Gemfibrozil, sold under the brand name Lopid among others, is a medication used to treat abnormal blood lipid levels.[2] It is generally less preferred than statins.[2][3] Use is recommended together with dietary changes and exercise.[2] It is unclear if it changes the risk of heart disease.[2] It is taken by mouth.[2]
Gemfibrozil was patented in 1968, and came into medical use in 1982.[5] It is available as a generic medication.[3] In 2020, it was the 189th most commonly prescribed medication in the United States, with more than 2million prescriptions.[6][7]
Gemfibrozil should not be given to these patients:[citation needed]
Hepatic dysfunction
Gemfibrozil should be used with caution in these higher risk categories:[citation needed]
Biliary tract disease
Renal dysfunction
Pregnant women
Obese patients
Drug interactions
Anticoagulants: Gemfibrozil potentiates the action of warfarin and indanedione anticoagulants.[citation needed]
Statin drugs: Concomitant administration of fibrates (including gemfibrozil) with statin drugs increases the risk of muscle cramping, myopathy, and rhabdomyolysis.[9]
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:
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.[10]
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.[11]
^"Biosolids". U.S. Environmental Protection Agency. 23 April 2014.
^Doummar J, Aoun M (August 2018). "Assessment of the origin and transport of four selected emerging micropollutants sucralose, Acesulfame-K, gemfibrozil, and iohexol in a karst spring during a multi-event spring response". Journal of Contaminant Hydrology. 215: 11–20. Bibcode:2018JCHyd.215...11D. doi:10.1016/j.jconhyd.2018.06.003. PMID29983209. S2CID51599602.
